Liver Disease

Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.

These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.

“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”

Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.

To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
 

Human data

To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.

“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
 

Mouse data

Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.

Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.

“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”

In the meantime, the present data may steer drug development.

“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.

The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.

Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.

These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.

“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”

Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.

To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
 

Human data

To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.

“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
 

Mouse data

Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.

Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.

“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”

In the meantime, the present data may steer drug development.

“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.

The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.

Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.

These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.

“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”

Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.

To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
 

Human data

To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.

“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
 

Mouse data

Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.

Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.

“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”

In the meantime, the present data may steer drug development.

“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.

The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.

CHARLOTTE, N.C. – Metabolic and genetic risk factors for nonalcoholic fatty liver disease (NAFLD) vary across the age spectrum, but once steatosis has started, the risk of progression to cirrhosis is similar for both young and old, investigators found.

At a large Midwest medical center, younger adults were more likely than older patients to have a high-risk gene variant predisposing carriers to NAFLD. And they were less likely than their senior counterparts to have metabolic risk factors, reported Matthew J. Miller, MD, a 3rd-year resident in the department of internal medicine at the University of Michigan Hospital in Ann Arbor.

“Progression to cirrhosis was similar in patients younger than 40, compared to older patients, suggesting NAFLD in the young should not be considered more benign than in older patients,” he said in an oral abstract presented at the annual meeting of the American College of Gastroenterology.

MDedge News/Neil Osterweil

The prevalence of NAFLD among younger adults is increasing, but it’s still unknown whether the course of NAFLD is more benign in these patients than in older adults.

In addition, the rate of progression to cirrhosis in patients with NAFLD can vary, making it difficult to predict those patients most at risk for advanced liver disease, Dr. Miller said.

He and his colleagues sought to characterize genetic and metabolic risk factors for NAFLD and their effects on disease progression in patients from 18 to 40 years, 40 to 59 years, and 60 and older.

The investigators collected data on patients with documented objective evidence of NAFLD seen at the Michigan Medicine health care system from 2010 through 2021.

They identified NAFLD by hepatic steatosis on imaging, biopsy, or transient elastography in the absence of other chronic liver diseases, with the earliest date of a hepatic steatosis diagnosis determined to be the index date.

The investigators determined the presence of cirrhosis using validated International Classification of Diseases version 9 or 10 codes, with incident cirrhosis defined as any new cirrhosis diagnosis at least 1 year after the index date.

They also looked at the frequency of known NAFLD risk alleles in a subset of patients with available genetic data.

They divided 31,505 patients into three age groups for comparison: 8,252 patients age 18-39 at the time of steatosis identification, 15,035 age 40-59, and 8,218 age 60 or older.

Of the full cohort, 804 had cirrhosis at the index date, and 388 others developed incident cirrhosis during 128,090 person-years of follow-up.

The prevalence of hypertension, hyperlipidemia, and diabetes were significantly lower in the youngest group, compared with the two older groups, but the youngest patients had a higher prevalence of obesity than the other two groups, with a significantly higher prevalence of class 3 (morbid) obesity.

Of the 4,359 patients with genetic data available, the NAFLD-promoting PNPLA3-rs738409-G allele was more common in the young, compared with the other two age groups (P = .016).

When the investigators looked at the ability of three laboratory tests – the AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB4), and NAFLD fibrosis score for identifying prevalent cirrhosis – they found that the scores performed similarly for patients in the 40-59 group, but the NFS did less well among patients in the 18-39 group. There were no significant differences among the three age groups in the risk for incident cirrhosis over 10 years.

The study helps to answer some of the questions surrounding differences in risk factors across the age spectrum, commented Patricia Jones, MD, MSCR, from the University of Miami.

“We wonder how these people with fatty liver are different. Do younger people have a more malignant course? Are they going to progress more rapidly than others, or not? Because if you think of a disease like fatty liver or for that matter any metabolic syndrome–based disease, it’s a spectrum and a continuum, and by the time you’re diagnosed you’ve already had that condition, so it’s really more interesting to me when people are diagnosed, because diagnosing at a younger age allows you to intervene earlier,” she said in an interview.

Dr. Jones said that she was also interested in exploring how the genetic data might be used to improve care for patients, perhaps by testing for the high-risk allele in routine clinical practice.

“It will be interesting to see how people with this allele progress, independently of whether they’re diagnosed at 40, 50, or 60,” she said.

Dr. Jones was a moderator of the session where Dr. Williams presented his data.

Comoderator Mitchell A. Mah’moud, MD, FACG from Duke University in Durham, N.C., commented in an interview that, “with the medications we have available, maybe we can target these patients and prevent progression to cirrhosis and some of the decompensation that we see.”

The study authors did not disclose a funding source. Dr. Miller, Dr. Jones, and Dr. Mah’moud all reported having no relevant financial disclosures.

CHARLOTTE, N.C. – Metabolic and genetic risk factors for nonalcoholic fatty liver disease (NAFLD) vary across the age spectrum, but once steatosis has started, the risk of progression to cirrhosis is similar for both young and old, investigators found.

