Liver Disease

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

People at high risk for nonalcoholic fatty liver disease (NAFLD), such as those with type 2 diabetes or medically complicated obesity, should be screened for advanced fibrosis, says new guidance from the American Association for the Study of Liver Diseases.

The guidance, published online in Hepatology, also reflects recent advances in the diagnosis and management of NAFLD, particularly noninvasive testing, lead author Mary E. Rinella, MD, University of Chicago, told this news organization.

The “biggest change” from the previous guidance, published 5 years ago, is “that we are explicitly recommending that people in high-risk categories get screened in primary care,” she said.

NAFLD is “a silent disease ... you could easily have somebody develop cirrhosis,” Dr. Rinella said. By identifying patients earlier, physicians would be able to “prevent or reduce the number of people turning up decompensated or at an advanced stage,” she added.

The other message that Dr. Rinella wants clinicians to take away from the guidance is that “something can be done” for patients with NAFLD. “It’s very common, and the often-cited reason why patients aren’t referred to specialty care is that there’s ‘nothing that can be done.’ ”

Although there is no U.S. Food and Drug Administration–approved drug for NAFLD, clinicians can still support their patients and suggest lifestyle changes, she added.

The guidelines also are designed to prepare the groundwork for novel drugs in the pipeline, as well as discuss those that are already available for conditions such as obesity and diabetes and that benefit people with liver disease, Dr. Rinella said.
 

Screening and evaluation

The guidance covers all aspects of NAFLD, including the latest developments in understanding of the epidemiology and natural history of the disease, and its molecular and cellular pathogenesis.

The guidance continues to recommend against population-based screening for NAFLD. In addition to the aforementioned screening for advanced fibrosis in high-risk individuals, it calls for a primary risk assessment with FIB-4 to be performed every 1-2 years in patients with pre-diabetes, type 2 diabetes, two or more metabolic risk factors, or imaging evidence of hepatic steatosis.

Patients with nonalcoholic steatohepatitis (NASH) cirrhosis require routine monitoring, as they are at the highest risk for liver-related outcomes, the guidance adds. Those with suspected NASH should be referred for evaluation by a specialist.

In assessments of liver fibrosis in patients, findings such as highly elevated liver stiffness, FIB-4, and enhanced liver fibrosis scores can predict an increased risk for hepatic decompensation and mortality, the authors write.
 

Intervention guidance

Patients with NAFLD who are overweight or obese should be prescribed a reduced calorie diet in a multidisciplinary setting because weight loss “improves hepatic steatosis, NASH, and hepatic fibrosis in a dose-dependent manner,” the guidance states.

Bariatric surgery should be considered in appropriate patients because of its effectiveness in resolving NAFLD and NASH in most patients without cirrhosis, the guidance says. However, in patients with well-compensated NASH cirrhosis, the type, safety, and efficacy of bariatric surgery is not established, so a “careful benefit-risk assessment by a multidisciplinary team of experts that includes a hepatologist” is needed, the authors note.

The guidance discusses alcohol consumption’s role in the progression of fatty liver disease and recommends that intake be assessed on a regular basis in patients with NAFLD. Patients with clinically significant hepatic fibrosis should abstain completely, it adds. Abstinence, particularly for patients with moderate to heavy alcohol intake, may lower the risk of fibrosis progression and hepatic and extrahepatic malignancies, the authors note.

Additionally, drinking at least three cups of coffee, caffeinated or not, per day is “associated with less-advanced liver disease,” they write.

The guidance also sets out key considerations for people with comorbid conditions. It states that patients with NAFLD should be screened for type 2 diabetes and that statins can be safely used for cardiovascular risk reduction “across the disease spectrum, including compensated cirrhosis.”

While noting the lack of approved medications for NAFLD, the guidance states that some drugs prescribed for comorbidities also benefit patients with NASH. These are glucagon-like peptide 1 agonist semaglutide, pioglitazone, and vitamin E supplementation in select patients.

Available data on these same drugs, however, do not show an antifibrotic benefit and haven’t been studied in patients with cirrhosis, the guidance states.

Additionally, metformin, ursodeoxycholic acid, dipeptidyl peptidase-4 inhibitors, silymarin, and statins do not offer meaningful histologic benefit and shouldn’t be used as a treatment for NASH.
 

Help against an ‘evolving epidemic’

The guidance is “timely and long awaited,” Jamile Wakim-Fleming, MD, director of the fatty liver disease program at the Cleveland Clinic, said in an interview. NAFLD is an “evolving epidemic,” she added.

Numerous recent studies have “led to new modalities for diagnosis and therapy, and a better understanding” of the epidemiology and pathophysiology of NAFLD, she said. “More specifically, advancements in noninvasive testing, risk stratifications, and therapeutic modalities are now available and worth disseminating.”

NAFLD’s complexity and the lack of an FDA-approved therapy specifically targeting the liver means that managing the disease “requires expertise in multiple disciplines and knowledge of the latest developments,” Dr. Wakim-Fleming noted.

“This guidance describes preventive and treatment strategies for the metabolic conditions associated with NAFLD and is very useful for physicians in different specialties who treat individuals with these conditions,” she said.

No funding was declared. Dr. Rinella and Dr. Wakim-Fleming have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.


The AGA’s Clinical Practice Update on the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals is available online.

People at high risk for nonalcoholic fatty liver disease (NAFLD), such as those with type 2 diabetes or medically complicated obesity, should be screened for advanced fibrosis, says new guidance from the American Association for the Study of Liver Diseases.

The guidance, published online in Hepatology, also reflects recent advances in the diagnosis and management of NAFLD, particularly noninvasive testing, lead author Mary E. Rinella, MD, University of Chicago, told this news organization.

The “biggest change” from the previous guidance, published 5 years ago, is “that we are explicitly recommending that people in high-risk categories get screened in primary care,” she said.

NAFLD is “a silent disease ... you could easily have somebody develop cirrhosis,” Dr. Rinella said. By identifying patients earlier, physicians would be able to “prevent or reduce the number of people turning up decompensated or at an advanced stage,” she added.

The other message that Dr. Rinella wants clinicians to take away from the guidance is that “something can be done” for patients with NAFLD. “It’s very common, and the often-cited reason why patients aren’t referred to specialty care is that there’s ‘nothing that can be done.’ ”

Although there is no U.S. Food and Drug Administration–approved drug for NAFLD, clinicians can still support their patients and suggest lifestyle changes, she added.

The guidelines also are designed to prepare the groundwork for novel drugs in the pipeline, as well as discuss those that are already available for conditions such as obesity and diabetes and that benefit people with liver disease, Dr. Rinella said.
 

Screening and evaluation

The guidance covers all aspects of NAFLD, including the latest developments in understanding of the epidemiology and natural history of the disease, and its molecular and cellular pathogenesis.

The guidance continues to recommend against population-based screening for NAFLD. In addition to the aforementioned screening for advanced fibrosis in high-risk individuals, it calls for a primary risk assessment with FIB-4 to be performed every 1-2 years in patients with pre-diabetes, type 2 diabetes, two or more metabolic risk factors, or imaging evidence of hepatic steatosis.

Patients with nonalcoholic steatohepatitis (NASH) cirrhosis require routine monitoring, as they are at the highest risk for liver-related outcomes, the guidance adds. Those with suspected NASH should be referred for evaluation by a specialist.

In assessments of liver fibrosis in patients, findings such as highly elevated liver stiffness, FIB-4, and enhanced liver fibrosis scores can predict an increased risk for hepatic decompensation and mortality, the authors write.
 

Intervention guidance

Patients with NAFLD who are overweight or obese should be prescribed a reduced calorie diet in a multidisciplinary setting because weight loss “improves hepatic steatosis, NASH, and hepatic fibrosis in a dose-dependent manner,” the guidance states.

Bariatric surgery should be considered in appropriate patients because of its effectiveness in resolving NAFLD and NASH in most patients without cirrhosis, the guidance says. However, in patients with well-compensated NASH cirrhosis, the type, safety, and efficacy of bariatric surgery is not established, so a “careful benefit-risk assessment by a multidisciplinary team of experts that includes a hepatologist” is needed, the authors note.

