TBD Meeting (3224-21)

A home-based tunneled peritoneal catheter (PeCa) drainage system provided significant relief for patients with refractory ascites who were not candidates for transjugular intrahepatic portosystemic shunt (TIPS).

For these patients, the current standard of care is repeated large volume paracentesis, but this can require frequent hospital trips that can be costly and onerous.

The PeCa system consists of one part that lays in the peritoneal cavity, then a tunnel through subcutaneous tissue and an external port where the patient can connect drainage bags. It has been tested and found to provide relief for patients with malignant ascites, but there is little data available for patients with cirrhosis, according to Tammo Lambert Tergast, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Tergast is a resident in the department of gastroenterology, hepatology, and endocrinology at Hannover (Germany) Medical School.

“Patients with refractory ascites have a very high risk for rehospitalization, AKI [acute kidney injury], and death. Our data indicate that PeCa could be a valuable new treatment option for patients with refractory ascites and contraindication for TIPS. However, the risk for hyponatremia and AKI has to be considered and further explored,” said Dr. Tergast during his presentation.

The researchers retrospectively analyzed outcomes in 152 patients with refractory ascites who received a PeCa implant and 71 patients who received standard of care (SOC), which included repeated large volume paracentesis and albumin. The median explant-free survival was 74 days, and just under 50% were explant free at 90 days.

52 patients had the PeCa system removed: 54% because of an infection, 15% because of liver transplant, 12% because of dysfunction, and 10% because of accidental removal.

Factors associated with 90-day survival included PeCa (hazard ratio, 0.52; P = .05) and each point of Model for End-Stage Liver Disease (MELD) score (HR, 1.16; P = .001). There was a trend toward a higher incidence of hyponatremia in the PeCa group (P = .09).

Hospitalizations were more common in the PeCa group (P = .035), but there was no significant difference in mortality between the two groups. Reasons for hospitalization included spontaneous bacterial peritonitis (SBP; 18% in PeCa vs. 8% of SOC), hyponatremia (10% vs. 0%), and infections other than SBP (4% and 16%).

A propensity score–matched analysis that included age, history of SBP, platelet count, serum albumin levels, and MELD score found no significant differences between the two groups, but there were trends in the PeCa group towards higher 90-day survival (P = .16) and a higher frequency of acute kidney injury (P = .08).

Although the appropriate patient population for the system would be small, “once you get to refractory ascites, management of these individuals is really, really challenging, especially people that had contraindications to a TIPS procedure. Anything that you can do to improve their quality of life and help with management is definitely desired,” said Nancy Reau, MD, who was asked to comment on the study. Dr. Reau is chief of the section of hepatology at Rush University Medical Center, Chicago.

The study found little difference in infection risk between the PeCa and standard of care group, but there was a trend toward more hyponatremia in the PeCa group. That could be caused by reduced contact with the health system, according to Dr. Reau, since physicians may be keeping an eye on electrolytes, diuretics, and other factors during paracentesis visits. “But as long as you’re setting up home nursing or some other way to make sure that you’re managing them appropriately, that should be something that is overcome with awareness,” said Dr. Reau.

During the question-and-answer following the presentation, Dr. Tergast was asked about the heightened frequency of hospitalizations in the PeCa group. He posited that the observation may be caused by the retrospective nature of the study. His center is a tertiary care center, which accepts referrals from all over Germany. When a problem occurs with a PeCa, patients often get referred back to the tertiary center, leading to a higher number of hospitalizations observed in that group. “So this might be a bias in the analysis,” he said.

“I think if we can optimize the treatment after discharge, we can also minimize the rehospitalization in these patients. Rehospitalization rate because of ascites was quite low,” said Dr. Tergast.

Dr. Tergast and Dr. Reau have no relevant financial disclosures.

A home-based tunneled peritoneal catheter (PeCa) drainage system provided significant relief for patients with refractory ascites who were not candidates for transjugular intrahepatic portosystemic shunt (TIPS).

For these patients, the current standard of care is repeated large volume paracentesis, but this can require frequent hospital trips that can be costly and onerous.

The PeCa system consists of one part that lays in the peritoneal cavity, then a tunnel through subcutaneous tissue and an external port where the patient can connect drainage bags. It has been tested and found to provide relief for patients with malignant ascites, but there is little data available for patients with cirrhosis, according to Tammo Lambert Tergast, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Tergast is a resident in the department of gastroenterology, hepatology, and endocrinology at Hannover (Germany) Medical School.

“Patients with refractory ascites have a very high risk for rehospitalization, AKI [acute kidney injury], and death. Our data indicate that PeCa could be a valuable new treatment option for patients with refractory ascites and contraindication for TIPS. However, the risk for hyponatremia and AKI has to be considered and further explored,” said Dr. Tergast during his presentation.

The researchers retrospectively analyzed outcomes in 152 patients with refractory ascites who received a PeCa implant and 71 patients who received standard of care (SOC), which included repeated large volume paracentesis and albumin. The median explant-free survival was 74 days, and just under 50% were explant free at 90 days.

52 patients had the PeCa system removed: 54% because of an infection, 15% because of liver transplant, 12% because of dysfunction, and 10% because of accidental removal.

Factors associated with 90-day survival included PeCa (hazard ratio, 0.52; P = .05) and each point of Model for End-Stage Liver Disease (MELD) score (HR, 1.16; P = .001). There was a trend toward a higher incidence of hyponatremia in the PeCa group (P = .09).

Hospitalizations were more common in the PeCa group (P = .035), but there was no significant difference in mortality between the two groups. Reasons for hospitalization included spontaneous bacterial peritonitis (SBP; 18% in PeCa vs. 8% of SOC), hyponatremia (10% vs. 0%), and infections other than SBP (4% and 16%).

A propensity score–matched analysis that included age, history of SBP, platelet count, serum albumin levels, and MELD score found no significant differences between the two groups, but there were trends in the PeCa group towards higher 90-day survival (P = .16) and a higher frequency of acute kidney injury (P = .08).

Although the appropriate patient population for the system would be small, “once you get to refractory ascites, management of these individuals is really, really challenging, especially people that had contraindications to a TIPS procedure. Anything that you can do to improve their quality of life and help with management is definitely desired,” said Nancy Reau, MD, who was asked to comment on the study. Dr. Reau is chief of the section of hepatology at Rush University Medical Center, Chicago.

The study found little difference in infection risk between the PeCa and standard of care group, but there was a trend toward more hyponatremia in the PeCa group. That could be caused by reduced contact with the health system, according to Dr. Reau, since physicians may be keeping an eye on electrolytes, diuretics, and other factors during paracentesis visits. “But as long as you’re setting up home nursing or some other way to make sure that you’re managing them appropriately, that should be something that is overcome with awareness,” said Dr. Reau.

During the question-and-answer following the presentation, Dr. Tergast was asked about the heightened frequency of hospitalizations in the PeCa group. He posited that the observation may be caused by the retrospective nature of the study. His center is a tertiary care center, which accepts referrals from all over Germany. When a problem occurs with a PeCa, patients often get referred back to the tertiary center, leading to a higher number of hospitalizations observed in that group. “So this might be a bias in the analysis,” he said.

“I think if we can optimize the treatment after discharge, we can also minimize the rehospitalization in these patients. Rehospitalization rate because of ascites was quite low,” said Dr. Tergast.

Dr. Tergast and Dr. Reau have no relevant financial disclosures.

A home-based tunneled peritoneal catheter (PeCa) drainage system provided significant relief for patients with refractory ascites who were not candidates for transjugular intrahepatic portosystemic shunt (TIPS).

For these patients, the current standard of care is repeated large volume paracentesis, but this can require frequent hospital trips that can be costly and onerous.

The PeCa system consists of one part that lays in the peritoneal cavity, then a tunnel through subcutaneous tissue and an external port where the patient can connect drainage bags. It has been tested and found to provide relief for patients with malignant ascites, but there is little data available for patients with cirrhosis, according to Tammo Lambert Tergast, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Tergast is a resident in the department of gastroenterology, hepatology, and endocrinology at Hannover (Germany) Medical School.

“Patients with refractory ascites have a very high risk for rehospitalization, AKI [acute kidney injury], and death. Our data indicate that PeCa could be a valuable new treatment option for patients with refractory ascites and contraindication for TIPS. However, the risk for hyponatremia and AKI has to be considered and further explored,” said Dr. Tergast during his presentation.

The researchers retrospectively analyzed outcomes in 152 patients with refractory ascites who received a PeCa implant and 71 patients who received standard of care (SOC), which included repeated large volume paracentesis and albumin. The median explant-free survival was 74 days, and just under 50% were explant free at 90 days.

52 patients had the PeCa system removed: 54% because of an infection, 15% because of liver transplant, 12% because of dysfunction, and 10% because of accidental removal.

Factors associated with 90-day survival included PeCa (hazard ratio, 0.52; P = .05) and each point of Model for End-Stage Liver Disease (MELD) score (HR, 1.16; P = .001). There was a trend toward a higher incidence of hyponatremia in the PeCa group (P = .09).

Hospitalizations were more common in the PeCa group (P = .035), but there was no significant difference in mortality between the two groups. Reasons for hospitalization included spontaneous bacterial peritonitis (SBP; 18% in PeCa vs. 8% of SOC), hyponatremia (10% vs. 0%), and infections other than SBP (4% and 16%).

A propensity score–matched analysis that included age, history of SBP, platelet count, serum albumin levels, and MELD score found no significant differences between the two groups, but there were trends in the PeCa group towards higher 90-day survival (P = .16) and a higher frequency of acute kidney injury (P = .08).

Although the appropriate patient population for the system would be small, “once you get to refractory ascites, management of these individuals is really, really challenging, especially people that had contraindications to a TIPS procedure. Anything that you can do to improve their quality of life and help with management is definitely desired,” said Nancy Reau, MD, who was asked to comment on the study. Dr. Reau is chief of the section of hepatology at Rush University Medical Center, Chicago.

The study found little difference in infection risk between the PeCa and standard of care group, but there was a trend toward more hyponatremia in the PeCa group. That could be caused by reduced contact with the health system, according to Dr. Reau, since physicians may be keeping an eye on electrolytes, diuretics, and other factors during paracentesis visits. “But as long as you’re setting up home nursing or some other way to make sure that you’re managing them appropriately, that should be something that is overcome with awareness,” said Dr. Reau.

During the question-and-answer following the presentation, Dr. Tergast was asked about the heightened frequency of hospitalizations in the PeCa group. He posited that the observation may be caused by the retrospective nature of the study. His center is a tertiary care center, which accepts referrals from all over Germany. When a problem occurs with a PeCa, patients often get referred back to the tertiary center, leading to a higher number of hospitalizations observed in that group. “So this might be a bias in the analysis,” he said.

“I think if we can optimize the treatment after discharge, we can also minimize the rehospitalization in these patients. Rehospitalization rate because of ascites was quite low,” said Dr. Tergast.

Dr. Tergast and Dr. Reau have no relevant financial disclosures.

Although the risk for liver cancer diminishes for patients with hepatitis C virus (HCV) infections for whom the virus is eliminated with direct-acting antiviral (DAA) drugs, these patients are not out of the woods, and those who do not have a sustained viral response (SVR) are at substantially higher risk of developing hepatocellular carcinoma (HCC), results of a large study show.

Among the patients with liver cirrhosis from HCV infections treated at 30 centers in Italy, a large percentage had an SVR after treatment with DAA drugs. Only a small percentage of this group subsequently developed HCC.

In contrast, not having an SVR was associated with a more than sevenfold higher risk for liver cancer, said Loreta A. Kondili, MD, PhD, from the Center for Global Health at the Istituto Superiore di Sanità, Rome, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Failure to achieve SVR after DAA treatment is strongly associated with the probability of HCC development. Older age, [HCV] genotype 3, and low platelet counts and albumin levels are independent factors of HCC development despite viral eradication,” she said.
 

Cohort study

The study findings come from the PITER Cohort Study, a prospective, multicenter observational study of a representative sample of patients with HCV.

Dr. Kondili and colleagues assessed the medium- and long-term effects of DAA therapy on HCC rates among patients with HCV-induced liver cirrhosis. Patients who had undergone a liver transplant or who had been previously diagnosed with HCC were excluded.

The investigators identified a total of 2,214 DAA-treated patients, of whom 149 (6.7%) developed de novo HCC after a median follow-up of 30 months.

From the total group, 2,064 (93%) patients had an SVR, 119 of whom (5.8%) developed HCC. Of these patients who developed HCC, 80% were diagnosed with stage B or C disease in accordance with the Barcelona Clinic Liver Cancer staging system.

For the remaining 150 patients who did not have an SVR, 30 (20%) developed de novo HCC, a difference that translated into an adjusted hazard ratio (aHR) for HCC of 7.38 (P < .01).

The time from the end of DAA therapy to a diagnosis of HCC was shorter for patients who did not have an SVR. For these patients, the 2-year HCC-free survival rate was 81%, compared with 98% for patients who had an SVR (P < .001).

As reported by Dr. Kondili, among patients who achieved an SVR, the variables significantly associated with HCC risk included older age (aHR, 1.06), platelet counts greater than the reference limit of 150,000 μL (aHR, 2.43), albumin levels >3.5 g/dL (aHR, 2.36), and diabetes (aHR, 1.53; all these variables were significant by confidence intervals).

In all, 26% of these patients died during the follow-up period, and 7.6% underwent liver transplant.

Of the patients still alive at the end of the follow-up period, 38% had active HCC.
 

Long-term follow-up required

“It’s useful to think of hepatitis C as a viral infection on one hand [and] a liver disease on the other,” commented Raymond T. Chung, MD, director of the Hepatology and Liver Center and vice chief of gastroenterology at Massachusetts General Hospital, Boston.

“In terms of thinking of elimination, we can eradicate the virus in most patients with virtually 100% success with antivirals. This has given us a false sense of comfort that it’s a ‘one and done’ process, and patients can more or less enjoy the rest of their lives free of hepatitis C,” he said.

Dr. Chung, who was not involved in the study, emphasized that despite the elimination of the virus, patients may still have significant liver fibrosis or cirrhosis. It is imperative that these patients be monitored for signs of cancer, he said.