At a large Midwest medical center, younger adults were more likely than older patients to have a high-risk gene variant predisposing carriers to NAFLD. And they were less likely than their senior counterparts to have metabolic risk factors, reported Matthew J. Miller, MD, a 3rd-year resident in the department of internal medicine at the University of Michigan Hospital in Ann Arbor.

“Progression to cirrhosis was similar in patients younger than 40, compared to older patients, suggesting NAFLD in the young should not be considered more benign than in older patients,” he said in an oral abstract presented at the annual meeting of the American College of Gastroenterology.

MDedge News/Neil Osterweil

The prevalence of NAFLD among younger adults is increasing, but it’s still unknown whether the course of NAFLD is more benign in these patients than in older adults.

In addition, the rate of progression to cirrhosis in patients with NAFLD can vary, making it difficult to predict those patients most at risk for advanced liver disease, Dr. Miller said.

He and his colleagues sought to characterize genetic and metabolic risk factors for NAFLD and their effects on disease progression in patients from 18 to 40 years, 40 to 59 years, and 60 and older.

The investigators collected data on patients with documented objective evidence of NAFLD seen at the Michigan Medicine health care system from 2010 through 2021.

They identified NAFLD by hepatic steatosis on imaging, biopsy, or transient elastography in the absence of other chronic liver diseases, with the earliest date of a hepatic steatosis diagnosis determined to be the index date.

The investigators determined the presence of cirrhosis using validated International Classification of Diseases version 9 or 10 codes, with incident cirrhosis defined as any new cirrhosis diagnosis at least 1 year after the index date.

They also looked at the frequency of known NAFLD risk alleles in a subset of patients with available genetic data.

They divided 31,505 patients into three age groups for comparison: 8,252 patients age 18-39 at the time of steatosis identification, 15,035 age 40-59, and 8,218 age 60 or older.

Of the full cohort, 804 had cirrhosis at the index date, and 388 others developed incident cirrhosis during 128,090 person-years of follow-up.

The prevalence of hypertension, hyperlipidemia, and diabetes were significantly lower in the youngest group, compared with the two older groups, but the youngest patients had a higher prevalence of obesity than the other two groups, with a significantly higher prevalence of class 3 (morbid) obesity.

Of the 4,359 patients with genetic data available, the NAFLD-promoting PNPLA3-rs738409-G allele was more common in the young, compared with the other two age groups (P = .016).

When the investigators looked at the ability of three laboratory tests – the AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB4), and NAFLD fibrosis score for identifying prevalent cirrhosis – they found that the scores performed similarly for patients in the 40-59 group, but the NFS did less well among patients in the 18-39 group. There were no significant differences among the three age groups in the risk for incident cirrhosis over 10 years.

The study helps to answer some of the questions surrounding differences in risk factors across the age spectrum, commented Patricia Jones, MD, MSCR, from the University of Miami.

“We wonder how these people with fatty liver are different. Do younger people have a more malignant course? Are they going to progress more rapidly than others, or not? Because if you think of a disease like fatty liver or for that matter any metabolic syndrome–based disease, it’s a spectrum and a continuum, and by the time you’re diagnosed you’ve already had that condition, so it’s really more interesting to me when people are diagnosed, because diagnosing at a younger age allows you to intervene earlier,” she said in an interview.

Dr. Jones said that she was also interested in exploring how the genetic data might be used to improve care for patients, perhaps by testing for the high-risk allele in routine clinical practice.

“It will be interesting to see how people with this allele progress, independently of whether they’re diagnosed at 40, 50, or 60,” she said.

Dr. Jones was a moderator of the session where Dr. Williams presented his data.

Comoderator Mitchell A. Mah’moud, MD, FACG from Duke University in Durham, N.C., commented in an interview that, “with the medications we have available, maybe we can target these patients and prevent progression to cirrhosis and some of the decompensation that we see.”

The study authors did not disclose a funding source. Dr. Miller, Dr. Jones, and Dr. Mah’moud all reported having no relevant financial disclosures.

CHARLOTTE, N.C. – Metabolic and genetic risk factors for nonalcoholic fatty liver disease (NAFLD) vary across the age spectrum, but once steatosis has started, the risk of progression to cirrhosis is similar for both young and old, investigators found.

At a large Midwest medical center, younger adults were more likely than older patients to have a high-risk gene variant predisposing carriers to NAFLD. And they were less likely than their senior counterparts to have metabolic risk factors, reported Matthew J. Miller, MD, a 3rd-year resident in the department of internal medicine at the University of Michigan Hospital in Ann Arbor.

“Progression to cirrhosis was similar in patients younger than 40, compared to older patients, suggesting NAFLD in the young should not be considered more benign than in older patients,” he said in an oral abstract presented at the annual meeting of the American College of Gastroenterology.

MDedge News/Neil Osterweil

The prevalence of NAFLD among younger adults is increasing, but it’s still unknown whether the course of NAFLD is more benign in these patients than in older adults.

In addition, the rate of progression to cirrhosis in patients with NAFLD can vary, making it difficult to predict those patients most at risk for advanced liver disease, Dr. Miller said.

He and his colleagues sought to characterize genetic and metabolic risk factors for NAFLD and their effects on disease progression in patients from 18 to 40 years, 40 to 59 years, and 60 and older.