The guidance discusses alcohol consumption’s role in the progression of fatty liver disease and recommends that intake be assessed on a regular basis in patients with NAFLD. Patients with clinically significant hepatic fibrosis should abstain completely, it adds. Abstinence, particularly for patients with moderate to heavy alcohol intake, may lower the risk of fibrosis progression and hepatic and extrahepatic malignancies, the authors note.

Additionally, drinking at least three cups of coffee, caffeinated or not, per day is “associated with less-advanced liver disease,” they write.

The guidance also sets out key considerations for people with comorbid conditions. It states that patients with NAFLD should be screened for type 2 diabetes and that statins can be safely used for cardiovascular risk reduction “across the disease spectrum, including compensated cirrhosis.”

While noting the lack of approved medications for NAFLD, the guidance states that some drugs prescribed for comorbidities also benefit patients with NASH. These are glucagon-like peptide 1 agonist semaglutide, pioglitazone, and vitamin E supplementation in select patients.

Available data on these same drugs, however, do not show an antifibrotic benefit and haven’t been studied in patients with cirrhosis, the guidance states.

Additionally, metformin, ursodeoxycholic acid, dipeptidyl peptidase-4 inhibitors, silymarin, and statins do not offer meaningful histologic benefit and shouldn’t be used as a treatment for NASH.
 

Help against an ‘evolving epidemic’

The guidance is “timely and long awaited,” Jamile Wakim-Fleming, MD, director of the fatty liver disease program at the Cleveland Clinic, said in an interview. NAFLD is an “evolving epidemic,” she added.

Numerous recent studies have “led to new modalities for diagnosis and therapy, and a better understanding” of the epidemiology and pathophysiology of NAFLD, she said. “More specifically, advancements in noninvasive testing, risk stratifications, and therapeutic modalities are now available and worth disseminating.”

NAFLD’s complexity and the lack of an FDA-approved therapy specifically targeting the liver means that managing the disease “requires expertise in multiple disciplines and knowledge of the latest developments,” Dr. Wakim-Fleming noted.

“This guidance describes preventive and treatment strategies for the metabolic conditions associated with NAFLD and is very useful for physicians in different specialties who treat individuals with these conditions,” she said.

No funding was declared. Dr. Rinella and Dr. Wakim-Fleming have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.


The AGA’s Clinical Practice Update on the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals is available online.

People at high risk for nonalcoholic fatty liver disease (NAFLD), such as those with type 2 diabetes or medically complicated obesity, should be screened for advanced fibrosis, says new guidance from the American Association for the Study of Liver Diseases.

The guidance, published online in Hepatology, also reflects recent advances in the diagnosis and management of NAFLD, particularly noninvasive testing, lead author Mary E. Rinella, MD, University of Chicago, told this news organization.

The “biggest change” from the previous guidance, published 5 years ago, is “that we are explicitly recommending that people in high-risk categories get screened in primary care,” she said.

NAFLD is “a silent disease ... you could easily have somebody develop cirrhosis,” Dr. Rinella said. By identifying patients earlier, physicians would be able to “prevent or reduce the number of people turning up decompensated or at an advanced stage,” she added.

The other message that Dr. Rinella wants clinicians to take away from the guidance is that “something can be done” for patients with NAFLD. “It’s very common, and the often-cited reason why patients aren’t referred to specialty care is that there’s ‘nothing that can be done.’ ”

Although there is no U.S. Food and Drug Administration–approved drug for NAFLD, clinicians can still support their patients and suggest lifestyle changes, she added.

The guidelines also are designed to prepare the groundwork for novel drugs in the pipeline, as well as discuss those that are already available for conditions such as obesity and diabetes and that benefit people with liver disease, Dr. Rinella said.
 

Screening and evaluation

The guidance covers all aspects of NAFLD, including the latest developments in understanding of the epidemiology and natural history of the disease, and its molecular and cellular pathogenesis.

The guidance continues to recommend against population-based screening for NAFLD. In addition to the aforementioned screening for advanced fibrosis in high-risk individuals, it calls for a primary risk assessment with FIB-4 to be performed every 1-2 years in patients with pre-diabetes, type 2 diabetes, two or more metabolic risk factors, or imaging evidence of hepatic steatosis.

Patients with nonalcoholic steatohepatitis (NASH) cirrhosis require routine monitoring, as they are at the highest risk for liver-related outcomes, the guidance adds. Those with suspected NASH should be referred for evaluation by a specialist.

In assessments of liver fibrosis in patients, findings such as highly elevated liver stiffness, FIB-4, and enhanced liver fibrosis scores can predict an increased risk for hepatic decompensation and mortality, the authors write.
 

Intervention guidance

Patients with NAFLD who are overweight or obese should be prescribed a reduced calorie diet in a multidisciplinary setting because weight loss “improves hepatic steatosis, NASH, and hepatic fibrosis in a dose-dependent manner,” the guidance states.

Bariatric surgery should be considered in appropriate patients because of its effectiveness in resolving NAFLD and NASH in most patients without cirrhosis, the guidance says. However, in patients with well-compensated NASH cirrhosis, the type, safety, and efficacy of bariatric surgery is not established, so a “careful benefit-risk assessment by a multidisciplinary team of experts that includes a hepatologist” is needed, the authors note.

The guidance discusses alcohol consumption’s role in the progression of fatty liver disease and recommends that intake be assessed on a regular basis in patients with NAFLD. Patients with clinically significant hepatic fibrosis should abstain completely, it adds. Abstinence, particularly for patients with moderate to heavy alcohol intake, may lower the risk of fibrosis progression and hepatic and extrahepatic malignancies, the authors note.

Additionally, drinking at least three cups of coffee, caffeinated or not, per day is “associated with less-advanced liver disease,” they write.

The guidance also sets out key considerations for people with comorbid conditions. It states that patients with NAFLD should be screened for type 2 diabetes and that statins can be safely used for cardiovascular risk reduction “across the disease spectrum, including compensated cirrhosis.”

While noting the lack of approved medications for NAFLD, the guidance states that some drugs prescribed for comorbidities also benefit patients with NASH. These are glucagon-like peptide 1 agonist semaglutide, pioglitazone, and vitamin E supplementation in select patients.

Available data on these same drugs, however, do not show an antifibrotic benefit and haven’t been studied in patients with cirrhosis, the guidance states.

Additionally, metformin, ursodeoxycholic acid, dipeptidyl peptidase-4 inhibitors, silymarin, and statins do not offer meaningful histologic benefit and shouldn’t be used as a treatment for NASH.
 

Help against an ‘evolving epidemic’

The guidance is “timely and long awaited,” Jamile Wakim-Fleming, MD, director of the fatty liver disease program at the Cleveland Clinic, said in an interview. NAFLD is an “evolving epidemic,” she added.

Numerous recent studies have “led to new modalities for diagnosis and therapy, and a better understanding” of the epidemiology and pathophysiology of NAFLD, she said. “More specifically, advancements in noninvasive testing, risk stratifications, and therapeutic modalities are now available and worth disseminating.”

NAFLD’s complexity and the lack of an FDA-approved therapy specifically targeting the liver means that managing the disease “requires expertise in multiple disciplines and knowledge of the latest developments,” Dr. Wakim-Fleming noted.

“This guidance describes preventive and treatment strategies for the metabolic conditions associated with NAFLD and is very useful for physicians in different specialties who treat individuals with these conditions,” she said.

No funding was declared. Dr. Rinella and Dr. Wakim-Fleming have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.


The AGA’s Clinical Practice Update on the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals is available online.

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Exercise training is 3.5 times more likely to result in a clinically meaningful response in liver fat, compared with standard clinical care, for patients with nonalcoholic fatty liver disease (NAFLD), according to a new systematic review and meta-analysis.

An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.

“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.

“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.

The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
 

Analyzing studies

Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.

However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.

In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.

The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg². The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.

No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.

Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.

In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.

Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.

For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.

For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.

Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.

An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.

The treatment response was independent of clinically significant body weight loss of more than 5%.

“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
 

Ongoing research

Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.

“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”

Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.

Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.

“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.

Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.