“This is what’s important about staging patients and understanding how severe their liver disease is, because if there is advanced fibrosis, bridging fibrosis, or cirrhosis, these are patients who are going to require long-term oncology care. Their infectious disease is eliminated, but the liver disease remains,” he said.

Dr. Chung also noted that rates of liver cancer, decompensation, and liver failure are higher among patients with untreated HCV than among patients whose HCV has been eradicated or suppressed with drug treatment. In addition, patients with untreated HCV are at greater risk of requiring transplant than are patients with HCV that was treated, and there remains a residual cancer risk for patients who become HCV seronegative.

The study was funded by the Italian Ministry of Health. Dr. Kondili has financial relationships with Gilead Science and AbbVie. Dr. Chung reported no relevant financial relationships.

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

Although the risk for liver cancer diminishes for patients with hepatitis C virus (HCV) infections for whom the virus is eliminated with direct-acting antiviral (DAA) drugs, these patients are not out of the woods, and those who do not have a sustained viral response (SVR) are at substantially higher risk of developing hepatocellular carcinoma (HCC), results of a large study show.

Among the patients with liver cirrhosis from HCV infections treated at 30 centers in Italy, a large percentage had an SVR after treatment with DAA drugs. Only a small percentage of this group subsequently developed HCC.

In contrast, not having an SVR was associated with a more than sevenfold higher risk for liver cancer, said Loreta A. Kondili, MD, PhD, from the Center for Global Health at the Istituto Superiore di Sanità, Rome, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Failure to achieve SVR after DAA treatment is strongly associated with the probability of HCC development. Older age, [HCV] genotype 3, and low platelet counts and albumin levels are independent factors of HCC development despite viral eradication,” she said.
 

Cohort study

The study findings come from the PITER Cohort Study, a prospective, multicenter observational study of a representative sample of patients with HCV.

Dr. Kondili and colleagues assessed the medium- and long-term effects of DAA therapy on HCC rates among patients with HCV-induced liver cirrhosis. Patients who had undergone a liver transplant or who had been previously diagnosed with HCC were excluded.

The investigators identified a total of 2,214 DAA-treated patients, of whom 149 (6.7%) developed de novo HCC after a median follow-up of 30 months.

From the total group, 2,064 (93%) patients had an SVR, 119 of whom (5.8%) developed HCC. Of these patients who developed HCC, 80% were diagnosed with stage B or C disease in accordance with the Barcelona Clinic Liver Cancer staging system.

For the remaining 150 patients who did not have an SVR, 30 (20%) developed de novo HCC, a difference that translated into an adjusted hazard ratio (aHR) for HCC of 7.38 (P < .01).

The time from the end of DAA therapy to a diagnosis of HCC was shorter for patients who did not have an SVR. For these patients, the 2-year HCC-free survival rate was 81%, compared with 98% for patients who had an SVR (P < .001).

As reported by Dr. Kondili, among patients who achieved an SVR, the variables significantly associated with HCC risk included older age (aHR, 1.06), platelet counts greater than the reference limit of 150,000 μL (aHR, 2.43), albumin levels >3.5 g/dL (aHR, 2.36), and diabetes (aHR, 1.53; all these variables were significant by confidence intervals).

In all, 26% of these patients died during the follow-up period, and 7.6% underwent liver transplant.

Of the patients still alive at the end of the follow-up period, 38% had active HCC.
 

Long-term follow-up required

“It’s useful to think of hepatitis C as a viral infection on one hand [and] a liver disease on the other,” commented Raymond T. Chung, MD, director of the Hepatology and Liver Center and vice chief of gastroenterology at Massachusetts General Hospital, Boston.

“In terms of thinking of elimination, we can eradicate the virus in most patients with virtually 100% success with antivirals. This has given us a false sense of comfort that it’s a ‘one and done’ process, and patients can more or less enjoy the rest of their lives free of hepatitis C,” he said.

Dr. Chung, who was not involved in the study, emphasized that despite the elimination of the virus, patients may still have significant liver fibrosis or cirrhosis. It is imperative that these patients be monitored for signs of cancer, he said.

“This is what’s important about staging patients and understanding how severe their liver disease is, because if there is advanced fibrosis, bridging fibrosis, or cirrhosis, these are patients who are going to require long-term oncology care. Their infectious disease is eliminated, but the liver disease remains,” he said.

Dr. Chung also noted that rates of liver cancer, decompensation, and liver failure are higher among patients with untreated HCV than among patients whose HCV has been eradicated or suppressed with drug treatment. In addition, patients with untreated HCV are at greater risk of requiring transplant than are patients with HCV that was treated, and there remains a residual cancer risk for patients who become HCV seronegative.

The study was funded by the Italian Ministry of Health. Dr. Kondili has financial relationships with Gilead Science and AbbVie. Dr. Chung reported no relevant financial relationships.

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

Although the risk for liver cancer diminishes for patients with hepatitis C virus (HCV) infections for whom the virus is eliminated with direct-acting antiviral (DAA) drugs, these patients are not out of the woods, and those who do not have a sustained viral response (SVR) are at substantially higher risk of developing hepatocellular carcinoma (HCC), results of a large study show.

Among the patients with liver cirrhosis from HCV infections treated at 30 centers in Italy, a large percentage had an SVR after treatment with DAA drugs. Only a small percentage of this group subsequently developed HCC.

In contrast, not having an SVR was associated with a more than sevenfold higher risk for liver cancer, said Loreta A. Kondili, MD, PhD, from the Center for Global Health at the Istituto Superiore di Sanità, Rome, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Failure to achieve SVR after DAA treatment is strongly associated with the probability of HCC development. Older age, [HCV] genotype 3, and low platelet counts and albumin levels are independent factors of HCC development despite viral eradication,” she said.
 

Cohort study

The study findings come from the PITER Cohort Study, a prospective, multicenter observational study of a representative sample of patients with HCV.

Dr. Kondili and colleagues assessed the medium- and long-term effects of DAA therapy on HCC rates among patients with HCV-induced liver cirrhosis. Patients who had undergone a liver transplant or who had been previously diagnosed with HCC were excluded.

The investigators identified a total of 2,214 DAA-treated patients, of whom 149 (6.7%) developed de novo HCC after a median follow-up of 30 months.

From the total group, 2,064 (93%) patients had an SVR, 119 of whom (5.8%) developed HCC. Of these patients who developed HCC, 80% were diagnosed with stage B or C disease in accordance with the Barcelona Clinic Liver Cancer staging system.

For the remaining 150 patients who did not have an SVR, 30 (20%) developed de novo HCC, a difference that translated into an adjusted hazard ratio (aHR) for HCC of 7.38 (P < .01).

The time from the end of DAA therapy to a diagnosis of HCC was shorter for patients who did not have an SVR. For these patients, the 2-year HCC-free survival rate was 81%, compared with 98% for patients who had an SVR (P < .001).

As reported by Dr. Kondili, among patients who achieved an SVR, the variables significantly associated with HCC risk included older age (aHR, 1.06), platelet counts greater than the reference limit of 150,000 μL (aHR, 2.43), albumin levels >3.5 g/dL (aHR, 2.36), and diabetes (aHR, 1.53; all these variables were significant by confidence intervals).

In all, 26% of these patients died during the follow-up period, and 7.6% underwent liver transplant.

Of the patients still alive at the end of the follow-up period, 38% had active HCC.
 

Long-term follow-up required

“It’s useful to think of hepatitis C as a viral infection on one hand [and] a liver disease on the other,” commented Raymond T. Chung, MD, director of the Hepatology and Liver Center and vice chief of gastroenterology at Massachusetts General Hospital, Boston.

“In terms of thinking of elimination, we can eradicate the virus in most patients with virtually 100% success with antivirals. This has given us a false sense of comfort that it’s a ‘one and done’ process, and patients can more or less enjoy the rest of their lives free of hepatitis C,” he said.

Dr. Chung, who was not involved in the study, emphasized that despite the elimination of the virus, patients may still have significant liver fibrosis or cirrhosis. It is imperative that these patients be monitored for signs of cancer, he said.

“This is what’s important about staging patients and understanding how severe their liver disease is, because if there is advanced fibrosis, bridging fibrosis, or cirrhosis, these are patients who are going to require long-term oncology care. Their infectious disease is eliminated, but the liver disease remains,” he said.

Dr. Chung also noted that rates of liver cancer, decompensation, and liver failure are higher among patients with untreated HCV than among patients whose HCV has been eradicated or suppressed with drug treatment. In addition, patients with untreated HCV are at greater risk of requiring transplant than are patients with HCV that was treated, and there remains a residual cancer risk for patients who become HCV seronegative.

The study was funded by the Italian Ministry of Health. Dr. Kondili has financial relationships with Gilead Science and AbbVie. Dr. Chung reported no relevant financial relationships.

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

Fibrosis-4 index (FIB-4) scores are strongly associated with severe liver disease outcomes in a primary care population, both in patients with known chronic liver disease and those without known CLD. The result could help identify patients with CLD before their condition becomes severe.

Digital Vision/Thinkstock

FIB-4 has previously shown utility in predicting the risk of advanced fibrosis in patients with viral hepatitis B and C, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcohol-related liver disease.

“This is really important in primary care because FIB-4 is easy to calculate. Its inputs are accessible, and it is inexpensive, often taking advantage of labs that we’ve ordered anyway. And if we can use it to find advanced fibrosis, it will be critically important because we know that advanced fibrosis is associated with severe liver outcomes – these are going to be patients that we need to make sure are in touch with our hepatology colleagues,” said Andrew Schreiner, MD, during a presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Schreiner is general internist at the Medical University of South Carolina, Charleston.

He also noted that FIB-4 is playing an important role in the assessment of NAFLD and NASH. Many newer algorithms to manage NAFLD in the primary care setting rely on FIB-4, but that application is limited because NAFLD is underdiagnosed according to administrative database studies, which found rates of about 2%-5% despite the fact that estimates put it at having a prevalence of 25%-30% in the U.S. population.

To determine if FIB-4 scores could assist in identifying primary care patients at risk of severe outcomes, including cirrhosis, hepatocellular carcinoma, and liver transplant, the researchers conducted a retrospective analysis of primary care electronic health care data from 20,556 patients between 2007 and 2018 who were seen at their institution. Participants had ALT and AST values less than 500 IU/L, as well as a platelet count within two months preceding or on the day of the liver enzyme tests. They excluded individuals with known chronic or severe liver disease.

65% of patients were female, 45% were Black, and the mean BMI was 29.8 kg/m2. 64% of participants were ranked as low risk (FIB-4 ≤1.3), 29% with undetermined risk (1.3-2.67), and 7% with high risk (>2.67).

The population had more liver risk than expected. “[It is] a distribution that certainly may have more high risk and indeterminant risks than we would have anticipated, but we have seen this in external studies,” said Dr. Schreiner.

Over a mean follow-up period of 8.2 years, 11% were diagnosed with CLD: 2.3% developed NAFLD, 8.2% another CLD, and 0.5% had NAFLD and another CLD. About 4% developed a severe CLD. A severe liver outcome occurred in 2.2% of those who had been classified as FIB-4 low risk, 4.2% classified as indeterminate risk, and 20.8% of those classified as high risk.

“Troublingly,” said Dr. Schreiner, 49% of those who went on to develop a severe liver outcome had no CLD diagnosis before it occurred. “This is a tremendous opportunity to improve diagnosis in this setting.”

After adjustment for race, gender, marital status, smoking history, BMI, and various comorbidities, the researchers found a higher risk of severe liver disease associated with indeterminate FIB-4 risk score (hazard ratio, 1.62; 95% confidence interval, 1.36-1.92) and a high FIB-4 risk score (HR, 6.64; 95% CI, 5.58-7.90), compared with those with a low FIB-4 risk score. The same was true for individual liver diseases, including NAFLD (indeterminate HR, 1.88; 95% CI, 0.99-3.60; high HR, 7.32; 95% CI, 3.44-15.58), other liver diagnosis (indeterminate HR, 2.65; 95% CI, 1.93-3.63; high HR, 11.39; 95% CI, 8.53-15.20), and NAFLD plus another liver disease (intermediate HR, 2.53; 95% CI, 0.79-8.12; high HR, 6.89; 95% CI, 1.82-26.14).

Dr. Schreiner conceded that the study may not be generalizable, since FIB-4 was not designed for use in general populations, and it was conducted at a single center.

During the question-and-answer session after the talk, Dr. Schreiner was asked if the majority of the 49% who had a severe liver outcome without previous liver disease had NAFLD. He said that was the team’s hypothesis, and they are in the process of examining that data, but a significant number appear to be alcohol related. “For us in the primary care setting, it’s just another opportunity to emphasize that we have to do a better job getting exposure histories, and alcohol histories in particular, and finding ways to document those in ways that we can make diagnoses for patients and for our hepatology colleagues,” said Dr. Schreiner.

Comoderator Kathleen Corey, MD, asked Dr. Schreiner if he had any concerns about false positives from FIB-4 screening, and whether that could lead to overtreatment. “We’ve seen other screening tests leading to patient distress and overutilization of resources. How do you think we might be able to mitigate that?” asked Dr. Corey, who is an assistant professor of medicine at Harvard Medical School and director of the Fatty Liver Clinic at Massachusetts General Hospital, both in Boston.

Dr. Schreiner underscored the need for more physician education about FIB-4, both its potential and its pitfalls, since many primary care providers don’t use it or even know about it. “FIB-4 is very popular in the hepatology literature, but in primary care, we don’t talk about it as often. So I think educational efforts about its possible utility, about some of the drawbacks, or some of the things that might lead to inappropriately positive results – like advanced age, for those of us who see patients 60 and older. Those are really important considerations both for the patient and the provider for management of expectations and concerns. I’m worried too about application in our younger cohorts. The explosion of NAFLD in adolescence, and the likelihood that we might get a false negative in maybe a 28-year-old who might have problematic disease, is a concern as well,” said Dr. Schreiner.

Dr. Schreiner has no relevant financial disclosures. Dr. Corey has been on an advisory committee or review panel for Bristol-Myers Squibb, Novo Nordisk, and Gilead. She has consulted for Novo Nordisk and received research support from BMS, Boehringer Ingelheim, Novartis, and Boehringer Ingelheim.