The investigators collected data on patients with documented objective evidence of NAFLD seen at the Michigan Medicine health care system from 2010 through 2021.

They identified NAFLD by hepatic steatosis on imaging, biopsy, or transient elastography in the absence of other chronic liver diseases, with the earliest date of a hepatic steatosis diagnosis determined to be the index date.

The investigators determined the presence of cirrhosis using validated International Classification of Diseases version 9 or 10 codes, with incident cirrhosis defined as any new cirrhosis diagnosis at least 1 year after the index date.

They also looked at the frequency of known NAFLD risk alleles in a subset of patients with available genetic data.

They divided 31,505 patients into three age groups for comparison: 8,252 patients age 18-39 at the time of steatosis identification, 15,035 age 40-59, and 8,218 age 60 or older.

Of the full cohort, 804 had cirrhosis at the index date, and 388 others developed incident cirrhosis during 128,090 person-years of follow-up.

The prevalence of hypertension, hyperlipidemia, and diabetes were significantly lower in the youngest group, compared with the two older groups, but the youngest patients had a higher prevalence of obesity than the other two groups, with a significantly higher prevalence of class 3 (morbid) obesity.

Of the 4,359 patients with genetic data available, the NAFLD-promoting PNPLA3-rs738409-G allele was more common in the young, compared with the other two age groups (P = .016).

When the investigators looked at the ability of three laboratory tests – the AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB4), and NAFLD fibrosis score for identifying prevalent cirrhosis – they found that the scores performed similarly for patients in the 40-59 group, but the NFS did less well among patients in the 18-39 group. There were no significant differences among the three age groups in the risk for incident cirrhosis over 10 years.

The study helps to answer some of the questions surrounding differences in risk factors across the age spectrum, commented Patricia Jones, MD, MSCR, from the University of Miami.

“We wonder how these people with fatty liver are different. Do younger people have a more malignant course? Are they going to progress more rapidly than others, or not? Because if you think of a disease like fatty liver or for that matter any metabolic syndrome–based disease, it’s a spectrum and a continuum, and by the time you’re diagnosed you’ve already had that condition, so it’s really more interesting to me when people are diagnosed, because diagnosing at a younger age allows you to intervene earlier,” she said in an interview.

Dr. Jones said that she was also interested in exploring how the genetic data might be used to improve care for patients, perhaps by testing for the high-risk allele in routine clinical practice.

“It will be interesting to see how people with this allele progress, independently of whether they’re diagnosed at 40, 50, or 60,” she said.

Dr. Jones was a moderator of the session where Dr. Williams presented his data.

Comoderator Mitchell A. Mah’moud, MD, FACG from Duke University in Durham, N.C., commented in an interview that, “with the medications we have available, maybe we can target these patients and prevent progression to cirrhosis and some of the decompensation that we see.”

The study authors did not disclose a funding source. Dr. Miller, Dr. Jones, and Dr. Mah’moud all reported having no relevant financial disclosures.

In a subgroup of patients with hepatorenal syndrome type 1 (HRS) who received a liver transplant, terlipressin treatment appears to reduce the need for renal replacement therapy (RRT) through 12 months of follow-up, according to a study presented at the annual meeting of the American College of Gastroenterology.

Among transplant recipients, overall 12-month survival was 11% higher for those treated with terlipressin compared with placebo, said K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the University of Pennsylvania, Philadelphia.

“Hepatorenal syndrome type 1 is a potentially reversible form of acute kidney injury that occurs in the setting of end-stage liver disease,” he said.

Liver transplantation, which eliminates end-stage liver disease, is the only definitive treatment for HRS. However, renal replacement therapy is common and associated with poor clinical outcomes and low patient survival rates in both the pretransplant and posttransplant settings, he noted.

Terlipressin, an injectable synthetic vasopressin analogue, restores renal blood flow and reverses HRS in 20%-40% of patients, Dr. Reddy said. In September, the U.S. Food and Drug Administration approved terlipressin (Terlivaz) for patients with HRS type 1. The label has a boxed warning for serious or fatal respiratory failure.

The safety and efficacy were assessed in the phase 3 CONFIRM trial, which Dr. Reddy and colleagues previously published. The randomized, placebo-controlled study demonstrated that terlipressin reversed HRS and reduced the need for RRT through day 30. The reversal of HRS with terlipressin did not improve 90-day survival as compared with placebo, which researchers attributed to a higher death rate within 90 days after the first dose despite improved kidney function.

A closer look at the liver transplant patients

In the subgroup analysis of the CONFIRM study, Dr. Reddy and colleagues analyzed the clinical outcomes through 12 months of follow-up in patients with HRS who received a liver transplant. They looked at the incidence of verified HRS reversal, HRS reversal, need for RRT, and overall survival.

Verified HRS reversal was defined as two consecutive serum creatinine measurements of 1.5 mg/dL or less at least 2 hours apart up to day 14 and survival without RRT for at least 10 days. HRS reversal was defined as a serum creatinine level of 1.5 mg/dL or less while on treatment. In addition, the need for RRT and overall survival were assessed at days 30, 60, 90, 180, and 365.

RRT was defined as any procedure that replaced nonendocrine kidney function, including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques.