“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Exercise training is 3.5 times more likely to result in a clinically meaningful response in liver fat, compared with standard clinical care, for patients with nonalcoholic fatty liver disease (NAFLD), according to a new systematic review and meta-analysis.

An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.

“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.

“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.

The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
 

Analyzing studies

Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.

However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.

In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.

The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg². The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.

No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.

Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.

In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.

Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.

For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.

For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.

Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.

An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.

The treatment response was independent of clinically significant body weight loss of more than 5%.

“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
 

Ongoing research

Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.

“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”

Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.

Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.

“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.

Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.

“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Exercise training is 3.5 times more likely to result in a clinically meaningful response in liver fat, compared with standard clinical care, for patients with nonalcoholic fatty liver disease (NAFLD), according to a new systematic review and meta-analysis.

An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.

“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.

“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.

The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
 

Analyzing studies

Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.

However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.

In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.

The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg². The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.

No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.

Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.

In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.

Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.

For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.

For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.

Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.

An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.

The treatment response was independent of clinically significant body weight loss of more than 5%.

“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
 

Ongoing research

Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.

“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”

Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.

Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.

“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.

Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.

“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

A version of this article first appeared on Medscape.com.

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

A version of this article first appeared on Medscape.com.

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

A version of this article first appeared on Medscape.com.

For a patient who needs a liver, living donation offers an alternative to staying on a list of more than 10,000 people waiting for a transplant. But what happens when your donor is not a match? To expand the number of living liver donations in the United States, the United Network for Organ Sharing (UNOS) has launched the first national paired liver donation pilot program.

“It’s an exciting time to be caring for patients who need liver transplants,” Benjamin Samstein, MD, chief of liver transplantation at New York–Presbyterian/Weill Cornell Medical Center, New York, said in an interview. He is the principal investigator for the UNOS pilot program. “I do believe it is within our grasp to make sure that nobody dies while waiting for an organ,” he said.

The initiative involves 15 U.S. transplant centers. So far, one recipient-donor pair has enrolled in the program. The pilot program has three main goals: Increase access to living donor transplants; increase access to transplants earlier, when recipients are in better health; and work out how to create and sustain a national program.
 

What is paired donation?

In 2020, 1,095 people died while waiting for a liver transplant, according to a report from the Organ Procurement and Transplant Network (OPTN) – a public-private partnership that includes more than 250 transplant centers and 50 organ procurement organizations across the country.

Most liver transplants involve deceased donors. One way to improve access to lifesaving transplants is through living donation, by which a healthy individual donates part of his or her liver. Someone can participate in nondirected or “altruistic” donation, in which someone donates a liver to someone they don’t know, or they can donate to a specific individual (usually a blood relative or a spouse).

With living liver donation, someone may receive a liver earlier, before getting sick enough to be given priority on the wait-list for deceased donation. Because the recipients are in better health, they may have an easier time recovering from the surgery, Ruthanne Leishman, who manages paired donation programs at UNOS, said in an interview.

In some cases, an individual will want to donate an organ to a specific person, but testing reveals that the two would not be a good match. Paired donation allows incompatible donors and recipients to find matches with other incompatible pairs. Each donor matches with the other pairs’ recipient, so the organs are essentially swapped or exchanged between the two pairs.

“People who want to donate get excited about the fact that they are not just helping their loved one but they’re also helping somebody else,” Ms. Leishman said.

Paired kidney donation programs have been running since 2002, but paired liver donation is relatively new. Since the first U.S. living-donor liver transplant in 1989, the procedure has become safer and is a viable alternative to deceased liver donation. A growing number of living donor programs are popping up at transplant centers across the country.

Still, living-donor liver donation makes up a small percentage of the liver transplants that are performed every year. In 2022, 603 living-donor liver transplants were performed in the United States, compared to 8,925 liver transplants from deceased donors, according to OPTN data. Dr. Samstein estimates a couple dozen paired liver exchanges may have been performed in the United States over the past few years within individual hospital systems. A goal of this pilot program, along with increasing access to liver transplants, is to see whether paired liver donation works on a national level, Ms. Leishman said.
 

Challenges to building a national program

There are several notable differences between living donor kidney transplants and living donor liver transplants. For example, living donor liver transplant is a more complicated surgery and poses greater risk to the donor. According to the OPTN 2020 Annual Report, from 2015 to 2019, the rehospitalization rate for living liver donors was twice that of living kidney donors up to 6 weeks after transplant (4.7% vs. 2.4%). One year post transplant, the cumulative rehospitalization rate was 11.0% for living liver donors and 4.8% for living kidney donors.

The risk of dying because of living donation is also higher for liver donors compared to kidney donors. The National Kidney Association states that the odds of dying during kidney donation are about 3 in 100,000, while estimates for risk of death for living liver donors range from 1 in 500 to 1 in 1,000. But some of these estimates are from 10 or more years ago, and outcomes have likely improved, said Whitney Jackson, MD, medical director of living donor liver transplant at UCHealth University of Colorado Hospital, Aurora. Her program is participating in the UNOS pilot.

More recent data from OPTN provides some idea of risk: Of 3,967 liver donors who donated between March 1, 2008, to Sept. 30, 2022, three deaths were reported within 30 days of transplant. However, the causes of death were not specified and therefore may be unrelated to the surgery. By comparison, of 74,555 kidney donors during that date range, 10 deaths were reported at 30 days post surgery.

In addition to a more complex surgery, surgeons also have a smaller time window in which to transplant a liver than than they do to transplant a kidney. A kidney can remain viable in cold storage for 24-36 hours, and it can be transported via commercial airlines cross country. Livers have to be transplanted within 8-12 hours, according to the OPTN website. For living donation, the graft needs to be transplanted within about 4 hours, Dr. Samstein noted; this poses a logistical challenge for a national organ paired donation program.

“We worked around that with the idea that we would move the donor rather than the organ,” he said. The program will require a donor (and a support person) to travel to the recipient’s transplant center where the surgery will be performed. While 3 of the 15 pilot paired donation transplant centers are in New York City, the other programs are scattered across the country, meaning a donor may have to fly to a different city to undergo surgery.

Including the preoperative evaluation, meeting the surgical team, the surgery itself, and follow-up, the donor could stay for about a month. The program offers up to $10,000 of financial assistance for travel expenses (for both the donor and support person), as well as lost wages and dependent care (for the donor only). Health insurance coverage will also be provided by the pilot program, in partnership with the American Foundation for Donation and Transplant.

The program requires that transplant candidates (the recipients) be at least 12 years old, be on the waiting list for deceased liver donation at one of the pilot’s transplant centers, and have a Model for End-Stage Liver Disease (MELD) score of 25 or less. All potential donors must be 18 years or older and must undergo a medical and psychosocial evaluation. Nondirected donors can register with the program, and they will be paired with a candidate on the liver transplant waiting list at the same transplant center.

The 1-year pilot program is set to begin when the program conducts its first match run – an algorithm will help match pairs who are enrolled in the program. About five to seven enrolled pairs would be ideal for the first match run, a UNOS spokesperson said. It is possible that the 1-year pilot program could run without performing any paired transplants, but that’s unlikely if multiple pairs are enrolled in the system, the spokesperson said. At the time of this story’s publication, the one enrolled pair are a mother and daughter who are registered at the UCHealth Transplant Center in Colorado.
 

Is a national liver paired donor program feasible?

While the UNOS pilot program offers financial assistance for expenses related to liver donation, some transplant surgeons are skeptical about the potential travel component of the pilot program.

The pilot program requires that the donor bring one support person if there is a need to travel for the surgery, but undergoing major abdominal surgery from a transplant team they are not familiar with may be stressful, said Peter Abt, MD, a transplant surgeon at the Hospital of the University of Pennsylvania and the Children’s Hospital of Philadelphia. “That’s a big ask,” he said, “and I’m not sure many potential donors would be up to that.”

John Roberts, MD, a transplant surgeon at the University of California, San Francisco, agreed that the travel component may put additional stress on the donor, but “if it’s the only way for the recipient to get a transplant, then the donor might be motivated,” he added.

Dr. Jackson remains optimistic. “Our experience so far has been that, yes, some people have been hesitant for things like traveling, but a lot of people who seem to be genuinely dedicated to the idea of living donation have been very enthusiastic,” she noted.