Fibrosis-4 index (FIB-4) scores are strongly associated with severe liver disease outcomes in a primary care population, both in patients with known chronic liver disease and those without known CLD. The result could help identify patients with CLD before their condition becomes severe.

Digital Vision/Thinkstock

FIB-4 has previously shown utility in predicting the risk of advanced fibrosis in patients with viral hepatitis B and C, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcohol-related liver disease.

“This is really important in primary care because FIB-4 is easy to calculate. Its inputs are accessible, and it is inexpensive, often taking advantage of labs that we’ve ordered anyway. And if we can use it to find advanced fibrosis, it will be critically important because we know that advanced fibrosis is associated with severe liver outcomes – these are going to be patients that we need to make sure are in touch with our hepatology colleagues,” said Andrew Schreiner, MD, during a presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Schreiner is general internist at the Medical University of South Carolina, Charleston.

He also noted that FIB-4 is playing an important role in the assessment of NAFLD and NASH. Many newer algorithms to manage NAFLD in the primary care setting rely on FIB-4, but that application is limited because NAFLD is underdiagnosed according to administrative database studies, which found rates of about 2%-5% despite the fact that estimates put it at having a prevalence of 25%-30% in the U.S. population.

To determine if FIB-4 scores could assist in identifying primary care patients at risk of severe outcomes, including cirrhosis, hepatocellular carcinoma, and liver transplant, the researchers conducted a retrospective analysis of primary care electronic health care data from 20,556 patients between 2007 and 2018 who were seen at their institution. Participants had ALT and AST values less than 500 IU/L, as well as a platelet count within two months preceding or on the day of the liver enzyme tests. They excluded individuals with known chronic or severe liver disease.

65% of patients were female, 45% were Black, and the mean BMI was 29.8 kg/m2. 64% of participants were ranked as low risk (FIB-4 ≤1.3), 29% with undetermined risk (1.3-2.67), and 7% with high risk (>2.67).

The population had more liver risk than expected. “[It is] a distribution that certainly may have more high risk and indeterminant risks than we would have anticipated, but we have seen this in external studies,” said Dr. Schreiner.

Over a mean follow-up period of 8.2 years, 11% were diagnosed with CLD: 2.3% developed NAFLD, 8.2% another CLD, and 0.5% had NAFLD and another CLD. About 4% developed a severe CLD. A severe liver outcome occurred in 2.2% of those who had been classified as FIB-4 low risk, 4.2% classified as indeterminate risk, and 20.8% of those classified as high risk.

“Troublingly,” said Dr. Schreiner, 49% of those who went on to develop a severe liver outcome had no CLD diagnosis before it occurred. “This is a tremendous opportunity to improve diagnosis in this setting.”

After adjustment for race, gender, marital status, smoking history, BMI, and various comorbidities, the researchers found a higher risk of severe liver disease associated with indeterminate FIB-4 risk score (hazard ratio, 1.62; 95% confidence interval, 1.36-1.92) and a high FIB-4 risk score (HR, 6.64; 95% CI, 5.58-7.90), compared with those with a low FIB-4 risk score. The same was true for individual liver diseases, including NAFLD (indeterminate HR, 1.88; 95% CI, 0.99-3.60; high HR, 7.32; 95% CI, 3.44-15.58), other liver diagnosis (indeterminate HR, 2.65; 95% CI, 1.93-3.63; high HR, 11.39; 95% CI, 8.53-15.20), and NAFLD plus another liver disease (intermediate HR, 2.53; 95% CI, 0.79-8.12; high HR, 6.89; 95% CI, 1.82-26.14).

Dr. Schreiner conceded that the study may not be generalizable, since FIB-4 was not designed for use in general populations, and it was conducted at a single center.

During the question-and-answer session after the talk, Dr. Schreiner was asked if the majority of the 49% who had a severe liver outcome without previous liver disease had NAFLD. He said that was the team’s hypothesis, and they are in the process of examining that data, but a significant number appear to be alcohol related. “For us in the primary care setting, it’s just another opportunity to emphasize that we have to do a better job getting exposure histories, and alcohol histories in particular, and finding ways to document those in ways that we can make diagnoses for patients and for our hepatology colleagues,” said Dr. Schreiner.

Comoderator Kathleen Corey, MD, asked Dr. Schreiner if he had any concerns about false positives from FIB-4 screening, and whether that could lead to overtreatment. “We’ve seen other screening tests leading to patient distress and overutilization of resources. How do you think we might be able to mitigate that?” asked Dr. Corey, who is an assistant professor of medicine at Harvard Medical School and director of the Fatty Liver Clinic at Massachusetts General Hospital, both in Boston.

Dr. Schreiner underscored the need for more physician education about FIB-4, both its potential and its pitfalls, since many primary care providers don’t use it or even know about it. “FIB-4 is very popular in the hepatology literature, but in primary care, we don’t talk about it as often. So I think educational efforts about its possible utility, about some of the drawbacks, or some of the things that might lead to inappropriately positive results – like advanced age, for those of us who see patients 60 and older. Those are really important considerations both for the patient and the provider for management of expectations and concerns. I’m worried too about application in our younger cohorts. The explosion of NAFLD in adolescence, and the likelihood that we might get a false negative in maybe a 28-year-old who might have problematic disease, is a concern as well,” said Dr. Schreiner.

Dr. Schreiner has no relevant financial disclosures. Dr. Corey has been on an advisory committee or review panel for Bristol-Myers Squibb, Novo Nordisk, and Gilead. She has consulted for Novo Nordisk and received research support from BMS, Boehringer Ingelheim, Novartis, and Boehringer Ingelheim.

Fibrosis-4 index (FIB-4) scores are strongly associated with severe liver disease outcomes in a primary care population, both in patients with known chronic liver disease and those without known CLD. The result could help identify patients with CLD before their condition becomes severe.

Digital Vision/Thinkstock

FIB-4 has previously shown utility in predicting the risk of advanced fibrosis in patients with viral hepatitis B and C, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcohol-related liver disease.

“This is really important in primary care because FIB-4 is easy to calculate. Its inputs are accessible, and it is inexpensive, often taking advantage of labs that we’ve ordered anyway. And if we can use it to find advanced fibrosis, it will be critically important because we know that advanced fibrosis is associated with severe liver outcomes – these are going to be patients that we need to make sure are in touch with our hepatology colleagues,” said Andrew Schreiner, MD, during a presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Schreiner is general internist at the Medical University of South Carolina, Charleston.

He also noted that FIB-4 is playing an important role in the assessment of NAFLD and NASH. Many newer algorithms to manage NAFLD in the primary care setting rely on FIB-4, but that application is limited because NAFLD is underdiagnosed according to administrative database studies, which found rates of about 2%-5% despite the fact that estimates put it at having a prevalence of 25%-30% in the U.S. population.

To determine if FIB-4 scores could assist in identifying primary care patients at risk of severe outcomes, including cirrhosis, hepatocellular carcinoma, and liver transplant, the researchers conducted a retrospective analysis of primary care electronic health care data from 20,556 patients between 2007 and 2018 who were seen at their institution. Participants had ALT and AST values less than 500 IU/L, as well as a platelet count within two months preceding or on the day of the liver enzyme tests. They excluded individuals with known chronic or severe liver disease.

65% of patients were female, 45% were Black, and the mean BMI was 29.8 kg/m2. 64% of participants were ranked as low risk (FIB-4 ≤1.3), 29% with undetermined risk (1.3-2.67), and 7% with high risk (>2.67).

The population had more liver risk than expected. “[It is] a distribution that certainly may have more high risk and indeterminant risks than we would have anticipated, but we have seen this in external studies,” said Dr. Schreiner.

Over a mean follow-up period of 8.2 years, 11% were diagnosed with CLD: 2.3% developed NAFLD, 8.2% another CLD, and 0.5% had NAFLD and another CLD. About 4% developed a severe CLD. A severe liver outcome occurred in 2.2% of those who had been classified as FIB-4 low risk, 4.2% classified as indeterminate risk, and 20.8% of those classified as high risk.

“Troublingly,” said Dr. Schreiner, 49% of those who went on to develop a severe liver outcome had no CLD diagnosis before it occurred. “This is a tremendous opportunity to improve diagnosis in this setting.”

After adjustment for race, gender, marital status, smoking history, BMI, and various comorbidities, the researchers found a higher risk of severe liver disease associated with indeterminate FIB-4 risk score (hazard ratio, 1.62; 95% confidence interval, 1.36-1.92) and a high FIB-4 risk score (HR, 6.64; 95% CI, 5.58-7.90), compared with those with a low FIB-4 risk score. The same was true for individual liver diseases, including NAFLD (indeterminate HR, 1.88; 95% CI, 0.99-3.60; high HR, 7.32; 95% CI, 3.44-15.58), other liver diagnosis (indeterminate HR, 2.65; 95% CI, 1.93-3.63; high HR, 11.39; 95% CI, 8.53-15.20), and NAFLD plus another liver disease (intermediate HR, 2.53; 95% CI, 0.79-8.12; high HR, 6.89; 95% CI, 1.82-26.14).

Dr. Schreiner conceded that the study may not be generalizable, since FIB-4 was not designed for use in general populations, and it was conducted at a single center.

During the question-and-answer session after the talk, Dr. Schreiner was asked if the majority of the 49% who had a severe liver outcome without previous liver disease had NAFLD. He said that was the team’s hypothesis, and they are in the process of examining that data, but a significant number appear to be alcohol related. “For us in the primary care setting, it’s just another opportunity to emphasize that we have to do a better job getting exposure histories, and alcohol histories in particular, and finding ways to document those in ways that we can make diagnoses for patients and for our hepatology colleagues,” said Dr. Schreiner.

Comoderator Kathleen Corey, MD, asked Dr. Schreiner if he had any concerns about false positives from FIB-4 screening, and whether that could lead to overtreatment. “We’ve seen other screening tests leading to patient distress and overutilization of resources. How do you think we might be able to mitigate that?” asked Dr. Corey, who is an assistant professor of medicine at Harvard Medical School and director of the Fatty Liver Clinic at Massachusetts General Hospital, both in Boston.

Dr. Schreiner underscored the need for more physician education about FIB-4, both its potential and its pitfalls, since many primary care providers don’t use it or even know about it. “FIB-4 is very popular in the hepatology literature, but in primary care, we don’t talk about it as often. So I think educational efforts about its possible utility, about some of the drawbacks, or some of the things that might lead to inappropriately positive results – like advanced age, for those of us who see patients 60 and older. Those are really important considerations both for the patient and the provider for management of expectations and concerns. I’m worried too about application in our younger cohorts. The explosion of NAFLD in adolescence, and the likelihood that we might get a false negative in maybe a 28-year-old who might have problematic disease, is a concern as well,” said Dr. Schreiner.

Dr. Schreiner has no relevant financial disclosures. Dr. Corey has been on an advisory committee or review panel for Bristol-Myers Squibb, Novo Nordisk, and Gilead. She has consulted for Novo Nordisk and received research support from BMS, Boehringer Ingelheim, Novartis, and Boehringer Ingelheim.

A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

A “virtual” liver transplant center servicing Vermont and New Hampshire has improved access to liver transplant listing among patients in rural areas of the region, according to a new analysis.

The virtual center was established in 2016 at Dartmouth Hitchcock Medical Center, and it allows patients to receive pre–liver transplant evaluations, testing, and care and posttransplant follow-up there rather than at the liver transplant center that conducts the surgery. The center includes two hepatologists, two associate care providers, and a nurse liver transplant coordinator at DHMC, and led to increased transplant listing in the vicinity, according to Margaret Liu, MD, who presented the study at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“The initiation of this Virtual Liver Transplant Center has been able to provide patients with the ability to get a full liver transplant workup and evaluation at a center near their home rather than the often time-consuming and costly process of potentially multiple trips to a liver transplant center up to 250 miles away for a full transplant evaluation,” said Dr. Liu in an interview. Dr. Liu is an internal medicine resident at Dartmouth Hitchcock Medical Center.

“Our results did show that the initiation of a virtual liver transplant center correlated with an increased and sustained liver transplant listing rate within 60 miles of Dartmouth over that particular study period. Conversely there was no significant change in the listing rate of New Hampshire zip codes that were within 60 miles of the nearest transplant center during the same study period,” said Dr. Liu.

The center receives referrals of patients who are potential candidates for liver transplant listing from practices throughout New Hampshire and Vermont, or from their own center. Their specialists conduct full testing, including a full liver transplant workup that includes evaluation of the patient’s general health and social factors, prior to sending the patient to the actual liver transplant center for their evaluation and transplant surgery. “We essentially do all of the pre–liver transplant workup, a formal liver transplant evaluation, and then the whole packet gets sent to an actual liver transplant center to expedite the process of getting listed for liver transplant. We’re able to streamline the process, so they get everything done here at a hospital near their home. If that requires multiple trips, it’s a lot more doable for the patients,” said Dr. Liu.

The researchers defined urban areas as having more than 50,000 people per square mile and within 30 miles of the nearest hospital, and rural as fewer than 10,000 and more than 60 miles from the nearest hospital. They used the Scientific Registry of Transplant Recipients to determine the number of liver transplant listings per zip code.

Between 2015 and 2019, the frequency of liver transplant listings per 10,000 people remained nearly unchanged in the metropolitan area of southern New Hampshire, ranging from around 0.36 to 0.75. In the rural area within 60 miles of DHMC, the frequency increased from about 0.7 per 10,000 in 2015 to about 1.4 in 2016 and 0.9 in 2017. There was an increase to nearly 3 in 10,000 in 2018, and the frequency was just over 2 in 2019.

The model has the potential to be used in other areas, according to Dr. Liu. “This could potentially be implemented in other rural areas that do not have a transplant center or don’t have a formal liver transplant evaluation process,” said Dr. Liu.

While other centers may have taken on some aspects of liver transplant evaluation and posttransplant care, the Virtual Liver Transplant Center is unique in that a great deal of effort has gone into covering all of a patient’s needs for the liver transplant evaluation. “It’s really the formalization that, from what I have researched, has not been done before,” said Dr. Liu.