In the CONFIRM study, 199 patients with HRS were treated with terlipressin plus albumin, and 101 patients were treated with placebo plus albumin for up to 14 days. In the terlipressin group, 46 patients received liver transplants within the first 2 months of the study, as did 29 in the placebo group. Two patients in the terlipressin group and one in the placebo group received a simultaneous liver-kidney transplant.
 

Meaningful clinical outcomes

In the 12-month follow-up subgroup analysis, verified HRS reversal was statistically comparable between the groups, with a 30% decrease in the terlipressin group and 17% decrease in the placebo group, Dr. Reddy reported.

HRS reversal was higher in the terlipressin group, at 37%, as compared with 14% in the placebo group.

The pretransplant need for RRT was lower in the terlipressin group, at 30%, as compared with 62% in the placebo group. The posttransplant need for RRT remained numerically lower in the terlipressin group at all time points and was significantly lower at day 180 and day 365.

Overall survival for transplant recipients in the terlipressin group was 94%, as compared with 83% in the placebo group. Posttreatment adverse events and severe adverse events were similar between the groups.

“Collectively, these data indicate that terlipressin treatment in patients with HRS led to better long-term clinical outcomes in those who received a liver transplant,” Dr. Reddy said.

The study was funded by Mallinckrodt Pharmaceuticals, which manufactures terlipressin. One author is an employee of Mallinckrodt, and the other authors have served in an advisory role or received grant support from Mallinckrodt. The authors also disclosed consultant roles and research support from several other pharmaceutical companies.

In a subgroup of patients with hepatorenal syndrome type 1 (HRS) who received a liver transplant, terlipressin treatment appears to reduce the need for renal replacement therapy (RRT) through 12 months of follow-up, according to a study presented at the annual meeting of the American College of Gastroenterology.

Among transplant recipients, overall 12-month survival was 11% higher for those treated with terlipressin compared with placebo, said K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the University of Pennsylvania, Philadelphia.

“Hepatorenal syndrome type 1 is a potentially reversible form of acute kidney injury that occurs in the setting of end-stage liver disease,” he said.

Liver transplantation, which eliminates end-stage liver disease, is the only definitive treatment for HRS. However, renal replacement therapy is common and associated with poor clinical outcomes and low patient survival rates in both the pretransplant and posttransplant settings, he noted.

Terlipressin, an injectable synthetic vasopressin analogue, restores renal blood flow and reverses HRS in 20%-40% of patients, Dr. Reddy said. In September, the U.S. Food and Drug Administration approved terlipressin (Terlivaz) for patients with HRS type 1. The label has a boxed warning for serious or fatal respiratory failure.

The safety and efficacy were assessed in the phase 3 CONFIRM trial, which Dr. Reddy and colleagues previously published. The randomized, placebo-controlled study demonstrated that terlipressin reversed HRS and reduced the need for RRT through day 30. The reversal of HRS with terlipressin did not improve 90-day survival as compared with placebo, which researchers attributed to a higher death rate within 90 days after the first dose despite improved kidney function.

A closer look at the liver transplant patients

In the subgroup analysis of the CONFIRM study, Dr. Reddy and colleagues analyzed the clinical outcomes through 12 months of follow-up in patients with HRS who received a liver transplant. They looked at the incidence of verified HRS reversal, HRS reversal, need for RRT, and overall survival.

Verified HRS reversal was defined as two consecutive serum creatinine measurements of 1.5 mg/dL or less at least 2 hours apart up to day 14 and survival without RRT for at least 10 days. HRS reversal was defined as a serum creatinine level of 1.5 mg/dL or less while on treatment. In addition, the need for RRT and overall survival were assessed at days 30, 60, 90, 180, and 365.

RRT was defined as any procedure that replaced nonendocrine kidney function, including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques.

In the CONFIRM study, 199 patients with HRS were treated with terlipressin plus albumin, and 101 patients were treated with placebo plus albumin for up to 14 days. In the terlipressin group, 46 patients received liver transplants within the first 2 months of the study, as did 29 in the placebo group. Two patients in the terlipressin group and one in the placebo group received a simultaneous liver-kidney transplant.
 

Meaningful clinical outcomes

In the 12-month follow-up subgroup analysis, verified HRS reversal was statistically comparable between the groups, with a 30% decrease in the terlipressin group and 17% decrease in the placebo group, Dr. Reddy reported.

HRS reversal was higher in the terlipressin group, at 37%, as compared with 14% in the placebo group.

The pretransplant need for RRT was lower in the terlipressin group, at 30%, as compared with 62% in the placebo group. The posttransplant need for RRT remained numerically lower in the terlipressin group at all time points and was significantly lower at day 180 and day 365.

Overall survival for transplant recipients in the terlipressin group was 94%, as compared with 83% in the placebo group. Posttreatment adverse events and severe adverse events were similar between the groups.

“Collectively, these data indicate that terlipressin treatment in patients with HRS led to better long-term clinical outcomes in those who received a liver transplant,” Dr. Reddy said.

The study was funded by Mallinckrodt Pharmaceuticals, which manufactures terlipressin. One author is an employee of Mallinckrodt, and the other authors have served in an advisory role or received grant support from Mallinckrodt. The authors also disclosed consultant roles and research support from several other pharmaceutical companies.