Dr. Leishman agreed that the travel aspect appears to one of the greatest barriers to participants entering the program but noted that a goal of the pilot program is to understand better what works - and what doesn’t – when considering a liver paired donation program on a national scale. “[Our] steering committee has put together a really nice framework that they think will work, but they know it’s not perfect. We’re going to have to tweak it along the way,” she said.

More information on the paired liver donation pilot program can be found on the UNOS website.

The sources interviewed for this article reported no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

This article was updated 2/15/23.

For a patient who needs a liver, living donation offers an alternative to staying on a list of more than 10,000 people waiting for a transplant. But what happens when your donor is not a match? To expand the number of living liver donations in the United States, the United Network for Organ Sharing (UNOS) has launched the first national paired liver donation pilot program.

“It’s an exciting time to be caring for patients who need liver transplants,” Benjamin Samstein, MD, chief of liver transplantation at New York–Presbyterian/Weill Cornell Medical Center, New York, said in an interview. He is the principal investigator for the UNOS pilot program. “I do believe it is within our grasp to make sure that nobody dies while waiting for an organ,” he said.

The initiative involves 15 U.S. transplant centers. So far, one recipient-donor pair has enrolled in the program. The pilot program has three main goals: Increase access to living donor transplants; increase access to transplants earlier, when recipients are in better health; and work out how to create and sustain a national program.
 

What is paired donation?

In 2020, 1,095 people died while waiting for a liver transplant, according to a report from the Organ Procurement and Transplant Network (OPTN) – a public-private partnership that includes more than 250 transplant centers and 50 organ procurement organizations across the country.

Most liver transplants involve deceased donors. One way to improve access to lifesaving transplants is through living donation, by which a healthy individual donates part of his or her liver. Someone can participate in nondirected or “altruistic” donation, in which someone donates a liver to someone they don’t know, or they can donate to a specific individual (usually a blood relative or a spouse).

With living liver donation, someone may receive a liver earlier, before getting sick enough to be given priority on the wait-list for deceased donation. Because the recipients are in better health, they may have an easier time recovering from the surgery, Ruthanne Leishman, who manages paired donation programs at UNOS, said in an interview.

In some cases, an individual will want to donate an organ to a specific person, but testing reveals that the two would not be a good match. Paired donation allows incompatible donors and recipients to find matches with other incompatible pairs. Each donor matches with the other pairs’ recipient, so the organs are essentially swapped or exchanged between the two pairs.

“People who want to donate get excited about the fact that they are not just helping their loved one but they’re also helping somebody else,” Ms. Leishman said.

Paired kidney donation programs have been running since 2002, but paired liver donation is relatively new. Since the first U.S. living-donor liver transplant in 1989, the procedure has become safer and is a viable alternative to deceased liver donation. A growing number of living donor programs are popping up at transplant centers across the country.

Still, living-donor liver donation makes up a small percentage of the liver transplants that are performed every year. In 2022, 603 living-donor liver transplants were performed in the United States, compared to 8,925 liver transplants from deceased donors, according to OPTN data. Dr. Samstein estimates a couple dozen paired liver exchanges may have been performed in the United States over the past few years within individual hospital systems. A goal of this pilot program, along with increasing access to liver transplants, is to see whether paired liver donation works on a national level, Ms. Leishman said.
 

Challenges to building a national program

There are several notable differences between living donor kidney transplants and living donor liver transplants. For example, living donor liver transplant is a more complicated surgery and poses greater risk to the donor. According to the OPTN 2020 Annual Report, from 2015 to 2019, the rehospitalization rate for living liver donors was twice that of living kidney donors up to 6 weeks after transplant (4.7% vs. 2.4%). One year post transplant, the cumulative rehospitalization rate was 11.0% for living liver donors and 4.8% for living kidney donors.

The risk of dying because of living donation is also higher for liver donors compared to kidney donors. The National Kidney Association states that the odds of dying during kidney donation are about 3 in 100,000, while estimates for risk of death for living liver donors range from 1 in 500 to 1 in 1,000. But some of these estimates are from 10 or more years ago, and outcomes have likely improved, said Whitney Jackson, MD, medical director of living donor liver transplant at UCHealth University of Colorado Hospital, Aurora. Her program is participating in the UNOS pilot.

More recent data from OPTN provides some idea of risk: Of 3,967 liver donors who donated between March 1, 2008, to Sept. 30, 2022, three deaths were reported within 30 days of transplant. However, the causes of death were not specified and therefore may be unrelated to the surgery. By comparison, of 74,555 kidney donors during that date range, 10 deaths were reported at 30 days post surgery.

In addition to a more complex surgery, surgeons also have a smaller time window in which to transplant a liver than than they do to transplant a kidney. A kidney can remain viable in cold storage for 24-36 hours, and it can be transported via commercial airlines cross country. Livers have to be transplanted within 8-12 hours, according to the OPTN website. For living donation, the graft needs to be transplanted within about 4 hours, Dr. Samstein noted; this poses a logistical challenge for a national organ paired donation program.

“We worked around that with the idea that we would move the donor rather than the organ,” he said. The program will require a donor (and a support person) to travel to the recipient’s transplant center where the surgery will be performed. While 3 of the 15 pilot paired donation transplant centers are in New York City, the other programs are scattered across the country, meaning a donor may have to fly to a different city to undergo surgery.

Including the preoperative evaluation, meeting the surgical team, the surgery itself, and follow-up, the donor could stay for about a month. The program offers up to $10,000 of financial assistance for travel expenses (for both the donor and support person), as well as lost wages and dependent care (for the donor only). Health insurance coverage will also be provided by the pilot program, in partnership with the American Foundation for Donation and Transplant.

The program requires that transplant candidates (the recipients) be at least 12 years old, be on the waiting list for deceased liver donation at one of the pilot’s transplant centers, and have a Model for End-Stage Liver Disease (MELD) score of 25 or less. All potential donors must be 18 years or older and must undergo a medical and psychosocial evaluation. Nondirected donors can register with the program, and they will be paired with a candidate on the liver transplant waiting list at the same transplant center.

The 1-year pilot program is set to begin when the program conducts its first match run – an algorithm will help match pairs who are enrolled in the program. About five to seven enrolled pairs would be ideal for the first match run, a UNOS spokesperson said. It is possible that the 1-year pilot program could run without performing any paired transplants, but that’s unlikely if multiple pairs are enrolled in the system, the spokesperson said. At the time of this story’s publication, the one enrolled pair are a mother and daughter who are registered at the UCHealth Transplant Center in Colorado.
 

Is a national liver paired donor program feasible?

While the UNOS pilot program offers financial assistance for expenses related to liver donation, some transplant surgeons are skeptical about the potential travel component of the pilot program.

The pilot program requires that the donor bring one support person if there is a need to travel for the surgery, but undergoing major abdominal surgery from a transplant team they are not familiar with may be stressful, said Peter Abt, MD, a transplant surgeon at the Hospital of the University of Pennsylvania and the Children’s Hospital of Philadelphia. “That’s a big ask,” he said, “and I’m not sure many potential donors would be up to that.”

John Roberts, MD, a transplant surgeon at the University of California, San Francisco, agreed that the travel component may put additional stress on the donor, but “if it’s the only way for the recipient to get a transplant, then the donor might be motivated,” he added.

Dr. Jackson remains optimistic. “Our experience so far has been that, yes, some people have been hesitant for things like traveling, but a lot of people who seem to be genuinely dedicated to the idea of living donation have been very enthusiastic,” she noted.

Dr. Leishman agreed that the travel aspect appears to one of the greatest barriers to participants entering the program but noted that a goal of the pilot program is to understand better what works - and what doesn’t – when considering a liver paired donation program on a national scale. “[Our] steering committee has put together a really nice framework that they think will work, but they know it’s not perfect. We’re going to have to tweak it along the way,” she said.

More information on the paired liver donation pilot program can be found on the UNOS website.

The sources interviewed for this article reported no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

This article was updated 2/15/23.

For a patient who needs a liver, living donation offers an alternative to staying on a list of more than 10,000 people waiting for a transplant. But what happens when your donor is not a match? To expand the number of living liver donations in the United States, the United Network for Organ Sharing (UNOS) has launched the first national paired liver donation pilot program.