The model addresses transplant-listing disparity, as well as improves patient quality of life through reduction in travel, according to Mayur Brahmania, MD, of Western University, London, Ont., who moderated the session. “They’ve proven that they can get more of their patients listed over the study period, which I think is amazing. The next step, I think, would be about whether getting them onto the transplant list actually made a difference in terms of outcome – looking at their wait list mortality, looking at how many of these patients actually got a liver transplantation. That’s the ultimate outcome,” said Dr. Brahmania.

He also noted the challenge of setting up a virtual center. “You have to have allied health staff – addiction counselors, physical therapists, dietitians, social workers. You need to have the appropriate ancillary services like cardiac testing, pulmonary function testing. It’s quite an endeavor, and if the program isn’t too enthusiastic or doesn’t have a local champion, it’s really hard to get something like this started off. So kudos to them for taking on this challenge and getting this up and running over the last 5 years,” said Dr. Brahmania.

Dr. Liu and Dr. Brahmania have no relevant financial disclosures.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

A “virtual” liver transplant center servicing Vermont and New Hampshire has improved access to liver transplant listing among patients in rural areas of the region, according to a new analysis.

The virtual center was established in 2016 at Dartmouth Hitchcock Medical Center, and it allows patients to receive pre–liver transplant evaluations, testing, and care and posttransplant follow-up there rather than at the liver transplant center that conducts the surgery. The center includes two hepatologists, two associate care providers, and a nurse liver transplant coordinator at DHMC, and led to increased transplant listing in the vicinity, according to Margaret Liu, MD, who presented the study at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“The initiation of this Virtual Liver Transplant Center has been able to provide patients with the ability to get a full liver transplant workup and evaluation at a center near their home rather than the often time-consuming and costly process of potentially multiple trips to a liver transplant center up to 250 miles away for a full transplant evaluation,” said Dr. Liu in an interview. Dr. Liu is an internal medicine resident at Dartmouth Hitchcock Medical Center.

“Our results did show that the initiation of a virtual liver transplant center correlated with an increased and sustained liver transplant listing rate within 60 miles of Dartmouth over that particular study period. Conversely there was no significant change in the listing rate of New Hampshire zip codes that were within 60 miles of the nearest transplant center during the same study period,” said Dr. Liu.

The center receives referrals of patients who are potential candidates for liver transplant listing from practices throughout New Hampshire and Vermont, or from their own center. Their specialists conduct full testing, including a full liver transplant workup that includes evaluation of the patient’s general health and social factors, prior to sending the patient to the actual liver transplant center for their evaluation and transplant surgery. “We essentially do all of the pre–liver transplant workup, a formal liver transplant evaluation, and then the whole packet gets sent to an actual liver transplant center to expedite the process of getting listed for liver transplant. We’re able to streamline the process, so they get everything done here at a hospital near their home. If that requires multiple trips, it’s a lot more doable for the patients,” said Dr. Liu.

The researchers defined urban areas as having more than 50,000 people per square mile and within 30 miles of the nearest hospital, and rural as fewer than 10,000 and more than 60 miles from the nearest hospital. They used the Scientific Registry of Transplant Recipients to determine the number of liver transplant listings per zip code.

Between 2015 and 2019, the frequency of liver transplant listings per 10,000 people remained nearly unchanged in the metropolitan area of southern New Hampshire, ranging from around 0.36 to 0.75. In the rural area within 60 miles of DHMC, the frequency increased from about 0.7 per 10,000 in 2015 to about 1.4 in 2016 and 0.9 in 2017. There was an increase to nearly 3 in 10,000 in 2018, and the frequency was just over 2 in 2019.

The model has the potential to be used in other areas, according to Dr. Liu. “This could potentially be implemented in other rural areas that do not have a transplant center or don’t have a formal liver transplant evaluation process,” said Dr. Liu.

While other centers may have taken on some aspects of liver transplant evaluation and posttransplant care, the Virtual Liver Transplant Center is unique in that a great deal of effort has gone into covering all of a patient’s needs for the liver transplant evaluation. “It’s really the formalization that, from what I have researched, has not been done before,” said Dr. Liu.

The model addresses transplant-listing disparity, as well as improves patient quality of life through reduction in travel, according to Mayur Brahmania, MD, of Western University, London, Ont., who moderated the session. “They’ve proven that they can get more of their patients listed over the study period, which I think is amazing. The next step, I think, would be about whether getting them onto the transplant list actually made a difference in terms of outcome – looking at their wait list mortality, looking at how many of these patients actually got a liver transplantation. That’s the ultimate outcome,” said Dr. Brahmania.

He also noted the challenge of setting up a virtual center. “You have to have allied health staff – addiction counselors, physical therapists, dietitians, social workers. You need to have the appropriate ancillary services like cardiac testing, pulmonary function testing. It’s quite an endeavor, and if the program isn’t too enthusiastic or doesn’t have a local champion, it’s really hard to get something like this started off. So kudos to them for taking on this challenge and getting this up and running over the last 5 years,” said Dr. Brahmania.

Dr. Liu and Dr. Brahmania have no relevant financial disclosures.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

A “virtual” liver transplant center servicing Vermont and New Hampshire has improved access to liver transplant listing among patients in rural areas of the region, according to a new analysis.

The virtual center was established in 2016 at Dartmouth Hitchcock Medical Center, and it allows patients to receive pre–liver transplant evaluations, testing, and care and posttransplant follow-up there rather than at the liver transplant center that conducts the surgery. The center includes two hepatologists, two associate care providers, and a nurse liver transplant coordinator at DHMC, and led to increased transplant listing in the vicinity, according to Margaret Liu, MD, who presented the study at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“The initiation of this Virtual Liver Transplant Center has been able to provide patients with the ability to get a full liver transplant workup and evaluation at a center near their home rather than the often time-consuming and costly process of potentially multiple trips to a liver transplant center up to 250 miles away for a full transplant evaluation,” said Dr. Liu in an interview. Dr. Liu is an internal medicine resident at Dartmouth Hitchcock Medical Center.

“Our results did show that the initiation of a virtual liver transplant center correlated with an increased and sustained liver transplant listing rate within 60 miles of Dartmouth over that particular study period. Conversely there was no significant change in the listing rate of New Hampshire zip codes that were within 60 miles of the nearest transplant center during the same study period,” said Dr. Liu.

The center receives referrals of patients who are potential candidates for liver transplant listing from practices throughout New Hampshire and Vermont, or from their own center. Their specialists conduct full testing, including a full liver transplant workup that includes evaluation of the patient’s general health and social factors, prior to sending the patient to the actual liver transplant center for their evaluation and transplant surgery. “We essentially do all of the pre–liver transplant workup, a formal liver transplant evaluation, and then the whole packet gets sent to an actual liver transplant center to expedite the process of getting listed for liver transplant. We’re able to streamline the process, so they get everything done here at a hospital near their home. If that requires multiple trips, it’s a lot more doable for the patients,” said Dr. Liu.

The researchers defined urban areas as having more than 50,000 people per square mile and within 30 miles of the nearest hospital, and rural as fewer than 10,000 and more than 60 miles from the nearest hospital. They used the Scientific Registry of Transplant Recipients to determine the number of liver transplant listings per zip code.

Between 2015 and 2019, the frequency of liver transplant listings per 10,000 people remained nearly unchanged in the metropolitan area of southern New Hampshire, ranging from around 0.36 to 0.75. In the rural area within 60 miles of DHMC, the frequency increased from about 0.7 per 10,000 in 2015 to about 1.4 in 2016 and 0.9 in 2017. There was an increase to nearly 3 in 10,000 in 2018, and the frequency was just over 2 in 2019.

The model has the potential to be used in other areas, according to Dr. Liu. “This could potentially be implemented in other rural areas that do not have a transplant center or don’t have a formal liver transplant evaluation process,” said Dr. Liu.

While other centers may have taken on some aspects of liver transplant evaluation and posttransplant care, the Virtual Liver Transplant Center is unique in that a great deal of effort has gone into covering all of a patient’s needs for the liver transplant evaluation. “It’s really the formalization that, from what I have researched, has not been done before,” said Dr. Liu.

The model addresses transplant-listing disparity, as well as improves patient quality of life through reduction in travel, according to Mayur Brahmania, MD, of Western University, London, Ont., who moderated the session. “They’ve proven that they can get more of their patients listed over the study period, which I think is amazing. The next step, I think, would be about whether getting them onto the transplant list actually made a difference in terms of outcome – looking at their wait list mortality, looking at how many of these patients actually got a liver transplantation. That’s the ultimate outcome,” said Dr. Brahmania.

He also noted the challenge of setting up a virtual center. “You have to have allied health staff – addiction counselors, physical therapists, dietitians, social workers. You need to have the appropriate ancillary services like cardiac testing, pulmonary function testing. It’s quite an endeavor, and if the program isn’t too enthusiastic or doesn’t have a local champion, it’s really hard to get something like this started off. So kudos to them for taking on this challenge and getting this up and running over the last 5 years,” said Dr. Brahmania.

Dr. Liu and Dr. Brahmania have no relevant financial disclosures.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

Two-fifths of adolescents and young adults in the United States may have nonalcoholic fatty liver disease (NAFLD), many with significant or advanced fibrosis, results of a nationwide surveillance study suggest.

In addition, among those who drink alcohol in excess, slightly more than half may have alcohol-associated fatty liver disease (ALD) that may lead to moderate to severe fibrosis in a substantial proportion, said Naim Alkhouri, MD, from Arizona Liver Health, Peoria, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Efforts should focus on increasing awareness of the burden of ALD and NAFLD in this population and [mitigating] modifiable risk factors to prevent disease development and disease progression to potentially advanced fibrosis and cirrhosis,” he said.
 

Liver stiffness measured

Unlike previous studies that relied on liver enzyme levels or ultrasonography to estimate the prevalence of fatty liver disease among adolescents and young adults in the United States, Dr. Alkhouri and colleagues used valid liver ultrasonographic elastography (FibroScan) measurements, recorded during 2017-2018, from the National Health and Nutrition Examination Survey (NHANES) database.

The sample included participants aged 15 to 39 years. Those with viral hepatitis, alanine aminotransferase (ALT) levels greater than 500 U/L, or pregnancy were excluded.

The investigators divided the participants into those with excessive alcohol consumption, defined using the NHANES Alcohol Use Questionnaire as having more than two drinks per day for males or more than one drink per day for females, and those with no excessive alcohol consumption.

The authors used controlled attenuation parameters to identify participants with suspected ALD or NAFLD.

They then used liver stiffness measurement cutoffs of greater than or equal to 7.5 kPa to identify moderate fibrosis and greater than or equal to 9.5 kPa to identify severe fibrosis in those with evidence of ALD and cutoffs of greater than or equal to 6.1 kPa and greater than or equal to 7.1 kPa, respectively, in those with suspected NAFLD.

The cutoffs were chosen to maximize sensitivity, as determined from published literature, Dr. Alkhouri said.
 

Uncovering a high prevalence of ALD and NAFLD

The final sample comprised 1,319 participants, including 100 with excessive alcohol use and 1,219 without.

The heavy drinkers were significantly more likely to be older, male, White, current smokers, have lower platelet counts, higher aspartate aminotransferase (AST) and ALT levels, and higher mean corpuscular volumes.

Among the excessive drinkers, 52% had ALD. Of this group, 87.7% had either no or mild fibrosis, and 12.3% had moderate to severe fibrosis.

Among patients with excessive alcohol consumption, significant predictors of ALD included male sex, higher body mass index, ALT greater than the upper limit of normal, and higher A1c percentage.

Among those who were moderate drinkers or abstemious, 40% had NAFLD. Of this subgroup, 68.9% had no or mild fibrosis, and 31.1% had moderate to severe fibrosis.

Predictors of NAFLD in this group included older age, male sex, higher body mass index, and elevated ALT, AST, albumin, platelet counts, and A1c.
 

Is drinking underreported?

In a question-and-answer session following the presentation, co-moderator Miriam B. Vos, MD, a pediatric hepatologist at Children’s Healthcare of Atlanta, asked Dr. Alkhouri about his confidence in the accuracy of the measurements of alcohol consumption and whether there could be significant overlap between the ALD and NAFLD populations.

Dr. Alkhouri noted that he and his colleagues relied on items 121 and 130 of the NHANES Alcohol Use Questionnaire, which are self-reported by participants.

“Obviously, we’re not going to get honest answers all the time,” he said. “We’ve seen even in NASH [nonalcoholic steatohepatitis] clinical trials that when patients say they do not drink any alcohol, if you actually look for alcohol metabolites, up to 20% may have some evidence of alcohol consumption.

“I’m sure there’s a lot of overlap, but there’s no formal assessment,” he added.

Dr. Alkhouri noted that among the cohort with ALD, obesity and increased A1c were prevalent, “so it goes both ways. I think NAFLD can also contribute to progression of ALD, and that’s why we need to study another entity called ‘both alcoholic and nonalcoholic fatty liver disease.’”

Dr. Vos suggested that biomarkers may be useful for detecting alcohol use among patients with NAFLD and for further study of the progression of NAFLD to ALD.

No source of funding for the study has been disclosed. Dr. Alkhouri and Dr. Vos reported no relevant financial relationships.

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

Two-fifths of adolescents and young adults in the United States may have nonalcoholic fatty liver disease (NAFLD), many with significant or advanced fibrosis, results of a nationwide surveillance study suggest.

In addition, among those who drink alcohol in excess, slightly more than half may have alcohol-associated fatty liver disease (ALD) that may lead to moderate to severe fibrosis in a substantial proportion, said Naim Alkhouri, MD, from Arizona Liver Health, Peoria, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Efforts should focus on increasing awareness of the burden of ALD and NAFLD in this population and [mitigating] modifiable risk factors to prevent disease development and disease progression to potentially advanced fibrosis and cirrhosis,” he said.
 

Liver stiffness measured

Unlike previous studies that relied on liver enzyme levels or ultrasonography to estimate the prevalence of fatty liver disease among adolescents and young adults in the United States, Dr. Alkhouri and colleagues used valid liver ultrasonographic elastography (FibroScan) measurements, recorded during 2017-2018, from the National Health and Nutrition Examination Survey (NHANES) database.