In a subgroup of patients with hepatorenal syndrome type 1 (HRS) who received a liver transplant, terlipressin treatment appears to reduce the need for renal replacement therapy (RRT) through 12 months of follow-up, according to a study presented at the annual meeting of the American College of Gastroenterology.

Among transplant recipients, overall 12-month survival was 11% higher for those treated with terlipressin compared with placebo, said K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the University of Pennsylvania, Philadelphia.

“Hepatorenal syndrome type 1 is a potentially reversible form of acute kidney injury that occurs in the setting of end-stage liver disease,” he said.

Liver transplantation, which eliminates end-stage liver disease, is the only definitive treatment for HRS. However, renal replacement therapy is common and associated with poor clinical outcomes and low patient survival rates in both the pretransplant and posttransplant settings, he noted.

Terlipressin, an injectable synthetic vasopressin analogue, restores renal blood flow and reverses HRS in 20%-40% of patients, Dr. Reddy said. In September, the U.S. Food and Drug Administration approved terlipressin (Terlivaz) for patients with HRS type 1. The label has a boxed warning for serious or fatal respiratory failure.

The safety and efficacy were assessed in the phase 3 CONFIRM trial, which Dr. Reddy and colleagues previously published. The randomized, placebo-controlled study demonstrated that terlipressin reversed HRS and reduced the need for RRT through day 30. The reversal of HRS with terlipressin did not improve 90-day survival as compared with placebo, which researchers attributed to a higher death rate within 90 days after the first dose despite improved kidney function.

A closer look at the liver transplant patients

In the subgroup analysis of the CONFIRM study, Dr. Reddy and colleagues analyzed the clinical outcomes through 12 months of follow-up in patients with HRS who received a liver transplant. They looked at the incidence of verified HRS reversal, HRS reversal, need for RRT, and overall survival.

Verified HRS reversal was defined as two consecutive serum creatinine measurements of 1.5 mg/dL or less at least 2 hours apart up to day 14 and survival without RRT for at least 10 days. HRS reversal was defined as a serum creatinine level of 1.5 mg/dL or less while on treatment. In addition, the need for RRT and overall survival were assessed at days 30, 60, 90, 180, and 365.

RRT was defined as any procedure that replaced nonendocrine kidney function, including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques.

In the CONFIRM study, 199 patients with HRS were treated with terlipressin plus albumin, and 101 patients were treated with placebo plus albumin for up to 14 days. In the terlipressin group, 46 patients received liver transplants within the first 2 months of the study, as did 29 in the placebo group. Two patients in the terlipressin group and one in the placebo group received a simultaneous liver-kidney transplant.
 

Meaningful clinical outcomes

In the 12-month follow-up subgroup analysis, verified HRS reversal was statistically comparable between the groups, with a 30% decrease in the terlipressin group and 17% decrease in the placebo group, Dr. Reddy reported.

HRS reversal was higher in the terlipressin group, at 37%, as compared with 14% in the placebo group.

The pretransplant need for RRT was lower in the terlipressin group, at 30%, as compared with 62% in the placebo group. The posttransplant need for RRT remained numerically lower in the terlipressin group at all time points and was significantly lower at day 180 and day 365.

Overall survival for transplant recipients in the terlipressin group was 94%, as compared with 83% in the placebo group. Posttreatment adverse events and severe adverse events were similar between the groups.

“Collectively, these data indicate that terlipressin treatment in patients with HRS led to better long-term clinical outcomes in those who received a liver transplant,” Dr. Reddy said.

The study was funded by Mallinckrodt Pharmaceuticals, which manufactures terlipressin. One author is an employee of Mallinckrodt, and the other authors have served in an advisory role or received grant support from Mallinckrodt. The authors also disclosed consultant roles and research support from several other pharmaceutical companies.

The COVID-19 pandemic fueled a sharp uptick in deaths related to chronic liver disease and cirrhosis among people with diabetes, largely owing to nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), new data show.

“Our observations confirm that COVID-19 had a higher likelihood of impacting vulnerable populations with pre-existing chronic liver diseases and diabetes, with a death rate as high as 10% in individuals with co-existing chronic liver disease and diabetes,” write the authors.

“The inability to attend regular outpatient clinics for close monitoring and treatment accompanied by diversion of health care resources to COVID-19 care may have resulted in the suboptimal or delayed clinical care of individuals with diabetes and chronic liver disease during the COVID-19 pandemic,” they add.

Donghee Kim, MD, PhD, with the Division of Gastroenterology and Hepatology, Stanford (Calif.) University School of Medicine, and colleagues report their findings in the journal Digestive and Liver Disease.
 

Vulnerable group

The researchers used U.S. national mortality data (2017-2020) to estimate chronic liver disease–related mortality trends among individuals with diabetes before and during the COVID-19 pandemic.

Before the pandemic, the quarterly mortality for chronic liver disease remained stable (quarterly percentage change, 0.6%) but then sharply increased during the pandemic (QPC, 8.6%).

A similar trend was seen with cirrhosis-related mortality (QPC, 0.3% before the pandemic vs. 8.4% during the pandemic).