“It’s an exciting time to be caring for patients who need liver transplants,” Benjamin Samstein, MD, chief of liver transplantation at New York–Presbyterian/Weill Cornell Medical Center, New York, said in an interview. He is the principal investigator for the UNOS pilot program. “I do believe it is within our grasp to make sure that nobody dies while waiting for an organ,” he said.

The initiative involves 15 U.S. transplant centers. So far, one recipient-donor pair has enrolled in the program. The pilot program has three main goals: Increase access to living donor transplants; increase access to transplants earlier, when recipients are in better health; and work out how to create and sustain a national program.
 

What is paired donation?

In 2020, 1,095 people died while waiting for a liver transplant, according to a report from the Organ Procurement and Transplant Network (OPTN) – a public-private partnership that includes more than 250 transplant centers and 50 organ procurement organizations across the country.

Most liver transplants involve deceased donors. One way to improve access to lifesaving transplants is through living donation, by which a healthy individual donates part of his or her liver. Someone can participate in nondirected or “altruistic” donation, in which someone donates a liver to someone they don’t know, or they can donate to a specific individual (usually a blood relative or a spouse).

With living liver donation, someone may receive a liver earlier, before getting sick enough to be given priority on the wait-list for deceased donation. Because the recipients are in better health, they may have an easier time recovering from the surgery, Ruthanne Leishman, who manages paired donation programs at UNOS, said in an interview.

In some cases, an individual will want to donate an organ to a specific person, but testing reveals that the two would not be a good match. Paired donation allows incompatible donors and recipients to find matches with other incompatible pairs. Each donor matches with the other pairs’ recipient, so the organs are essentially swapped or exchanged between the two pairs.

“People who want to donate get excited about the fact that they are not just helping their loved one but they’re also helping somebody else,” Ms. Leishman said.

Paired kidney donation programs have been running since 2002, but paired liver donation is relatively new. Since the first U.S. living-donor liver transplant in 1989, the procedure has become safer and is a viable alternative to deceased liver donation. A growing number of living donor programs are popping up at transplant centers across the country.

Still, living-donor liver donation makes up a small percentage of the liver transplants that are performed every year. In 2022, 603 living-donor liver transplants were performed in the United States, compared to 8,925 liver transplants from deceased donors, according to OPTN data. Dr. Samstein estimates a couple dozen paired liver exchanges may have been performed in the United States over the past few years within individual hospital systems. A goal of this pilot program, along with increasing access to liver transplants, is to see whether paired liver donation works on a national level, Ms. Leishman said.
 

Challenges to building a national program

There are several notable differences between living donor kidney transplants and living donor liver transplants. For example, living donor liver transplant is a more complicated surgery and poses greater risk to the donor. According to the OPTN 2020 Annual Report, from 2015 to 2019, the rehospitalization rate for living liver donors was twice that of living kidney donors up to 6 weeks after transplant (4.7% vs. 2.4%). One year post transplant, the cumulative rehospitalization rate was 11.0% for living liver donors and 4.8% for living kidney donors.

The risk of dying because of living donation is also higher for liver donors compared to kidney donors. The National Kidney Association states that the odds of dying during kidney donation are about 3 in 100,000, while estimates for risk of death for living liver donors range from 1 in 500 to 1 in 1,000. But some of these estimates are from 10 or more years ago, and outcomes have likely improved, said Whitney Jackson, MD, medical director of living donor liver transplant at UCHealth University of Colorado Hospital, Aurora. Her program is participating in the UNOS pilot.

More recent data from OPTN provides some idea of risk: Of 3,967 liver donors who donated between March 1, 2008, to Sept. 30, 2022, three deaths were reported within 30 days of transplant. However, the causes of death were not specified and therefore may be unrelated to the surgery. By comparison, of 74,555 kidney donors during that date range, 10 deaths were reported at 30 days post surgery.

In addition to a more complex surgery, surgeons also have a smaller time window in which to transplant a liver than than they do to transplant a kidney. A kidney can remain viable in cold storage for 24-36 hours, and it can be transported via commercial airlines cross country. Livers have to be transplanted within 8-12 hours, according to the OPTN website. For living donation, the graft needs to be transplanted within about 4 hours, Dr. Samstein noted; this poses a logistical challenge for a national organ paired donation program.

“We worked around that with the idea that we would move the donor rather than the organ,” he said. The program will require a donor (and a support person) to travel to the recipient’s transplant center where the surgery will be performed. While 3 of the 15 pilot paired donation transplant centers are in New York City, the other programs are scattered across the country, meaning a donor may have to fly to a different city to undergo surgery.

Including the preoperative evaluation, meeting the surgical team, the surgery itself, and follow-up, the donor could stay for about a month. The program offers up to $10,000 of financial assistance for travel expenses (for both the donor and support person), as well as lost wages and dependent care (for the donor only). Health insurance coverage will also be provided by the pilot program, in partnership with the American Foundation for Donation and Transplant.

The program requires that transplant candidates (the recipients) be at least 12 years old, be on the waiting list for deceased liver donation at one of the pilot’s transplant centers, and have a Model for End-Stage Liver Disease (MELD) score of 25 or less. All potential donors must be 18 years or older and must undergo a medical and psychosocial evaluation. Nondirected donors can register with the program, and they will be paired with a candidate on the liver transplant waiting list at the same transplant center.

The 1-year pilot program is set to begin when the program conducts its first match run – an algorithm will help match pairs who are enrolled in the program. About five to seven enrolled pairs would be ideal for the first match run, a UNOS spokesperson said. It is possible that the 1-year pilot program could run without performing any paired transplants, but that’s unlikely if multiple pairs are enrolled in the system, the spokesperson said. At the time of this story’s publication, the one enrolled pair are a mother and daughter who are registered at the UCHealth Transplant Center in Colorado.
 

Is a national liver paired donor program feasible?

While the UNOS pilot program offers financial assistance for expenses related to liver donation, some transplant surgeons are skeptical about the potential travel component of the pilot program.

The pilot program requires that the donor bring one support person if there is a need to travel for the surgery, but undergoing major abdominal surgery from a transplant team they are not familiar with may be stressful, said Peter Abt, MD, a transplant surgeon at the Hospital of the University of Pennsylvania and the Children’s Hospital of Philadelphia. “That’s a big ask,” he said, “and I’m not sure many potential donors would be up to that.”

John Roberts, MD, a transplant surgeon at the University of California, San Francisco, agreed that the travel component may put additional stress on the donor, but “if it’s the only way for the recipient to get a transplant, then the donor might be motivated,” he added.

Dr. Jackson remains optimistic. “Our experience so far has been that, yes, some people have been hesitant for things like traveling, but a lot of people who seem to be genuinely dedicated to the idea of living donation have been very enthusiastic,” she noted.

Dr. Leishman agreed that the travel aspect appears to one of the greatest barriers to participants entering the program but noted that a goal of the pilot program is to understand better what works - and what doesn’t – when considering a liver paired donation program on a national scale. “[Our] steering committee has put together a really nice framework that they think will work, but they know it’s not perfect. We’re going to have to tweak it along the way,” she said.

More information on the paired liver donation pilot program can be found on the UNOS website.

The sources interviewed for this article reported no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

This article was updated 2/15/23.

A noninvasive test for liver disease may be a useful, low-cost screening tool to select asymptomatic candidates for a detailed examination of heart failure with preserved ejection fraction (HFpEF), say authors of a report published in Gastro Hep Advances.

The fibrosis-4 (FIB-4) index was a significant predictor of high HFpEF risk, wrote Chisato Okamoto, MD, of the department of medical biochemistry at Osaka University Graduate School of Medicine and the National Cerebral and Cardiovascular Center in Japan, and colleagues.

“Recognition of heart failure with preserved ejection fraction at an early stage in mass screening is desirable, but difficult to achieve,” the authors wrote. “The FIB-4 index is calculated using only four parameters that are routinely evaluated in general health check-up programs.”