The sample included participants aged 15 to 39 years. Those with viral hepatitis, alanine aminotransferase (ALT) levels greater than 500 U/L, or pregnancy were excluded.

The investigators divided the participants into those with excessive alcohol consumption, defined using the NHANES Alcohol Use Questionnaire as having more than two drinks per day for males or more than one drink per day for females, and those with no excessive alcohol consumption.

The authors used controlled attenuation parameters to identify participants with suspected ALD or NAFLD.

They then used liver stiffness measurement cutoffs of greater than or equal to 7.5 kPa to identify moderate fibrosis and greater than or equal to 9.5 kPa to identify severe fibrosis in those with evidence of ALD and cutoffs of greater than or equal to 6.1 kPa and greater than or equal to 7.1 kPa, respectively, in those with suspected NAFLD.

The cutoffs were chosen to maximize sensitivity, as determined from published literature, Dr. Alkhouri said.
 

Uncovering a high prevalence of ALD and NAFLD

The final sample comprised 1,319 participants, including 100 with excessive alcohol use and 1,219 without.

The heavy drinkers were significantly more likely to be older, male, White, current smokers, have lower platelet counts, higher aspartate aminotransferase (AST) and ALT levels, and higher mean corpuscular volumes.

Among the excessive drinkers, 52% had ALD. Of this group, 87.7% had either no or mild fibrosis, and 12.3% had moderate to severe fibrosis.

Among patients with excessive alcohol consumption, significant predictors of ALD included male sex, higher body mass index, ALT greater than the upper limit of normal, and higher A1c percentage.

Among those who were moderate drinkers or abstemious, 40% had NAFLD. Of this subgroup, 68.9% had no or mild fibrosis, and 31.1% had moderate to severe fibrosis.

Predictors of NAFLD in this group included older age, male sex, higher body mass index, and elevated ALT, AST, albumin, platelet counts, and A1c.
 

Is drinking underreported?

In a question-and-answer session following the presentation, co-moderator Miriam B. Vos, MD, a pediatric hepatologist at Children’s Healthcare of Atlanta, asked Dr. Alkhouri about his confidence in the accuracy of the measurements of alcohol consumption and whether there could be significant overlap between the ALD and NAFLD populations.

Dr. Alkhouri noted that he and his colleagues relied on items 121 and 130 of the NHANES Alcohol Use Questionnaire, which are self-reported by participants.

“Obviously, we’re not going to get honest answers all the time,” he said. “We’ve seen even in NASH [nonalcoholic steatohepatitis] clinical trials that when patients say they do not drink any alcohol, if you actually look for alcohol metabolites, up to 20% may have some evidence of alcohol consumption.

“I’m sure there’s a lot of overlap, but there’s no formal assessment,” he added.

Dr. Alkhouri noted that among the cohort with ALD, obesity and increased A1c were prevalent, “so it goes both ways. I think NAFLD can also contribute to progression of ALD, and that’s why we need to study another entity called ‘both alcoholic and nonalcoholic fatty liver disease.’”

Dr. Vos suggested that biomarkers may be useful for detecting alcohol use among patients with NAFLD and for further study of the progression of NAFLD to ALD.

No source of funding for the study has been disclosed. Dr. Alkhouri and Dr. Vos reported no relevant financial relationships.

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

Two-fifths of adolescents and young adults in the United States may have nonalcoholic fatty liver disease (NAFLD), many with significant or advanced fibrosis, results of a nationwide surveillance study suggest.

In addition, among those who drink alcohol in excess, slightly more than half may have alcohol-associated fatty liver disease (ALD) that may lead to moderate to severe fibrosis in a substantial proportion, said Naim Alkhouri, MD, from Arizona Liver Health, Peoria, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Efforts should focus on increasing awareness of the burden of ALD and NAFLD in this population and [mitigating] modifiable risk factors to prevent disease development and disease progression to potentially advanced fibrosis and cirrhosis,” he said.
 

Liver stiffness measured

Unlike previous studies that relied on liver enzyme levels or ultrasonography to estimate the prevalence of fatty liver disease among adolescents and young adults in the United States, Dr. Alkhouri and colleagues used valid liver ultrasonographic elastography (FibroScan) measurements, recorded during 2017-2018, from the National Health and Nutrition Examination Survey (NHANES) database.

The sample included participants aged 15 to 39 years. Those with viral hepatitis, alanine aminotransferase (ALT) levels greater than 500 U/L, or pregnancy were excluded.

The investigators divided the participants into those with excessive alcohol consumption, defined using the NHANES Alcohol Use Questionnaire as having more than two drinks per day for males or more than one drink per day for females, and those with no excessive alcohol consumption.

The authors used controlled attenuation parameters to identify participants with suspected ALD or NAFLD.

They then used liver stiffness measurement cutoffs of greater than or equal to 7.5 kPa to identify moderate fibrosis and greater than or equal to 9.5 kPa to identify severe fibrosis in those with evidence of ALD and cutoffs of greater than or equal to 6.1 kPa and greater than or equal to 7.1 kPa, respectively, in those with suspected NAFLD.

The cutoffs were chosen to maximize sensitivity, as determined from published literature, Dr. Alkhouri said.
 

Uncovering a high prevalence of ALD and NAFLD

The final sample comprised 1,319 participants, including 100 with excessive alcohol use and 1,219 without.

The heavy drinkers were significantly more likely to be older, male, White, current smokers, have lower platelet counts, higher aspartate aminotransferase (AST) and ALT levels, and higher mean corpuscular volumes.

Among the excessive drinkers, 52% had ALD. Of this group, 87.7% had either no or mild fibrosis, and 12.3% had moderate to severe fibrosis.

Among patients with excessive alcohol consumption, significant predictors of ALD included male sex, higher body mass index, ALT greater than the upper limit of normal, and higher A1c percentage.

Among those who were moderate drinkers or abstemious, 40% had NAFLD. Of this subgroup, 68.9% had no or mild fibrosis, and 31.1% had moderate to severe fibrosis.

Predictors of NAFLD in this group included older age, male sex, higher body mass index, and elevated ALT, AST, albumin, platelet counts, and A1c.
 

Is drinking underreported?

In a question-and-answer session following the presentation, co-moderator Miriam B. Vos, MD, a pediatric hepatologist at Children’s Healthcare of Atlanta, asked Dr. Alkhouri about his confidence in the accuracy of the measurements of alcohol consumption and whether there could be significant overlap between the ALD and NAFLD populations.

Dr. Alkhouri noted that he and his colleagues relied on items 121 and 130 of the NHANES Alcohol Use Questionnaire, which are self-reported by participants.

“Obviously, we’re not going to get honest answers all the time,” he said. “We’ve seen even in NASH [nonalcoholic steatohepatitis] clinical trials that when patients say they do not drink any alcohol, if you actually look for alcohol metabolites, up to 20% may have some evidence of alcohol consumption.

“I’m sure there’s a lot of overlap, but there’s no formal assessment,” he added.

Dr. Alkhouri noted that among the cohort with ALD, obesity and increased A1c were prevalent, “so it goes both ways. I think NAFLD can also contribute to progression of ALD, and that’s why we need to study another entity called ‘both alcoholic and nonalcoholic fatty liver disease.’”

Dr. Vos suggested that biomarkers may be useful for detecting alcohol use among patients with NAFLD and for further study of the progression of NAFLD to ALD.

No source of funding for the study has been disclosed. Dr. Alkhouri and Dr. Vos reported no relevant financial relationships.

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

More than half of chronic hepatitis B e antigen–negative patients who withdraw from nucleoside or nucleotide analogue therapy experienced relapse within 4 years, according to a new study that looked at patients from 11 centers in Europe, North America, and Asia.

“We wanted to see if the patients stabilize after that year. Are they just having relapses within the first year, and then they’re inactive carriers? Especially patients who don’t achieve [hepatitis B surface antigen; HBsAg] loss. Is that mildly active disease? Would they have been better off being retreated, or are they better off [staying off] therapy? It is important to look at what happens among these patients who stop and if there is a way to tell which way they’re going to go,” said Grishma Hirode, who is a PhD candidate at the University of Toronto. Ms. Hirode presented the multinational study at the annual meeting of the American Association for the Study of Liver Diseases.

The study provided a clear picture: “They do not stabilize after 1 year. They have relapses, and these relapses aren’t mild fluctuations,” said Ms. Hirode. Another study, which was presented during the same session and investigated a national cohort in Taiwan, also found a high rate of flareups and retreatment out to 4 years.

The RETRACT-B study presented by Ms. Hirode collected data on 945 patients from 11 centers in North America, Europe, and Asia. Overall, 66% had at least one relapse within 1 year of drug withdrawal. At 2 years, 40% had a sustained remission without HBsAg loss, as had 20% at 4 years; 44% had sustained remission or HBsAg loss at 2 years, as did 30% at 4 years.

Subgroup analyses found differences between some populations: 48% of Whites and 28% of Asians had sustained remission or HBsAg loss, and 30% of Whites and 20% of Asians had sustained remission without HBsAg loss. Patients who were HBsAg positive at start of therapy were more likely to have a sustained remission or HBsAg loss (36% vs. 28%; P < .05) and to have a sustained remission without HBsAg loss (31% vs. 19%; P < .05). HBsAg levels below 100 IU/mL at cessation was also associated with a greater chance of sustained remission or HBsAg loss (58% vs. 24%; P < .05) and sustained remission without HBsAg loss (24% vs. 20%; P < .05). Not having a relapse within the first year after cessation was also associated with greater chance of sustained remission or HBsAg loss (50% versus 19%; P < .05) and sustained remission without HBsAg loss (37% vs. 13%; P < .05).

sarathsasidharan/Thinkstock

The Taiwan cohort study examined the repercussions of a government policy that limited reimbursement of nucleotide/nucleoside analogues to a fixed duration of time. Among 10,192 eligible patients, researchers at I-SHOU University found a 6.58% 4-year cumulative incidence of severe flare-ups after discontinuation (95% confidence interval, 5.91%-7.30%), defined as serum ALT levels higher than five times the upper limit of normal plus serum bilirubin levels above 2 mg/dL.

The overall incidence of flare-ups was 30.66% over 4 years (95% CI, 29.37%-31.96%). Higher risk of flareup was associated with older age (hazard ratio for each 10 years, 1.19; P<.0001), male sex (HR, 1.76; P < .0001), a diagnosis of cirrhosis (HR, 1.84; P < .0001), and a history of hepatic decompensation (HR, 1.45; P = .044).

The 4-year incidence of retreatment was 48.74% (95% CI, 46.55-50.90%)

The mortality rate was 0.63% at 4 years after a flareup (95% CI, 0.44-0.87%), and the combined rate of mortality or liver transplant was 0.79% (95% CI, 0.58-1.05%). Risk factors for higher mortality included older age (per 10 years; HR, 1.70; P < .0001), a diagnosis of cirrhosis (HR, 6.12; P < .0001), and hypertension (HR, 2.29; P = .029).
 

Selecting patients safely?

The results of both studies suggest that withdrawal from medication should be done cautiously, and patients monitored for relapse and retreatment, according to Anna Lok, MD, who was asked for comment. Dr. Lok is a professor of internal medicine, director of clinical hematology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

Between the two studies, “the message is that this approach can benefit some patients, but if the goal of treatment withdrawal is to increase the rate of hepatitis B surface antigen loss, only a small percentage of patients would benefit. Contrary to studies in Europe, the rates of HBsAg loss in studies with predominantly Asian patients are much lower,” said Dr. Lok.

The new studies provide guidance as for which patients might safely stop treatment; specifically, she suggested, young White patients who have a low HBsAg level when treatment is stopped. “But you probably shouldn’t be trying it in older Asian patients who still have high HBsAg titer, because the chance of them relapsing is very high and the chance of benefit is very low,” she said.

“One has to be very careful in selecting which patients you’re going to try this on. And if you do want to try, you’ve got to make sure that you monitor patients very carefully so treatment can be promptly resumed if necessary because some of the patients can have a severe flare and they can even develop liver failure, and this should never be tried in patients with cirrhosis” said Dr. Lok.

Ms. Hirode and Dr. Lok have no relevant financial disclosures.

More than half of chronic hepatitis B e antigen–negative patients who withdraw from nucleoside or nucleotide analogue therapy experienced relapse within 4 years, according to a new study that looked at patients from 11 centers in Europe, North America, and Asia.

“We wanted to see if the patients stabilize after that year. Are they just having relapses within the first year, and then they’re inactive carriers? Especially patients who don’t achieve [hepatitis B surface antigen; HBsAg] loss. Is that mildly active disease? Would they have been better off being retreated, or are they better off [staying off] therapy? It is important to look at what happens among these patients who stop and if there is a way to tell which way they’re going to go,” said Grishma Hirode, who is a PhD candidate at the University of Toronto. Ms. Hirode presented the multinational study at the annual meeting of the American Association for the Study of Liver Diseases.

The study provided a clear picture: “They do not stabilize after 1 year. They have relapses, and these relapses aren’t mild fluctuations,” said Ms. Hirode. Another study, which was presented during the same session and investigated a national cohort in Taiwan, also found a high rate of flareups and retreatment out to 4 years.

The RETRACT-B study presented by Ms. Hirode collected data on 945 patients from 11 centers in North America, Europe, and Asia. Overall, 66% had at least one relapse within 1 year of drug withdrawal. At 2 years, 40% had a sustained remission without HBsAg loss, as had 20% at 4 years; 44% had sustained remission or HBsAg loss at 2 years, as did 30% at 4 years.