NAFLD and ALD mortality among individuals with diabetes was steadily increasing before the pandemic (QPC, 4.2% and 3.5%, respectively) but showed a more rapid increase during the pandemic (QPC, 9.6% and 7.7%, respectively).

ALD-related mortality in men was more than threefold higher than in women, while NAFLD-related mortality in women was more than twofold higher than in men.

Mortality for hepatitis C virus infection declined before the pandemic (QPC, −3.3%) and remained stable during the pandemic.

COVID-19–related mortality among adults with chronic liver disease and diabetes also rose sharply during the pandemic – from 0.4% in the first quarter of 2020 to 12.9% in the last quarter of 2020 – with no considerable difference between men and women.
 

Blame it on lockdowns?

Dr. Kim and colleagues say research is needed to better understand the direct and indirect influence of COVID-19 on coexisting chronic liver disease and diabetes.

“It is plausible that psychosocial stress and a higher predisposition to psychiatric disorders during the COVID-19 pandemic can increase the risk of alcohol use disorder and ALD,” they write.

“Furthermore, it is prudent to suspect that COVID-19–related lockdowns may increase the risk of obesity, leading to a higher risk of insulin resistance and metabolic complications, including diabetes and NAFLD. Future studies are needed to improve our understanding of these possible pathogenetic links. More importantly, emergency preparedness or contingency plans must be in place to continue and provide uninterrupted care for chronic ailments during times of disaster,” they add.

The study had no specific funding. The authors report no relevant financial relationships.

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

The COVID-19 pandemic fueled a sharp uptick in deaths related to chronic liver disease and cirrhosis among people with diabetes, largely owing to nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), new data show.

“Our observations confirm that COVID-19 had a higher likelihood of impacting vulnerable populations with pre-existing chronic liver diseases and diabetes, with a death rate as high as 10% in individuals with co-existing chronic liver disease and diabetes,” write the authors.

“The inability to attend regular outpatient clinics for close monitoring and treatment accompanied by diversion of health care resources to COVID-19 care may have resulted in the suboptimal or delayed clinical care of individuals with diabetes and chronic liver disease during the COVID-19 pandemic,” they add.

Donghee Kim, MD, PhD, with the Division of Gastroenterology and Hepatology, Stanford (Calif.) University School of Medicine, and colleagues report their findings in the journal Digestive and Liver Disease.
 

Vulnerable group

The researchers used U.S. national mortality data (2017-2020) to estimate chronic liver disease–related mortality trends among individuals with diabetes before and during the COVID-19 pandemic.

Before the pandemic, the quarterly mortality for chronic liver disease remained stable (quarterly percentage change, 0.6%) but then sharply increased during the pandemic (QPC, 8.6%).

A similar trend was seen with cirrhosis-related mortality (QPC, 0.3% before the pandemic vs. 8.4% during the pandemic).

NAFLD and ALD mortality among individuals with diabetes was steadily increasing before the pandemic (QPC, 4.2% and 3.5%, respectively) but showed a more rapid increase during the pandemic (QPC, 9.6% and 7.7%, respectively).

ALD-related mortality in men was more than threefold higher than in women, while NAFLD-related mortality in women was more than twofold higher than in men.

Mortality for hepatitis C virus infection declined before the pandemic (QPC, −3.3%) and remained stable during the pandemic.

COVID-19–related mortality among adults with chronic liver disease and diabetes also rose sharply during the pandemic – from 0.4% in the first quarter of 2020 to 12.9% in the last quarter of 2020 – with no considerable difference between men and women.
 

Blame it on lockdowns?

Dr. Kim and colleagues say research is needed to better understand the direct and indirect influence of COVID-19 on coexisting chronic liver disease and diabetes.

“It is plausible that psychosocial stress and a higher predisposition to psychiatric disorders during the COVID-19 pandemic can increase the risk of alcohol use disorder and ALD,” they write.

“Furthermore, it is prudent to suspect that COVID-19–related lockdowns may increase the risk of obesity, leading to a higher risk of insulin resistance and metabolic complications, including diabetes and NAFLD. Future studies are needed to improve our understanding of these possible pathogenetic links. More importantly, emergency preparedness or contingency plans must be in place to continue and provide uninterrupted care for chronic ailments during times of disaster,” they add.

The study had no specific funding. The authors report no relevant financial relationships.

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

The COVID-19 pandemic fueled a sharp uptick in deaths related to chronic liver disease and cirrhosis among people with diabetes, largely owing to nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), new data show.

“Our observations confirm that COVID-19 had a higher likelihood of impacting vulnerable populations with pre-existing chronic liver diseases and diabetes, with a death rate as high as 10% in individuals with co-existing chronic liver disease and diabetes,” write the authors.

“The inability to attend regular outpatient clinics for close monitoring and treatment accompanied by diversion of health care resources to COVID-19 care may have resulted in the suboptimal or delayed clinical care of individuals with diabetes and chronic liver disease during the COVID-19 pandemic,” they add.

Donghee Kim, MD, PhD, with the Division of Gastroenterology and Hepatology, Stanford (Calif.) University School of Medicine, and colleagues report their findings in the journal Digestive and Liver Disease.
 