HFpEF is an emerging disease in recent years with a poor prognosis, they wrote. Early diagnosis can be challenging for several reasons, particularly because HFpEF patients are often asymptomatic until late in the disease process and have normal left ventricular filling pressures at rest. By using a tool to select probable cases from subclinical participants in a health check-up program, clinicians can refer patients for a diastolic stress test, which is considered the gold standard for diagnosing HFpEF.

Previous studies have found that the FIB-4 index, a noninvasive tool to estimate liver stiffness and fibrosis, is associated with a higher risk of major adverse cardiovascular events (MACE) in patients with HFpEF. In addition, patients with nonalcoholic fatty liver disease (NAFLD) have a twofold higher prevalence of HFpEF than the general population.

Dr. Okamoto and colleagues examined the association between the FIB-4 index and HFpEF risk based on the Heart Failure Association’s diagnostic algorithm for HFpEF in patients with breathlessness (HFA-PEFF). The researchers looked at the prognostic impact of the FIB-4 index in 710 patients who participated in a health check-up program in the rural community of Arita-cho, Japan, between 2006 and 2007. They excluded participants with a history of cardiovascular disease or reduced left ventricular systolic function (LVEF < 50%). Researchers calculated the FIB-4 index and HFA-PEFF score for all participants.

First, using the HFA-PEFF scores, the researchers sorted participants into five groups by HFpEF risk: 215 (30%) with zero points, 100 (14%) with 1 point, 171 (24%) with 2 points, 163 (23%) with 3 points, and 61 (9%) with 4-6 points. Participants in the high-risk group (scores 4-6) were older, mostly men, and had higher blood pressure, alcohol intake, hypertension, dyslipidemia, and liver disease. The higher the HFpEF risk group, the higher the rates of all-cause mortality, hospitalization for heart failure, and MACE.

Overall, the FIB-4 index was correlated with the HFpEF risk groups and showed a stepwise increase across the groups, with .94 for the low-risk group, 1.45 for the intermediate-risk group, and 1.99 for the high-risk group, the authors wrote. The FIB-4 index also correlated with markers associated with components of the HFA-PEFF scoring system.

Using multivariate logistic regression analysis, the FIB-4 index was associated with a high HFpEF risk, and an increase in FIB-4 was associated with increased odds of high HFpEF risk. The association remained significant across four separate models that accounted for risk factors associated with lifestyle-related diseases, blood parameters associated with liver disease, and chronic conditions such as hypertension, dyslipidemia, diabetes mellitus, and liver disease.

In additional area under the curve (AUC) analyses, the FIB-4 index was a significant predictor of high HFpEF risk. At cutoff values typically used for advanced liver fibrosis in NAFLD, a FIB-4 cutoff of 1.3 or less had a sensitivity of 85.2%, while a FIB-4 cutoff of 2.67 or higher had a specificity of 94.8%. At alternate cutoff values typically used for patients with HIV/hepatitis C virus infection, a FIB-4 cutoff of less than 1.45 had a sensitivity of 75.4%, while a FIB-4 cutoff of greater than 3.25 had a specificity of 98%.

Using cutoffs of 1.3 and 2.67, a higher FIB-4 was associated with higher rates of clinical events and MACE, as well as a higher HFpEF risk. Using the alternate cutoffs of 1.45 and 3.25, prognostic stratification of clinical events and MACE was also possible.

When all variables were included in the multivariate model, the FIB-4 index remained a significant prognostic predictor. The FIB-4 index stratified clinical prognosis was also an independent predictor of all-cause mortality and hospitalization for heart failure.

Although additional studies are needed to reveal the interaction between liver and heart function, the study authors wrote, the findings provide valuable insights that can help discover the cardiohepatic interaction to reduce the development of HFpEF.

“Since it can be easily, quickly, and inexpensively measured, routine or repeated measurements of the FIB-4 index could help in selecting preferred candidates for detailed examination of HFpEF risk, which may improve clinical outcomes by diagnosing HFpEF at an early stage,” they wrote.

The study was supported by grants from the Osaka Medical Research Foundation for Intractable Disease, the Japan Arteriosclerosis Prevention Fund, the Japan Society for the Promotion of Science, and the Japan Heart Foundation. The authors disclosed no conflicts.

A noninvasive test for liver disease may be a useful, low-cost screening tool to select asymptomatic candidates for a detailed examination of heart failure with preserved ejection fraction (HFpEF), say authors of a report published in Gastro Hep Advances.

The fibrosis-4 (FIB-4) index was a significant predictor of high HFpEF risk, wrote Chisato Okamoto, MD, of the department of medical biochemistry at Osaka University Graduate School of Medicine and the National Cerebral and Cardiovascular Center in Japan, and colleagues.

“Recognition of heart failure with preserved ejection fraction at an early stage in mass screening is desirable, but difficult to achieve,” the authors wrote. “The FIB-4 index is calculated using only four parameters that are routinely evaluated in general health check-up programs.”

HFpEF is an emerging disease in recent years with a poor prognosis, they wrote. Early diagnosis can be challenging for several reasons, particularly because HFpEF patients are often asymptomatic until late in the disease process and have normal left ventricular filling pressures at rest. By using a tool to select probable cases from subclinical participants in a health check-up program, clinicians can refer patients for a diastolic stress test, which is considered the gold standard for diagnosing HFpEF.

Previous studies have found that the FIB-4 index, a noninvasive tool to estimate liver stiffness and fibrosis, is associated with a higher risk of major adverse cardiovascular events (MACE) in patients with HFpEF. In addition, patients with nonalcoholic fatty liver disease (NAFLD) have a twofold higher prevalence of HFpEF than the general population.

Dr. Okamoto and colleagues examined the association between the FIB-4 index and HFpEF risk based on the Heart Failure Association’s diagnostic algorithm for HFpEF in patients with breathlessness (HFA-PEFF). The researchers looked at the prognostic impact of the FIB-4 index in 710 patients who participated in a health check-up program in the rural community of Arita-cho, Japan, between 2006 and 2007. They excluded participants with a history of cardiovascular disease or reduced left ventricular systolic function (LVEF < 50%). Researchers calculated the FIB-4 index and HFA-PEFF score for all participants.

First, using the HFA-PEFF scores, the researchers sorted participants into five groups by HFpEF risk: 215 (30%) with zero points, 100 (14%) with 1 point, 171 (24%) with 2 points, 163 (23%) with 3 points, and 61 (9%) with 4-6 points. Participants in the high-risk group (scores 4-6) were older, mostly men, and had higher blood pressure, alcohol intake, hypertension, dyslipidemia, and liver disease. The higher the HFpEF risk group, the higher the rates of all-cause mortality, hospitalization for heart failure, and MACE.

Overall, the FIB-4 index was correlated with the HFpEF risk groups and showed a stepwise increase across the groups, with .94 for the low-risk group, 1.45 for the intermediate-risk group, and 1.99 for the high-risk group, the authors wrote. The FIB-4 index also correlated with markers associated with components of the HFA-PEFF scoring system.

Using multivariate logistic regression analysis, the FIB-4 index was associated with a high HFpEF risk, and an increase in FIB-4 was associated with increased odds of high HFpEF risk. The association remained significant across four separate models that accounted for risk factors associated with lifestyle-related diseases, blood parameters associated with liver disease, and chronic conditions such as hypertension, dyslipidemia, diabetes mellitus, and liver disease.

In additional area under the curve (AUC) analyses, the FIB-4 index was a significant predictor of high HFpEF risk. At cutoff values typically used for advanced liver fibrosis in NAFLD, a FIB-4 cutoff of 1.3 or less had a sensitivity of 85.2%, while a FIB-4 cutoff of 2.67 or higher had a specificity of 94.8%. At alternate cutoff values typically used for patients with HIV/hepatitis C virus infection, a FIB-4 cutoff of less than 1.45 had a sensitivity of 75.4%, while a FIB-4 cutoff of greater than 3.25 had a specificity of 98%.

Using cutoffs of 1.3 and 2.67, a higher FIB-4 was associated with higher rates of clinical events and MACE, as well as a higher HFpEF risk. Using the alternate cutoffs of 1.45 and 3.25, prognostic stratification of clinical events and MACE was also possible.