Subgroup analyses found differences between some populations: 48% of Whites and 28% of Asians had sustained remission or HBsAg loss, and 30% of Whites and 20% of Asians had sustained remission without HBsAg loss. Patients who were HBsAg positive at start of therapy were more likely to have a sustained remission or HBsAg loss (36% vs. 28%; P < .05) and to have a sustained remission without HBsAg loss (31% vs. 19%; P < .05). HBsAg levels below 100 IU/mL at cessation was also associated with a greater chance of sustained remission or HBsAg loss (58% vs. 24%; P < .05) and sustained remission without HBsAg loss (24% vs. 20%; P < .05). Not having a relapse within the first year after cessation was also associated with greater chance of sustained remission or HBsAg loss (50% versus 19%; P < .05) and sustained remission without HBsAg loss (37% vs. 13%; P < .05).

sarathsasidharan/Thinkstock

The Taiwan cohort study examined the repercussions of a government policy that limited reimbursement of nucleotide/nucleoside analogues to a fixed duration of time. Among 10,192 eligible patients, researchers at I-SHOU University found a 6.58% 4-year cumulative incidence of severe flare-ups after discontinuation (95% confidence interval, 5.91%-7.30%), defined as serum ALT levels higher than five times the upper limit of normal plus serum bilirubin levels above 2 mg/dL.

The overall incidence of flare-ups was 30.66% over 4 years (95% CI, 29.37%-31.96%). Higher risk of flareup was associated with older age (hazard ratio for each 10 years, 1.19; P<.0001), male sex (HR, 1.76; P < .0001), a diagnosis of cirrhosis (HR, 1.84; P < .0001), and a history of hepatic decompensation (HR, 1.45; P = .044).

The 4-year incidence of retreatment was 48.74% (95% CI, 46.55-50.90%)

The mortality rate was 0.63% at 4 years after a flareup (95% CI, 0.44-0.87%), and the combined rate of mortality or liver transplant was 0.79% (95% CI, 0.58-1.05%). Risk factors for higher mortality included older age (per 10 years; HR, 1.70; P < .0001), a diagnosis of cirrhosis (HR, 6.12; P < .0001), and hypertension (HR, 2.29; P = .029).
 

Selecting patients safely?

The results of both studies suggest that withdrawal from medication should be done cautiously, and patients monitored for relapse and retreatment, according to Anna Lok, MD, who was asked for comment. Dr. Lok is a professor of internal medicine, director of clinical hematology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

Between the two studies, “the message is that this approach can benefit some patients, but if the goal of treatment withdrawal is to increase the rate of hepatitis B surface antigen loss, only a small percentage of patients would benefit. Contrary to studies in Europe, the rates of HBsAg loss in studies with predominantly Asian patients are much lower,” said Dr. Lok.

The new studies provide guidance as for which patients might safely stop treatment; specifically, she suggested, young White patients who have a low HBsAg level when treatment is stopped. “But you probably shouldn’t be trying it in older Asian patients who still have high HBsAg titer, because the chance of them relapsing is very high and the chance of benefit is very low,” she said.

“One has to be very careful in selecting which patients you’re going to try this on. And if you do want to try, you’ve got to make sure that you monitor patients very carefully so treatment can be promptly resumed if necessary because some of the patients can have a severe flare and they can even develop liver failure, and this should never be tried in patients with cirrhosis” said Dr. Lok.

Ms. Hirode and Dr. Lok have no relevant financial disclosures.

More than half of chronic hepatitis B e antigen–negative patients who withdraw from nucleoside or nucleotide analogue therapy experienced relapse within 4 years, according to a new study that looked at patients from 11 centers in Europe, North America, and Asia.

“We wanted to see if the patients stabilize after that year. Are they just having relapses within the first year, and then they’re inactive carriers? Especially patients who don’t achieve [hepatitis B surface antigen; HBsAg] loss. Is that mildly active disease? Would they have been better off being retreated, or are they better off [staying off] therapy? It is important to look at what happens among these patients who stop and if there is a way to tell which way they’re going to go,” said Grishma Hirode, who is a PhD candidate at the University of Toronto. Ms. Hirode presented the multinational study at the annual meeting of the American Association for the Study of Liver Diseases.

The study provided a clear picture: “They do not stabilize after 1 year. They have relapses, and these relapses aren’t mild fluctuations,” said Ms. Hirode. Another study, which was presented during the same session and investigated a national cohort in Taiwan, also found a high rate of flareups and retreatment out to 4 years.

The RETRACT-B study presented by Ms. Hirode collected data on 945 patients from 11 centers in North America, Europe, and Asia. Overall, 66% had at least one relapse within 1 year of drug withdrawal. At 2 years, 40% had a sustained remission without HBsAg loss, as had 20% at 4 years; 44% had sustained remission or HBsAg loss at 2 years, as did 30% at 4 years.

Subgroup analyses found differences between some populations: 48% of Whites and 28% of Asians had sustained remission or HBsAg loss, and 30% of Whites and 20% of Asians had sustained remission without HBsAg loss. Patients who were HBsAg positive at start of therapy were more likely to have a sustained remission or HBsAg loss (36% vs. 28%; P < .05) and to have a sustained remission without HBsAg loss (31% vs. 19%; P < .05). HBsAg levels below 100 IU/mL at cessation was also associated with a greater chance of sustained remission or HBsAg loss (58% vs. 24%; P < .05) and sustained remission without HBsAg loss (24% vs. 20%; P < .05). Not having a relapse within the first year after cessation was also associated with greater chance of sustained remission or HBsAg loss (50% versus 19%; P < .05) and sustained remission without HBsAg loss (37% vs. 13%; P < .05).

sarathsasidharan/Thinkstock

The Taiwan cohort study examined the repercussions of a government policy that limited reimbursement of nucleotide/nucleoside analogues to a fixed duration of time. Among 10,192 eligible patients, researchers at I-SHOU University found a 6.58% 4-year cumulative incidence of severe flare-ups after discontinuation (95% confidence interval, 5.91%-7.30%), defined as serum ALT levels higher than five times the upper limit of normal plus serum bilirubin levels above 2 mg/dL.

The overall incidence of flare-ups was 30.66% over 4 years (95% CI, 29.37%-31.96%). Higher risk of flareup was associated with older age (hazard ratio for each 10 years, 1.19; P<.0001), male sex (HR, 1.76; P < .0001), a diagnosis of cirrhosis (HR, 1.84; P < .0001), and a history of hepatic decompensation (HR, 1.45; P = .044).

The 4-year incidence of retreatment was 48.74% (95% CI, 46.55-50.90%)

The mortality rate was 0.63% at 4 years after a flareup (95% CI, 0.44-0.87%), and the combined rate of mortality or liver transplant was 0.79% (95% CI, 0.58-1.05%). Risk factors for higher mortality included older age (per 10 years; HR, 1.70; P < .0001), a diagnosis of cirrhosis (HR, 6.12; P < .0001), and hypertension (HR, 2.29; P = .029).
 

Selecting patients safely?

The results of both studies suggest that withdrawal from medication should be done cautiously, and patients monitored for relapse and retreatment, according to Anna Lok, MD, who was asked for comment. Dr. Lok is a professor of internal medicine, director of clinical hematology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

Between the two studies, “the message is that this approach can benefit some patients, but if the goal of treatment withdrawal is to increase the rate of hepatitis B surface antigen loss, only a small percentage of patients would benefit. Contrary to studies in Europe, the rates of HBsAg loss in studies with predominantly Asian patients are much lower,” said Dr. Lok.

The new studies provide guidance as for which patients might safely stop treatment; specifically, she suggested, young White patients who have a low HBsAg level when treatment is stopped. “But you probably shouldn’t be trying it in older Asian patients who still have high HBsAg titer, because the chance of them relapsing is very high and the chance of benefit is very low,” she said.

“One has to be very careful in selecting which patients you’re going to try this on. And if you do want to try, you’ve got to make sure that you monitor patients very carefully so treatment can be promptly resumed if necessary because some of the patients can have a severe flare and they can even develop liver failure, and this should never be tried in patients with cirrhosis” said Dr. Lok.

Ms. Hirode and Dr. Lok have no relevant financial disclosures.

A “virtual” liver transplant center servicing Vermont and New Hampshire has improved access to liver transplant listing among patients in rural areas of the region, according to a new analysis.

The virtual center was established in 2016 at Dartmouth Hitchcock Medical Center, and it allows patients to receive pre–liver transplant evaluations, testing, and care and posttransplant follow-up there rather than at the liver transplant center that conducts the surgery. The center includes two hepatologists, two associate care providers, and a nurse liver transplant coordinator at DHMC, and led to increased transplant listing in the vicinity, according to Margaret Liu, MD, who presented the study at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“The initiation of this Virtual Liver Transplant Center has been able to provide patients with the ability to get a full liver transplant workup and evaluation at a center near their home rather than the often time-consuming and costly process of potentially multiple trips to a liver transplant center up to 250 miles away for a full transplant evaluation,” said Dr. Liu in an interview. Dr. Liu is an internal medicine resident at Dartmouth Hitchcock Medical Center.

“Our results did show that the initiation of a virtual liver transplant center correlated with an increased and sustained liver transplant listing rate within 60 miles of Dartmouth over that particular study period. Conversely there was no significant change in the listing rate of New Hampshire zip codes that were within 60 miles of the nearest transplant center during the same study period,” said Dr. Liu.

The center receives referrals of patients who are potential candidates for liver transplant listing from practices throughout New Hampshire and Vermont, or from their own center. Their specialists conduct full testing, including a full liver transplant workup that includes evaluation of the patient’s general health and social factors, prior to sending the patient to the actual liver transplant center for their evaluation and transplant surgery. “We essentially do all of the pre–liver transplant workup, a formal liver transplant evaluation, and then the whole packet gets sent to an actual liver transplant center to expedite the process of getting listed for liver transplant. We’re able to streamline the process, so they get everything done here at a hospital near their home. If that requires multiple trips, it’s a lot more doable for the patients,” said Dr. Liu.

The researchers defined urban areas as having more than 50,000 people per square mile and within 30 miles of the nearest hospital, and rural as fewer than 10,000 and more than 60 miles from the nearest hospital. They used the Scientific Registry of Transplant Recipients to determine the number of liver transplant listings per zip code.

Between 2015 and 2019, the frequency of liver transplant listings per 10,000 people remained nearly unchanged in the metropolitan area of southern New Hampshire, ranging from around 0.36 to 0.75. In the rural area within 60 miles of DHMC, the frequency increased from about 0.7 per 10,000 in 2015 to about 1.4 in 2016 and 0.9 in 2017. There was an increase to nearly 3 in 10,000 in 2018, and the frequency was just over 2 in 2019.

The model has the potential to be used in other areas, according to Dr. Liu. “This could potentially be implemented in other rural areas that do not have a transplant center or don’t have a formal liver transplant evaluation process,” said Dr. Liu.

While other centers may have taken on some aspects of liver transplant evaluation and posttransplant care, the Virtual Liver Transplant Center is unique in that a great deal of effort has gone into covering all of a patient’s needs for the liver transplant evaluation. “It’s really the formalization that, from what I have researched, has not been done before,” said Dr. Liu.

The model addresses transplant-listing disparity, as well as improves patient quality of life through reduction in travel, according to Mayur Brahmania, MD, of Western University, London, Ont., who moderated the session. “They’ve proven that they can get more of their patients listed over the study period, which I think is amazing. The next step, I think, would be about whether getting them onto the transplant list actually made a difference in terms of outcome – looking at their wait list mortality, looking at how many of these patients actually got a liver transplantation. That’s the ultimate outcome,” said Dr. Brahmania.

He also noted the challenge of setting up a virtual center. “You have to have allied health staff – addiction counselors, physical therapists, dietitians, social workers. You need to have the appropriate ancillary services like cardiac testing, pulmonary function testing. It’s quite an endeavor, and if the program isn’t too enthusiastic or doesn’t have a local champion, it’s really hard to get something like this started off. So kudos to them for taking on this challenge and getting this up and running over the last 5 years,” said Dr. Brahmania.

Dr. Liu and Dr. Brahmania have no relevant financial disclosures.

A “virtual” liver transplant center servicing Vermont and New Hampshire has improved access to liver transplant listing among patients in rural areas of the region, according to a new analysis.

The virtual center was established in 2016 at Dartmouth Hitchcock Medical Center, and it allows patients to receive pre–liver transplant evaluations, testing, and care and posttransplant follow-up there rather than at the liver transplant center that conducts the surgery. The center includes two hepatologists, two associate care providers, and a nurse liver transplant coordinator at DHMC, and led to increased transplant listing in the vicinity, according to Margaret Liu, MD, who presented the study at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“The initiation of this Virtual Liver Transplant Center has been able to provide patients with the ability to get a full liver transplant workup and evaluation at a center near their home rather than the often time-consuming and costly process of potentially multiple trips to a liver transplant center up to 250 miles away for a full transplant evaluation,” said Dr. Liu in an interview. Dr. Liu is an internal medicine resident at Dartmouth Hitchcock Medical Center.

“Our results did show that the initiation of a virtual liver transplant center correlated with an increased and sustained liver transplant listing rate within 60 miles of Dartmouth over that particular study period. Conversely there was no significant change in the listing rate of New Hampshire zip codes that were within 60 miles of the nearest transplant center during the same study period,” said Dr. Liu.

The center receives referrals of patients who are potential candidates for liver transplant listing from practices throughout New Hampshire and Vermont, or from their own center. Their specialists conduct full testing, including a full liver transplant workup that includes evaluation of the patient’s general health and social factors, prior to sending the patient to the actual liver transplant center for their evaluation and transplant surgery. “We essentially do all of the pre–liver transplant workup, a formal liver transplant evaluation, and then the whole packet gets sent to an actual liver transplant center to expedite the process of getting listed for liver transplant. We’re able to streamline the process, so they get everything done here at a hospital near their home. If that requires multiple trips, it’s a lot more doable for the patients,” said Dr. Liu.

The researchers defined urban areas as having more than 50,000 people per square mile and within 30 miles of the nearest hospital, and rural as fewer than 10,000 and more than 60 miles from the nearest hospital. They used the Scientific Registry of Transplant Recipients to determine the number of liver transplant listings per zip code.

Between 2015 and 2019, the frequency of liver transplant listings per 10,000 people remained nearly unchanged in the metropolitan area of southern New Hampshire, ranging from around 0.36 to 0.75. In the rural area within 60 miles of DHMC, the frequency increased from about 0.7 per 10,000 in 2015 to about 1.4 in 2016 and 0.9 in 2017. There was an increase to nearly 3 in 10,000 in 2018, and the frequency was just over 2 in 2019.

The model has the potential to be used in other areas, according to Dr. Liu. “This could potentially be implemented in other rural areas that do not have a transplant center or don’t have a formal liver transplant evaluation process,” said Dr. Liu.