Vulnerable group

The researchers used U.S. national mortality data (2017-2020) to estimate chronic liver disease–related mortality trends among individuals with diabetes before and during the COVID-19 pandemic.

Before the pandemic, the quarterly mortality for chronic liver disease remained stable (quarterly percentage change, 0.6%) but then sharply increased during the pandemic (QPC, 8.6%).

A similar trend was seen with cirrhosis-related mortality (QPC, 0.3% before the pandemic vs. 8.4% during the pandemic).

NAFLD and ALD mortality among individuals with diabetes was steadily increasing before the pandemic (QPC, 4.2% and 3.5%, respectively) but showed a more rapid increase during the pandemic (QPC, 9.6% and 7.7%, respectively).

ALD-related mortality in men was more than threefold higher than in women, while NAFLD-related mortality in women was more than twofold higher than in men.

Mortality for hepatitis C virus infection declined before the pandemic (QPC, −3.3%) and remained stable during the pandemic.

COVID-19–related mortality among adults with chronic liver disease and diabetes also rose sharply during the pandemic – from 0.4% in the first quarter of 2020 to 12.9% in the last quarter of 2020 – with no considerable difference between men and women.
 

Blame it on lockdowns?

Dr. Kim and colleagues say research is needed to better understand the direct and indirect influence of COVID-19 on coexisting chronic liver disease and diabetes.

“It is plausible that psychosocial stress and a higher predisposition to psychiatric disorders during the COVID-19 pandemic can increase the risk of alcohol use disorder and ALD,” they write.

“Furthermore, it is prudent to suspect that COVID-19–related lockdowns may increase the risk of obesity, leading to a higher risk of insulin resistance and metabolic complications, including diabetes and NAFLD. Future studies are needed to improve our understanding of these possible pathogenetic links. More importantly, emergency preparedness or contingency plans must be in place to continue and provide uninterrupted care for chronic ailments during times of disaster,” they add.

The study had no specific funding. The authors report no relevant financial relationships.

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

Acute kidney injury (AKI) in patients with cirrhosis is potentially preventable, and there are clear steps that can be taken to manage and reverse the condition, concludes a clinical practice update from the American Gastroenterological Association.

AKI occurs in 47% of patients hospitalized with complications of cirrhosis and in approximately 30% of outpatients with cirrhosis, resulting in a total cost in the United States of $4 billion, explained Patrick S. Kamath, MD, division of gastroenterology and hepatology, Mayo Medical School, Rochester, Minn., one of the authors of this update.

Moreover, Dr. Kamath told this news organization, among patients with cirrhosis and AKI, morbidity and mortality is sevenfold higher in comparison to those without cirrhosis, and repeated episodes of AKI increase the risk of progression to chronic kidney disease.

To provide practical advice for the clinical management of patients with cirrhosis and AKI, the authors conducted an expert review of the best available published evidence and gathered expert opinion.

The update was published online in Clinical Gastroenterology and Hepatology.
 

Some key takeaways

Among its 14 best practice statements, it describes three situations indicative of AKI:

• A serum creatinine increase of 0.3 mg/dL or more within 48 hours, or
• A serum creatinine increase of 50% or more from baseline, which is a stable serum creatinine in the past 3 months.
• Reduction in urine output of up to 0.5 mL/kg per hour for more than 6 hours.

The update also emphasizes the importance of an accurate diagnosis, inasmuch as not all cases of AKI are due to hepatorenal syndrome (HRS), for example. It goes on to advise that the specific type of AKI be identified through medical history and physical examination, as well as with blood biochemistry, urine microscopic examination, urine chemistry, selected urinary biomarkers, and renal ultrasound.

Additionally, it underscores the need to identify and treat infections and to closely monitor fluid status.

Nancy S. Reau, MD, Rush Medical College, Chicago, who was not involved in the update, commented to this news organization that fluid status is important when giving albumin replacement therapy because of the increased risk for pulmonary edema.

She also highlighted that this update advises against transjugular intrahepatic portosystemic shunts (TIPSs) as a specific treatment for HRS-AKI, noting that, although the 2022 North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension do not advocate for TIPS for this indication, they also indicated that there was enough evidence to advise against it.

In other key best practice advice statements, the update advises clinicians to hold diuretics and nonselective beta blockers and to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs).
 

‘Timely’ update

Overall, Dr. Reau believes that the update is “timely, especially in light of the recent [U.S.] approval of terlipressin, which will change our treatment options.”

This update also supports the American Association for the Study of Liver Diseases (AASLD) 2021 Practice Guidance guidelines on HRS, she added.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., who was not involved in writing the update, told this news organization that the document is important because of the huge increase in mortality among patients with cirrhosis and AKI.

He commented that there has been much advancement in understanding the condition, with updated nomenclature and novel medical treatments, and that this makes the update timely.

Moreover, the update will help clinicians who are involved in the care of patients with cirrhosis, he added.

Dr. Younossi said the update offers a very clearly stated algorithm for how to identify patients whose condition is easily reversible with volume repletion, in comparison with those patients who require medical treatment or even liver transplantation.

“Those things are important because that pathway gives clinicians an idea of how to do this properly,” he said.