When all variables were included in the multivariate model, the FIB-4 index remained a significant prognostic predictor. The FIB-4 index stratified clinical prognosis was also an independent predictor of all-cause mortality and hospitalization for heart failure.

Although additional studies are needed to reveal the interaction between liver and heart function, the study authors wrote, the findings provide valuable insights that can help discover the cardiohepatic interaction to reduce the development of HFpEF.

“Since it can be easily, quickly, and inexpensively measured, routine or repeated measurements of the FIB-4 index could help in selecting preferred candidates for detailed examination of HFpEF risk, which may improve clinical outcomes by diagnosing HFpEF at an early stage,” they wrote.

The study was supported by grants from the Osaka Medical Research Foundation for Intractable Disease, the Japan Arteriosclerosis Prevention Fund, the Japan Society for the Promotion of Science, and the Japan Heart Foundation. The authors disclosed no conflicts.

A noninvasive test for liver disease may be a useful, low-cost screening tool to select asymptomatic candidates for a detailed examination of heart failure with preserved ejection fraction (HFpEF), say authors of a report published in Gastro Hep Advances.

The fibrosis-4 (FIB-4) index was a significant predictor of high HFpEF risk, wrote Chisato Okamoto, MD, of the department of medical biochemistry at Osaka University Graduate School of Medicine and the National Cerebral and Cardiovascular Center in Japan, and colleagues.

“Recognition of heart failure with preserved ejection fraction at an early stage in mass screening is desirable, but difficult to achieve,” the authors wrote. “The FIB-4 index is calculated using only four parameters that are routinely evaluated in general health check-up programs.”

HFpEF is an emerging disease in recent years with a poor prognosis, they wrote. Early diagnosis can be challenging for several reasons, particularly because HFpEF patients are often asymptomatic until late in the disease process and have normal left ventricular filling pressures at rest. By using a tool to select probable cases from subclinical participants in a health check-up program, clinicians can refer patients for a diastolic stress test, which is considered the gold standard for diagnosing HFpEF.

Previous studies have found that the FIB-4 index, a noninvasive tool to estimate liver stiffness and fibrosis, is associated with a higher risk of major adverse cardiovascular events (MACE) in patients with HFpEF. In addition, patients with nonalcoholic fatty liver disease (NAFLD) have a twofold higher prevalence of HFpEF than the general population.

Dr. Okamoto and colleagues examined the association between the FIB-4 index and HFpEF risk based on the Heart Failure Association’s diagnostic algorithm for HFpEF in patients with breathlessness (HFA-PEFF). The researchers looked at the prognostic impact of the FIB-4 index in 710 patients who participated in a health check-up program in the rural community of Arita-cho, Japan, between 2006 and 2007. They excluded participants with a history of cardiovascular disease or reduced left ventricular systolic function (LVEF < 50%). Researchers calculated the FIB-4 index and HFA-PEFF score for all participants.

First, using the HFA-PEFF scores, the researchers sorted participants into five groups by HFpEF risk: 215 (30%) with zero points, 100 (14%) with 1 point, 171 (24%) with 2 points, 163 (23%) with 3 points, and 61 (9%) with 4-6 points. Participants in the high-risk group (scores 4-6) were older, mostly men, and had higher blood pressure, alcohol intake, hypertension, dyslipidemia, and liver disease. The higher the HFpEF risk group, the higher the rates of all-cause mortality, hospitalization for heart failure, and MACE.

Overall, the FIB-4 index was correlated with the HFpEF risk groups and showed a stepwise increase across the groups, with .94 for the low-risk group, 1.45 for the intermediate-risk group, and 1.99 for the high-risk group, the authors wrote. The FIB-4 index also correlated with markers associated with components of the HFA-PEFF scoring system.

Using multivariate logistic regression analysis, the FIB-4 index was associated with a high HFpEF risk, and an increase in FIB-4 was associated with increased odds of high HFpEF risk. The association remained significant across four separate models that accounted for risk factors associated with lifestyle-related diseases, blood parameters associated with liver disease, and chronic conditions such as hypertension, dyslipidemia, diabetes mellitus, and liver disease.

In additional area under the curve (AUC) analyses, the FIB-4 index was a significant predictor of high HFpEF risk. At cutoff values typically used for advanced liver fibrosis in NAFLD, a FIB-4 cutoff of 1.3 or less had a sensitivity of 85.2%, while a FIB-4 cutoff of 2.67 or higher had a specificity of 94.8%. At alternate cutoff values typically used for patients with HIV/hepatitis C virus infection, a FIB-4 cutoff of less than 1.45 had a sensitivity of 75.4%, while a FIB-4 cutoff of greater than 3.25 had a specificity of 98%.

Using cutoffs of 1.3 and 2.67, a higher FIB-4 was associated with higher rates of clinical events and MACE, as well as a higher HFpEF risk. Using the alternate cutoffs of 1.45 and 3.25, prognostic stratification of clinical events and MACE was also possible.

When all variables were included in the multivariate model, the FIB-4 index remained a significant prognostic predictor. The FIB-4 index stratified clinical prognosis was also an independent predictor of all-cause mortality and hospitalization for heart failure.

Although additional studies are needed to reveal the interaction between liver and heart function, the study authors wrote, the findings provide valuable insights that can help discover the cardiohepatic interaction to reduce the development of HFpEF.

“Since it can be easily, quickly, and inexpensively measured, routine or repeated measurements of the FIB-4 index could help in selecting preferred candidates for detailed examination of HFpEF risk, which may improve clinical outcomes by diagnosing HFpEF at an early stage,” they wrote.

The study was supported by grants from the Osaka Medical Research Foundation for Intractable Disease, the Japan Arteriosclerosis Prevention Fund, the Japan Society for the Promotion of Science, and the Japan Heart Foundation. The authors disclosed no conflicts.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

The FibroScan-aspartate aminotransferase (FAST) score shows high sensitivity and specificity for noninvasive identification of patients with fibrotic nonalcoholic steatohepatitis (NASH), according to a new systematic review and meta-analysis.

The FAST score had an overall sensitivity of 89% and an overall specificity of 89% with a defined rule-out cutoff of .35 or lower and rule-in cutoff of .67 or higher, respectively, Federico Ravaioli, MD, PhD, a gastroenterologist at the University of Modena & Reggio Emilia in Italy, and colleagues, wrote in Gut.

“These results could be used in clinical screening studies to efficiently identify patients at risk of progressive NASH, who should be referred for a conclusive liver biopsy, and who might benefit from treatment with emerging pharmacotherapies,” the authors wrote.

The research team analyzed 12 observational studies with 5,835 participants with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) between February 2020 and April 2022. They included articles that reported data for the calculation of sensitivity and specificity of the FAST score for identifying adult patients with fibrotic NASH based on a defined rule-out cutoff of .35 or lower and rule-in cutoff of .67 or higher. Fibrotic NASH was defined as patients with NASH plus a NAFLD activity score of 4 or greater and fibrosis stage 2 or higher.

The pooled prevalence of fibrotic NASH was 28%. The mean age of participants ranged from 40 to 60, and the proportion of men ranged from 23% to 91%. The mean body mass index ranged from 23 kg/m² to 41 kg/m², with a prevalence of obesity ranging from 23% to 100% and preexisting type 2 diabetes ranging from 18% to 60%. Nine studies included patients with biopsy-proven NAFLD from tertiary care liver centers, and three studies included patients from bariatric clinics or bariatric surgery centers with available liver biopsy data.

Fibrotic NASH was ruled out in 2,723 patients (45.5%) by a FAST score of .35 or lower and ruled in 1,287 patients (21.5%) by a FAST score of .67 or higher. In addition, 1,979 patients (33%) had a FAST score in the so-called “grey” intermediate zone.

Overall, the FAST score pooled sensitivity was 89%, and the pooled specificity was 89%. By the rule-out cutoff of .35, the sensitivity was 89% and the specificity was 56%. By the rule-in cutoff of .67, the sensitivity was 46% and the specificity was 89%.

At an expected prevalence of fibrotic NASH of 30%, the negative predictive value of the .35 cutoff was 92%, and the positive predictive value of the .67 cutoff was 65%. Across the included studies, the negative predictive value ranged from 77% to 98%, and the positive predictive value ranged from 32% to 87%.