While other centers may have taken on some aspects of liver transplant evaluation and posttransplant care, the Virtual Liver Transplant Center is unique in that a great deal of effort has gone into covering all of a patient’s needs for the liver transplant evaluation. “It’s really the formalization that, from what I have researched, has not been done before,” said Dr. Liu.

The model addresses transplant-listing disparity, as well as improves patient quality of life through reduction in travel, according to Mayur Brahmania, MD, of Western University, London, Ont., who moderated the session. “They’ve proven that they can get more of their patients listed over the study period, which I think is amazing. The next step, I think, would be about whether getting them onto the transplant list actually made a difference in terms of outcome – looking at their wait list mortality, looking at how many of these patients actually got a liver transplantation. That’s the ultimate outcome,” said Dr. Brahmania.

He also noted the challenge of setting up a virtual center. “You have to have allied health staff – addiction counselors, physical therapists, dietitians, social workers. You need to have the appropriate ancillary services like cardiac testing, pulmonary function testing. It’s quite an endeavor, and if the program isn’t too enthusiastic or doesn’t have a local champion, it’s really hard to get something like this started off. So kudos to them for taking on this challenge and getting this up and running over the last 5 years,” said Dr. Brahmania.

Dr. Liu and Dr. Brahmania have no relevant financial disclosures.

A “virtual” liver transplant center servicing Vermont and New Hampshire has improved access to liver transplant listing among patients in rural areas of the region, according to a new analysis.

The virtual center was established in 2016 at Dartmouth Hitchcock Medical Center, and it allows patients to receive pre–liver transplant evaluations, testing, and care and posttransplant follow-up there rather than at the liver transplant center that conducts the surgery. The center includes two hepatologists, two associate care providers, and a nurse liver transplant coordinator at DHMC, and led to increased transplant listing in the vicinity, according to Margaret Liu, MD, who presented the study at the virtual annual meeting of the American Association for the Study of Liver Diseases.

“The initiation of this Virtual Liver Transplant Center has been able to provide patients with the ability to get a full liver transplant workup and evaluation at a center near their home rather than the often time-consuming and costly process of potentially multiple trips to a liver transplant center up to 250 miles away for a full transplant evaluation,” said Dr. Liu in an interview. Dr. Liu is an internal medicine resident at Dartmouth Hitchcock Medical Center.

“Our results did show that the initiation of a virtual liver transplant center correlated with an increased and sustained liver transplant listing rate within 60 miles of Dartmouth over that particular study period. Conversely there was no significant change in the listing rate of New Hampshire zip codes that were within 60 miles of the nearest transplant center during the same study period,” said Dr. Liu.

The center receives referrals of patients who are potential candidates for liver transplant listing from practices throughout New Hampshire and Vermont, or from their own center. Their specialists conduct full testing, including a full liver transplant workup that includes evaluation of the patient’s general health and social factors, prior to sending the patient to the actual liver transplant center for their evaluation and transplant surgery. “We essentially do all of the pre–liver transplant workup, a formal liver transplant evaluation, and then the whole packet gets sent to an actual liver transplant center to expedite the process of getting listed for liver transplant. We’re able to streamline the process, so they get everything done here at a hospital near their home. If that requires multiple trips, it’s a lot more doable for the patients,” said Dr. Liu.

The researchers defined urban areas as having more than 50,000 people per square mile and within 30 miles of the nearest hospital, and rural as fewer than 10,000 and more than 60 miles from the nearest hospital. They used the Scientific Registry of Transplant Recipients to determine the number of liver transplant listings per zip code.

Between 2015 and 2019, the frequency of liver transplant listings per 10,000 people remained nearly unchanged in the metropolitan area of southern New Hampshire, ranging from around 0.36 to 0.75. In the rural area within 60 miles of DHMC, the frequency increased from about 0.7 per 10,000 in 2015 to about 1.4 in 2016 and 0.9 in 2017. There was an increase to nearly 3 in 10,000 in 2018, and the frequency was just over 2 in 2019.

The model has the potential to be used in other areas, according to Dr. Liu. “This could potentially be implemented in other rural areas that do not have a transplant center or don’t have a formal liver transplant evaluation process,” said Dr. Liu.

While other centers may have taken on some aspects of liver transplant evaluation and posttransplant care, the Virtual Liver Transplant Center is unique in that a great deal of effort has gone into covering all of a patient’s needs for the liver transplant evaluation. “It’s really the formalization that, from what I have researched, has not been done before,” said Dr. Liu.

The model addresses transplant-listing disparity, as well as improves patient quality of life through reduction in travel, according to Mayur Brahmania, MD, of Western University, London, Ont., who moderated the session. “They’ve proven that they can get more of their patients listed over the study period, which I think is amazing. The next step, I think, would be about whether getting them onto the transplant list actually made a difference in terms of outcome – looking at their wait list mortality, looking at how many of these patients actually got a liver transplantation. That’s the ultimate outcome,” said Dr. Brahmania.

He also noted the challenge of setting up a virtual center. “You have to have allied health staff – addiction counselors, physical therapists, dietitians, social workers. You need to have the appropriate ancillary services like cardiac testing, pulmonary function testing. It’s quite an endeavor, and if the program isn’t too enthusiastic or doesn’t have a local champion, it’s really hard to get something like this started off. So kudos to them for taking on this challenge and getting this up and running over the last 5 years,” said Dr. Brahmania.

Dr. Liu and Dr. Brahmania have no relevant financial disclosures.

For patients with nonalcoholic fatty liver disease (NAFLD) who supplement their diets with polyunsaturated fatty acids (PUFA), liver and metabolic parameters improve, results of a systematic review and meta-analysis suggest.

Data from randomized clinical trials show that, for participants with NAFLD who used PUFA supplements with or without additional dietary interventions, hepatic steatosis and lobular inflammation decreased, and in one study, fibrosis decreased. There were also improvements in liver enzyme levels, said Saleh Alqahtani, MBChB, associate professor of medicine at Johns Hopkins University, Baltimore, during a presentation at the annual meeting of the American Association for the Study of Liver Diseases.

“Since there’s no effective medical therapy for NAFLD, weight loss through lifestyle modifications becomes the most important focused intervention for patients with NAFLD,” he said. “However, the majority of patients fail to achieve or to maintain weight loss for long-term therapy. Therefore, dietary intervention or supplementation might help reduce the prevalence of NAFLD and decrease the progression of nonalcoholic steatohepatitis [NASH] and liver cirrhosis.

“More clinical trials are warranted to determine the long-term efficacy of the Mediterranean diet and polyunsaturated fatty acid supplementation among adult patients with NAFLD,” he added.
 

RCTs and case-control studies

It’s well documented that consumption of PUFAs, found in fatty fish and in canola, grapeseed, corn, and soybean oils, as well as monounsaturated fatty acids, found in olive oil and peanut oil, can contribute to improvement of NALFD, Dr. Alqahtani said.

In contrast, foods high in saturated fatty acids, such as butter, as well as trans fats and cholesterol can contribute to NAFLD progression, he said.

In their studies of intrahepatic triglyceride content, Dr. Alqahtani and colleagues found that fatty acids in the liver come from three major sources: dietary fatty acids, which account for about 15% of liver fat, tissue lipolysis, and de novo hepatic lipogenesis.

Previous systematic reviews and meta-analyses of the relationship between diet and NAFLD have focused on marine-based (n-3) PUFAs, but “the data regarding the evidence of unsaturated fatty acids through supplements or monounsaturated fatty acids through dietary supplementation are lacking,” he said.

To summarize the effects of dietary or supplemental fatty acids on liver and metabolic parameters in adults with NAFLD, Dr. Alqahtani and colleagues conducted a systematic review and meta-analysis, concentrating on studies that included specifics about interventions and outcomes.

They identified a total of 18 randomized controlled trials and 4 case-control studies that met their criteria. The studies were published from 2008 to 2020.

Regarding the effects of interventions on the components of NASH, they found that, in 1 or more of 12 randomized trials of PUFA supplementation with or without dietary interventions, there were associations with decreased hepatic steatosis, lobular inflammation, and fibrosis and declines in ALT and AST levels.

In three trials of dietary-only interventions, there were decreases in hepatic steatosis and ALT and/or AST levels. In two studies of the effects of healthy cooking oils only, hepatic steatosis decreased, but there was no effect on ALT or AST levels.

All three interventions were associated with improvements in fasting glucose levels and insulin metabolism, as well as decreases in total cholesterol, triglycerides, and LDL cholesterol and increases in HDL cholesterol.
 

Better understanding of dietary composition

“We’ve known for a while that dietary composition may impact NAFLD and NASH,” said Manal F. Abdelmalek, MD, professor of medicine at Duke University, Durham, N.C., who commented on the study.

“What [Dr. Alqahtani and colleagues] have shown is that supplementation with healthy fatty acids improves fatty liver. This really does extend our knowledge of what we understand about dietary composition, particularly the recommendations that support higher fish consumption and a Mediterranean-style diet,” she said.

“It’s not just about the fat but the type of fat that’s consumed, and drilling down to the particulars of dietary composition beyond calories alone,” she added.

No source of funding for the study has been disclosed. Dr. Alqahtani and Dr. Abdelmalek have reported no relevant financial relationships.

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

For patients with nonalcoholic fatty liver disease (NAFLD) who supplement their diets with polyunsaturated fatty acids (PUFA), liver and metabolic parameters improve, results of a systematic review and meta-analysis suggest.

Data from randomized clinical trials show that, for participants with NAFLD who used PUFA supplements with or without additional dietary interventions, hepatic steatosis and lobular inflammation decreased, and in one study, fibrosis decreased. There were also improvements in liver enzyme levels, said Saleh Alqahtani, MBChB, associate professor of medicine at Johns Hopkins University, Baltimore, during a presentation at the annual meeting of the American Association for the Study of Liver Diseases.

“Since there’s no effective medical therapy for NAFLD, weight loss through lifestyle modifications becomes the most important focused intervention for patients with NAFLD,” he said. “However, the majority of patients fail to achieve or to maintain weight loss for long-term therapy. Therefore, dietary intervention or supplementation might help reduce the prevalence of NAFLD and decrease the progression of nonalcoholic steatohepatitis [NASH] and liver cirrhosis.

“More clinical trials are warranted to determine the long-term efficacy of the Mediterranean diet and polyunsaturated fatty acid supplementation among adult patients with NAFLD,” he added.
 

RCTs and case-control studies

It’s well documented that consumption of PUFAs, found in fatty fish and in canola, grapeseed, corn, and soybean oils, as well as monounsaturated fatty acids, found in olive oil and peanut oil, can contribute to improvement of NALFD, Dr. Alqahtani said.

In contrast, foods high in saturated fatty acids, such as butter, as well as trans fats and cholesterol can contribute to NAFLD progression, he said.

In their studies of intrahepatic triglyceride content, Dr. Alqahtani and colleagues found that fatty acids in the liver come from three major sources: dietary fatty acids, which account for about 15% of liver fat, tissue lipolysis, and de novo hepatic lipogenesis.

Previous systematic reviews and meta-analyses of the relationship between diet and NAFLD have focused on marine-based (n-3) PUFAs, but “the data regarding the evidence of unsaturated fatty acids through supplements or monounsaturated fatty acids through dietary supplementation are lacking,” he said.

To summarize the effects of dietary or supplemental fatty acids on liver and metabolic parameters in adults with NAFLD, Dr. Alqahtani and colleagues conducted a systematic review and meta-analysis, concentrating on studies that included specifics about interventions and outcomes.

They identified a total of 18 randomized controlled trials and 4 case-control studies that met their criteria. The studies were published from 2008 to 2020.

Regarding the effects of interventions on the components of NASH, they found that, in 1 or more of 12 randomized trials of PUFA supplementation with or without dietary interventions, there were associations with decreased hepatic steatosis, lobular inflammation, and fibrosis and declines in ALT and AST levels.

In three trials of dietary-only interventions, there were decreases in hepatic steatosis and ALT and/or AST levels. In two studies of the effects of healthy cooking oils only, hepatic steatosis decreased, but there was no effect on ALT or AST levels.

All three interventions were associated with improvements in fasting glucose levels and insulin metabolism, as well as decreases in total cholesterol, triglycerides, and LDL cholesterol and increases in HDL cholesterol.
 

Better understanding of dietary composition

“We’ve known for a while that dietary composition may impact NAFLD and NASH,” said Manal F. Abdelmalek, MD, professor of medicine at Duke University, Durham, N.C., who commented on the study.

“What [Dr. Alqahtani and colleagues] have shown is that supplementation with healthy fatty acids improves fatty liver. This really does extend our knowledge of what we understand about dietary composition, particularly the recommendations that support higher fish consumption and a Mediterranean-style diet,” she said.

“It’s not just about the fat but the type of fat that’s consumed, and drilling down to the particulars of dietary composition beyond calories alone,” she added.

No source of funding for the study has been disclosed. Dr. Alqahtani and Dr. Abdelmalek have reported no relevant financial relationships.

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

For patients with nonalcoholic fatty liver disease (NAFLD) who supplement their diets with polyunsaturated fatty acids (PUFA), liver and metabolic parameters improve, results of a systematic review and meta-analysis suggest.

Data from randomized clinical trials show that, for participants with NAFLD who used PUFA supplements with or without additional dietary interventions, hepatic steatosis and lobular inflammation decreased, and in one study, fibrosis decreased. There were also improvements in liver enzyme levels, said Saleh Alqahtani, MBChB, associate professor of medicine at Johns Hopkins University, Baltimore, during a presentation at the annual meeting of the American Association for the Study of Liver Diseases.

“Since there’s no effective medical therapy for NAFLD, weight loss through lifestyle modifications becomes the most important focused intervention for patients with NAFLD,” he said. “However, the majority of patients fail to achieve or to maintain weight loss for long-term therapy. Therefore, dietary intervention or supplementation might help reduce the prevalence of NAFLD and decrease the progression of nonalcoholic steatohepatitis [NASH] and liver cirrhosis.

“More clinical trials are warranted to determine the long-term efficacy of the Mediterranean diet and polyunsaturated fatty acid supplementation among adult patients with NAFLD,” he added.
 