For the rule-in cutoff of .67, at a pretest probability of 10%, 20%, 26.3%, and 30%, there was an increasing likelihood of detecting fibrotic NASH by FAST score at 32%, 52%, 60%, and 65%, respectively. For the rule-out cutoff of .35, at the same pretest probability levels, the likelihood of someone not having fibrotic NASH and not being detected by FAST score was 2%, 5%, 7%, and 8%, respectively.

In subgroup analyses, the sensitivity of the rule-out cutoff was significantly affected by the study design. In addition, age and BMI above the median both affected pooled sensitivity but not pooled specificity. On the other hand, the rule-in cutoff was significantly affected by study design, BMI above the median, and presence of preexisting type 2 diabetes above the median.

“Today, we stand on the cusp of a revolutionary time to treat NASH. This is due in part to the fact that many exciting, novel precision metabolic treatments are in the pipeline to combat this disease,” said Brian DeBosch, MD, PhD, associate professor of cell biology and physiology at the Washington University in St. Louis, who was not involved with this study.

The FibroScan-aspartate aminotransferase (FAST) score shows high sensitivity and specificity for noninvasive identification of patients with fibrotic nonalcoholic steatohepatitis (NASH), according to a new systematic review and meta-analysis.

The FAST score had an overall sensitivity of 89% and an overall specificity of 89% with a defined rule-out cutoff of .35 or lower and rule-in cutoff of .67 or higher, respectively, Federico Ravaioli, MD, PhD, a gastroenterologist at the University of Modena & Reggio Emilia in Italy, and colleagues, wrote in Gut.

“These results could be used in clinical screening studies to efficiently identify patients at risk of progressive NASH, who should be referred for a conclusive liver biopsy, and who might benefit from treatment with emerging pharmacotherapies,” the authors wrote.

The research team analyzed 12 observational studies with 5,835 participants with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) between February 2020 and April 2022. They included articles that reported data for the calculation of sensitivity and specificity of the FAST score for identifying adult patients with fibrotic NASH based on a defined rule-out cutoff of .35 or lower and rule-in cutoff of .67 or higher. Fibrotic NASH was defined as patients with NASH plus a NAFLD activity score of 4 or greater and fibrosis stage 2 or higher.

The pooled prevalence of fibrotic NASH was 28%. The mean age of participants ranged from 40 to 60, and the proportion of men ranged from 23% to 91%. The mean body mass index ranged from 23 kg/m² to 41 kg/m², with a prevalence of obesity ranging from 23% to 100% and preexisting type 2 diabetes ranging from 18% to 60%. Nine studies included patients with biopsy-proven NAFLD from tertiary care liver centers, and three studies included patients from bariatric clinics or bariatric surgery centers with available liver biopsy data.

Fibrotic NASH was ruled out in 2,723 patients (45.5%) by a FAST score of .35 or lower and ruled in 1,287 patients (21.5%) by a FAST score of .67 or higher. In addition, 1,979 patients (33%) had a FAST score in the so-called “grey” intermediate zone.

Overall, the FAST score pooled sensitivity was 89%, and the pooled specificity was 89%. By the rule-out cutoff of .35, the sensitivity was 89% and the specificity was 56%. By the rule-in cutoff of .67, the sensitivity was 46% and the specificity was 89%.

At an expected prevalence of fibrotic NASH of 30%, the negative predictive value of the .35 cutoff was 92%, and the positive predictive value of the .67 cutoff was 65%. Across the included studies, the negative predictive value ranged from 77% to 98%, and the positive predictive value ranged from 32% to 87%.

For the rule-in cutoff of .67, at a pretest probability of 10%, 20%, 26.3%, and 30%, there was an increasing likelihood of detecting fibrotic NASH by FAST score at 32%, 52%, 60%, and 65%, respectively. For the rule-out cutoff of .35, at the same pretest probability levels, the likelihood of someone not having fibrotic NASH and not being detected by FAST score was 2%, 5%, 7%, and 8%, respectively.

In subgroup analyses, the sensitivity of the rule-out cutoff was significantly affected by the study design. In addition, age and BMI above the median both affected pooled sensitivity but not pooled specificity. On the other hand, the rule-in cutoff was significantly affected by study design, BMI above the median, and presence of preexisting type 2 diabetes above the median.

“Today, we stand on the cusp of a revolutionary time to treat NASH. This is due in part to the fact that many exciting, novel precision metabolic treatments are in the pipeline to combat this disease,” said Brian DeBosch, MD, PhD, associate professor of cell biology and physiology at the Washington University in St. Louis, who was not involved with this study.

The FibroScan-aspartate aminotransferase (FAST) score shows high sensitivity and specificity for noninvasive identification of patients with fibrotic nonalcoholic steatohepatitis (NASH), according to a new systematic review and meta-analysis.

The FAST score had an overall sensitivity of 89% and an overall specificity of 89% with a defined rule-out cutoff of .35 or lower and rule-in cutoff of .67 or higher, respectively, Federico Ravaioli, MD, PhD, a gastroenterologist at the University of Modena & Reggio Emilia in Italy, and colleagues, wrote in Gut.

“These results could be used in clinical screening studies to efficiently identify patients at risk of progressive NASH, who should be referred for a conclusive liver biopsy, and who might benefit from treatment with emerging pharmacotherapies,” the authors wrote.

The research team analyzed 12 observational studies with 5,835 participants with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) between February 2020 and April 2022. They included articles that reported data for the calculation of sensitivity and specificity of the FAST score for identifying adult patients with fibrotic NASH based on a defined rule-out cutoff of .35 or lower and rule-in cutoff of .67 or higher. Fibrotic NASH was defined as patients with NASH plus a NAFLD activity score of 4 or greater and fibrosis stage 2 or higher.

The pooled prevalence of fibrotic NASH was 28%. The mean age of participants ranged from 40 to 60, and the proportion of men ranged from 23% to 91%. The mean body mass index ranged from 23 kg/m² to 41 kg/m², with a prevalence of obesity ranging from 23% to 100% and preexisting type 2 diabetes ranging from 18% to 60%. Nine studies included patients with biopsy-proven NAFLD from tertiary care liver centers, and three studies included patients from bariatric clinics or bariatric surgery centers with available liver biopsy data.

Fibrotic NASH was ruled out in 2,723 patients (45.5%) by a FAST score of .35 or lower and ruled in 1,287 patients (21.5%) by a FAST score of .67 or higher. In addition, 1,979 patients (33%) had a FAST score in the so-called “grey” intermediate zone.

Overall, the FAST score pooled sensitivity was 89%, and the pooled specificity was 89%. By the rule-out cutoff of .35, the sensitivity was 89% and the specificity was 56%. By the rule-in cutoff of .67, the sensitivity was 46% and the specificity was 89%.

At an expected prevalence of fibrotic NASH of 30%, the negative predictive value of the .35 cutoff was 92%, and the positive predictive value of the .67 cutoff was 65%. Across the included studies, the negative predictive value ranged from 77% to 98%, and the positive predictive value ranged from 32% to 87%.

For the rule-in cutoff of .67, at a pretest probability of 10%, 20%, 26.3%, and 30%, there was an increasing likelihood of detecting fibrotic NASH by FAST score at 32%, 52%, 60%, and 65%, respectively. For the rule-out cutoff of .35, at the same pretest probability levels, the likelihood of someone not having fibrotic NASH and not being detected by FAST score was 2%, 5%, 7%, and 8%, respectively.

In subgroup analyses, the sensitivity of the rule-out cutoff was significantly affected by the study design. In addition, age and BMI above the median both affected pooled sensitivity but not pooled specificity. On the other hand, the rule-in cutoff was significantly affected by study design, BMI above the median, and presence of preexisting type 2 diabetes above the median.

“Today, we stand on the cusp of a revolutionary time to treat NASH. This is due in part to the fact that many exciting, novel precision metabolic treatments are in the pipeline to combat this disease,” said Brian DeBosch, MD, PhD, associate professor of cell biology and physiology at the Washington University in St. Louis, who was not involved with this study.

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.