RCTs and case-control studies

It’s well documented that consumption of PUFAs, found in fatty fish and in canola, grapeseed, corn, and soybean oils, as well as monounsaturated fatty acids, found in olive oil and peanut oil, can contribute to improvement of NALFD, Dr. Alqahtani said.

In contrast, foods high in saturated fatty acids, such as butter, as well as trans fats and cholesterol can contribute to NAFLD progression, he said.

In their studies of intrahepatic triglyceride content, Dr. Alqahtani and colleagues found that fatty acids in the liver come from three major sources: dietary fatty acids, which account for about 15% of liver fat, tissue lipolysis, and de novo hepatic lipogenesis.

Previous systematic reviews and meta-analyses of the relationship between diet and NAFLD have focused on marine-based (n-3) PUFAs, but “the data regarding the evidence of unsaturated fatty acids through supplements or monounsaturated fatty acids through dietary supplementation are lacking,” he said.

To summarize the effects of dietary or supplemental fatty acids on liver and metabolic parameters in adults with NAFLD, Dr. Alqahtani and colleagues conducted a systematic review and meta-analysis, concentrating on studies that included specifics about interventions and outcomes.

They identified a total of 18 randomized controlled trials and 4 case-control studies that met their criteria. The studies were published from 2008 to 2020.

Regarding the effects of interventions on the components of NASH, they found that, in 1 or more of 12 randomized trials of PUFA supplementation with or without dietary interventions, there were associations with decreased hepatic steatosis, lobular inflammation, and fibrosis and declines in ALT and AST levels.

In three trials of dietary-only interventions, there were decreases in hepatic steatosis and ALT and/or AST levels. In two studies of the effects of healthy cooking oils only, hepatic steatosis decreased, but there was no effect on ALT or AST levels.

All three interventions were associated with improvements in fasting glucose levels and insulin metabolism, as well as decreases in total cholesterol, triglycerides, and LDL cholesterol and increases in HDL cholesterol.
 

Better understanding of dietary composition

“We’ve known for a while that dietary composition may impact NAFLD and NASH,” said Manal F. Abdelmalek, MD, professor of medicine at Duke University, Durham, N.C., who commented on the study.

“What [Dr. Alqahtani and colleagues] have shown is that supplementation with healthy fatty acids improves fatty liver. This really does extend our knowledge of what we understand about dietary composition, particularly the recommendations that support higher fish consumption and a Mediterranean-style diet,” she said.

“It’s not just about the fat but the type of fat that’s consumed, and drilling down to the particulars of dietary composition beyond calories alone,” she added.

No source of funding for the study has been disclosed. Dr. Alqahtani and Dr. Abdelmalek have reported no relevant financial relationships.

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

Multiple comorbidities appear to worsen mortality outcomes in patients with cirrhosis: Those with compensated cirrhosis and three comorbid conditions have a mortality rate similar to patients with decompensated cirrhosis, according to a new analysis of a population-based cohort in the Dallas-Fort Worth metroplex.

“I think it’s a pretty strong message that just the presence of these chronic diseases has such a strong effect in the long run. They at least contribute to mortality to some extent. It’s really important to focus on these chronic diseases as targets early during the care that we provide to these to cirrhotic patients to make sure that we control them so that, in the long run, we can decrease the premature death and mortality in these patients,” said Mohammad Amin Fallahzadeh, MD, MPH, who presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

The study included 35,361 patients with cirrhosis. The mean age of participants was 59.5 years, 41.8% were female, 29.7% were non-White, and 17.5% were Hispanic. Comorbidities were common, occurring in about 25% of patients. Forty-five percent of comorbidities were cardiovascular diseases (CVD); 28.9% of subjects had one comorbidity, 17.5% had two comorbidities, and 12.6% had three comorbidities.

A Kaplan-Meier curve showed that patients with compensated cirrhosis and no comorbidities had the highest survival over time, while decompensated patients with comorbidities had the lowest survival (P = .01). The curve showed similar survival between patients with compensated cirrhosis and three comorbidities and decompensated patients with no comorbidities.

The risk of death increased with one comorbidity (hazard ratio, 2.5; 95% confidence interval, 2.23-2.8), two comorbidities (HR, 3.27; 95% CI, 2.9-3.69), and three comorbidities (HR, 4.52; 95% CI, 3.99-5.12).

Mortality increased with the number of comorbidities in both compensated and decompensated patients; patients with hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease; by race (White, Black, and other); and in different age groups. A stronger effect of comorbidities was seen in compensated patients (HR, 6.4 vs. 4.1), female patients (HR, 5.2 vs. 4.1), and in patients older than age 65 years (HR, 7.2 vs. 3.7 in those aged 45-64 years and 5.0 in those younger than age 45 years).

The researchers also found an apparent synergistic effect of chronic kidney disease (CKD) and CVD. Both conditions were associated with increased risk on their own, but when a patient had both CVD and CKD, mortality was higher than just the added risk of the two conditions.

The findings confirm that patients with cirrhosis and comorbidities seem to have worse quality of life and higher mortality. “I didn’t expect that it would have such a major effect, to make a compensated patient as if they are decompensated, but we definitely see that in our daily practice,” said Dr. Fallahzadeh, who is a 2nd-year internal medicine resident at Baylor University Medical Center, Dallas.

“When a hepatologist or an internist has a visit with a patient who is diagnosed with cirrhosis, they need to screen them for the other chronic diseases like diabetes, CKD, and cardiovascular disease to make sure that if they have any of these conditions, they’ll be under control, or if they need any referral for better management. For example, if they need a nephrology referral, it [should] be done as early as possible so that we can minimize the burden of these diseases in the long run for these patients. And we need to educate the patients as well about controlling these chronic problems,” said Dr. Fallahzadeh.

The findings might make researchers reconsider how to classify compensated and decompensated cirrhosis. “When we talk about decompensated liver disease, we’re talking about variceal hemorrhage, ascites, and encephalopathy. In this case, they’re saying that if you’re compensated and you [have] three of these associated medical conditions, that you could be worse off than decompensated cirrhosis. It’s really challenging the status quo and how we think about these two disease entities. They’re thought of a lot differently in terms of the mortality. That needs to be further elucidated,” said Mayur Brahmania, MD, assistant professor of medicine at Western University, London, Ont., who moderated the session.

A key limitation to the study was that the researchers did not have access to data about medication use, so it could not be determined if comorbidities were being controlled. Body mass index and most lifestyle factors were also uncontrolled.

Dr. Fallahzadeh and Dr. Brahmania have no relevant financial disclosures.

Multiple comorbidities appear to worsen mortality outcomes in patients with cirrhosis: Those with compensated cirrhosis and three comorbid conditions have a mortality rate similar to patients with decompensated cirrhosis, according to a new analysis of a population-based cohort in the Dallas-Fort Worth metroplex.

“I think it’s a pretty strong message that just the presence of these chronic diseases has such a strong effect in the long run. They at least contribute to mortality to some extent. It’s really important to focus on these chronic diseases as targets early during the care that we provide to these to cirrhotic patients to make sure that we control them so that, in the long run, we can decrease the premature death and mortality in these patients,” said Mohammad Amin Fallahzadeh, MD, MPH, who presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

The study included 35,361 patients with cirrhosis. The mean age of participants was 59.5 years, 41.8% were female, 29.7% were non-White, and 17.5% were Hispanic. Comorbidities were common, occurring in about 25% of patients. Forty-five percent of comorbidities were cardiovascular diseases (CVD); 28.9% of subjects had one comorbidity, 17.5% had two comorbidities, and 12.6% had three comorbidities.

A Kaplan-Meier curve showed that patients with compensated cirrhosis and no comorbidities had the highest survival over time, while decompensated patients with comorbidities had the lowest survival (P = .01). The curve showed similar survival between patients with compensated cirrhosis and three comorbidities and decompensated patients with no comorbidities.

The risk of death increased with one comorbidity (hazard ratio, 2.5; 95% confidence interval, 2.23-2.8), two comorbidities (HR, 3.27; 95% CI, 2.9-3.69), and three comorbidities (HR, 4.52; 95% CI, 3.99-5.12).

Mortality increased with the number of comorbidities in both compensated and decompensated patients; patients with hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease; by race (White, Black, and other); and in different age groups. A stronger effect of comorbidities was seen in compensated patients (HR, 6.4 vs. 4.1), female patients (HR, 5.2 vs. 4.1), and in patients older than age 65 years (HR, 7.2 vs. 3.7 in those aged 45-64 years and 5.0 in those younger than age 45 years).

The researchers also found an apparent synergistic effect of chronic kidney disease (CKD) and CVD. Both conditions were associated with increased risk on their own, but when a patient had both CVD and CKD, mortality was higher than just the added risk of the two conditions.

The findings confirm that patients with cirrhosis and comorbidities seem to have worse quality of life and higher mortality. “I didn’t expect that it would have such a major effect, to make a compensated patient as if they are decompensated, but we definitely see that in our daily practice,” said Dr. Fallahzadeh, who is a 2nd-year internal medicine resident at Baylor University Medical Center, Dallas.

“When a hepatologist or an internist has a visit with a patient who is diagnosed with cirrhosis, they need to screen them for the other chronic diseases like diabetes, CKD, and cardiovascular disease to make sure that if they have any of these conditions, they’ll be under control, or if they need any referral for better management. For example, if they need a nephrology referral, it [should] be done as early as possible so that we can minimize the burden of these diseases in the long run for these patients. And we need to educate the patients as well about controlling these chronic problems,” said Dr. Fallahzadeh.

The findings might make researchers reconsider how to classify compensated and decompensated cirrhosis. “When we talk about decompensated liver disease, we’re talking about variceal hemorrhage, ascites, and encephalopathy. In this case, they’re saying that if you’re compensated and you [have] three of these associated medical conditions, that you could be worse off than decompensated cirrhosis. It’s really challenging the status quo and how we think about these two disease entities. They’re thought of a lot differently in terms of the mortality. That needs to be further elucidated,” said Mayur Brahmania, MD, assistant professor of medicine at Western University, London, Ont., who moderated the session.

A key limitation to the study was that the researchers did not have access to data about medication use, so it could not be determined if comorbidities were being controlled. Body mass index and most lifestyle factors were also uncontrolled.

Dr. Fallahzadeh and Dr. Brahmania have no relevant financial disclosures.

Multiple comorbidities appear to worsen mortality outcomes in patients with cirrhosis: Those with compensated cirrhosis and three comorbid conditions have a mortality rate similar to patients with decompensated cirrhosis, according to a new analysis of a population-based cohort in the Dallas-Fort Worth metroplex.

“I think it’s a pretty strong message that just the presence of these chronic diseases has such a strong effect in the long run. They at least contribute to mortality to some extent. It’s really important to focus on these chronic diseases as targets early during the care that we provide to these to cirrhotic patients to make sure that we control them so that, in the long run, we can decrease the premature death and mortality in these patients,” said Mohammad Amin Fallahzadeh, MD, MPH, who presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

The study included 35,361 patients with cirrhosis. The mean age of participants was 59.5 years, 41.8% were female, 29.7% were non-White, and 17.5% were Hispanic. Comorbidities were common, occurring in about 25% of patients. Forty-five percent of comorbidities were cardiovascular diseases (CVD); 28.9% of subjects had one comorbidity, 17.5% had two comorbidities, and 12.6% had three comorbidities.

A Kaplan-Meier curve showed that patients with compensated cirrhosis and no comorbidities had the highest survival over time, while decompensated patients with comorbidities had the lowest survival (P = .01). The curve showed similar survival between patients with compensated cirrhosis and three comorbidities and decompensated patients with no comorbidities.

The risk of death increased with one comorbidity (hazard ratio, 2.5; 95% confidence interval, 2.23-2.8), two comorbidities (HR, 3.27; 95% CI, 2.9-3.69), and three comorbidities (HR, 4.52; 95% CI, 3.99-5.12).

Mortality increased with the number of comorbidities in both compensated and decompensated patients; patients with hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease; by race (White, Black, and other); and in different age groups. A stronger effect of comorbidities was seen in compensated patients (HR, 6.4 vs. 4.1), female patients (HR, 5.2 vs. 4.1), and in patients older than age 65 years (HR, 7.2 vs. 3.7 in those aged 45-64 years and 5.0 in those younger than age 45 years).

The researchers also found an apparent synergistic effect of chronic kidney disease (CKD) and CVD. Both conditions were associated with increased risk on their own, but when a patient had both CVD and CKD, mortality was higher than just the added risk of the two conditions.

The findings confirm that patients with cirrhosis and comorbidities seem to have worse quality of life and higher mortality. “I didn’t expect that it would have such a major effect, to make a compensated patient as if they are decompensated, but we definitely see that in our daily practice,” said Dr. Fallahzadeh, who is a 2nd-year internal medicine resident at Baylor University Medical Center, Dallas.

“When a hepatologist or an internist has a visit with a patient who is diagnosed with cirrhosis, they need to screen them for the other chronic diseases like diabetes, CKD, and cardiovascular disease to make sure that if they have any of these conditions, they’ll be under control, or if they need any referral for better management. For example, if they need a nephrology referral, it [should] be done as early as possible so that we can minimize the burden of these diseases in the long run for these patients. And we need to educate the patients as well about controlling these chronic problems,” said Dr. Fallahzadeh.

The findings might make researchers reconsider how to classify compensated and decompensated cirrhosis. “When we talk about decompensated liver disease, we’re talking about variceal hemorrhage, ascites, and encephalopathy. In this case, they’re saying that if you’re compensated and you [have] three of these associated medical conditions, that you could be worse off than decompensated cirrhosis. It’s really challenging the status quo and how we think about these two disease entities. They’re thought of a lot differently in terms of the mortality. That needs to be further elucidated,” said Mayur Brahmania, MD, assistant professor of medicine at Western University, London, Ont., who moderated the session.

A key limitation to the study was that the researchers did not have access to data about medication use, so it could not be determined if comorbidities were being controlled. Body mass index and most lifestyle factors were also uncontrolled.

Dr. Fallahzadeh and Dr. Brahmania have no relevant financial disclosures.