“The key for clinicians is to make sure they understand, in the context of cirrhosis, some of the easy things that they can do to prevent AKI,” he continued. He added that the use of NSAIDs in these patients is “going to be problematic.”

Dr. Kamath has a relationship with Sequana Medical. Other authors’ relevant financial relationships are listed in the original article. Dr. Reau has relationships with Salix and Intercept. Dr. Younossi has disclosed no relevant financial relationships.

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

This article was updated 12/12/2022.

Acute kidney injury (AKI) in patients with cirrhosis is potentially preventable, and there are clear steps that can be taken to manage and reverse the condition, concludes a clinical practice update from the American Gastroenterological Association.

AKI occurs in 47% of patients hospitalized with complications of cirrhosis and in approximately 30% of outpatients with cirrhosis, resulting in a total cost in the United States of $4 billion, explained Patrick S. Kamath, MD, division of gastroenterology and hepatology, Mayo Medical School, Rochester, Minn., one of the authors of this update.

Moreover, Dr. Kamath told this news organization, among patients with cirrhosis and AKI, morbidity and mortality is sevenfold higher in comparison to those without cirrhosis, and repeated episodes of AKI increase the risk of progression to chronic kidney disease.

To provide practical advice for the clinical management of patients with cirrhosis and AKI, the authors conducted an expert review of the best available published evidence and gathered expert opinion.

The update was published online in Clinical Gastroenterology and Hepatology.
 

Some key takeaways

Among its 14 best practice statements, it describes three situations indicative of AKI:

• A serum creatinine increase of 0.3 mg/dL or more within 48 hours, or
• A serum creatinine increase of 50% or more from baseline, which is a stable serum creatinine in the past 3 months.
• Reduction in urine output of up to 0.5 mL/kg per hour for more than 6 hours.

The update also emphasizes the importance of an accurate diagnosis, inasmuch as not all cases of AKI are due to hepatorenal syndrome (HRS), for example. It goes on to advise that the specific type of AKI be identified through medical history and physical examination, as well as with blood biochemistry, urine microscopic examination, urine chemistry, selected urinary biomarkers, and renal ultrasound.

Additionally, it underscores the need to identify and treat infections and to closely monitor fluid status.

Nancy S. Reau, MD, Rush Medical College, Chicago, who was not involved in the update, commented to this news organization that fluid status is important when giving albumin replacement therapy because of the increased risk for pulmonary edema.

She also highlighted that this update advises against transjugular intrahepatic portosystemic shunts (TIPSs) as a specific treatment for HRS-AKI, noting that, although the 2022 North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension do not advocate for TIPS for this indication, they also indicated that there was enough evidence to advise against it.

In other key best practice advice statements, the update advises clinicians to hold diuretics and nonselective beta blockers and to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs).
 

‘Timely’ update

Overall, Dr. Reau believes that the update is “timely, especially in light of the recent [U.S.] approval of terlipressin, which will change our treatment options.”

This update also supports the American Association for the Study of Liver Diseases (AASLD) 2021 Practice Guidance guidelines on HRS, she added.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., who was not involved in writing the update, told this news organization that the document is important because of the huge increase in mortality among patients with cirrhosis and AKI.

He commented that there has been much advancement in understanding the condition, with updated nomenclature and novel medical treatments, and that this makes the update timely.

Moreover, the update will help clinicians who are involved in the care of patients with cirrhosis, he added.

Dr. Younossi said the update offers a very clearly stated algorithm for how to identify patients whose condition is easily reversible with volume repletion, in comparison with those patients who require medical treatment or even liver transplantation.

“Those things are important because that pathway gives clinicians an idea of how to do this properly,” he said.

“The key for clinicians is to make sure they understand, in the context of cirrhosis, some of the easy things that they can do to prevent AKI,” he continued. He added that the use of NSAIDs in these patients is “going to be problematic.”

Dr. Kamath has a relationship with Sequana Medical. Other authors’ relevant financial relationships are listed in the original article. Dr. Reau has relationships with Salix and Intercept. Dr. Younossi has disclosed no relevant financial relationships.

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

This article was updated 12/12/2022.

Acute kidney injury (AKI) in patients with cirrhosis is potentially preventable, and there are clear steps that can be taken to manage and reverse the condition, concludes a clinical practice update from the American Gastroenterological Association.

AKI occurs in 47% of patients hospitalized with complications of cirrhosis and in approximately 30% of outpatients with cirrhosis, resulting in a total cost in the United States of $4 billion, explained Patrick S. Kamath, MD, division of gastroenterology and hepatology, Mayo Medical School, Rochester, Minn., one of the authors of this update.

Moreover, Dr. Kamath told this news organization, among patients with cirrhosis and AKI, morbidity and mortality is sevenfold higher in comparison to those without cirrhosis, and repeated episodes of AKI increase the risk of progression to chronic kidney disease.

To provide practical advice for the clinical management of patients with cirrhosis and AKI, the authors conducted an expert review of the best available published evidence and gathered expert opinion.

The update was published online in Clinical Gastroenterology and Hepatology.
 

Some key takeaways

Among its 14 best practice statements, it describes three situations indicative of AKI:

• A serum creatinine increase of 0.3 mg/dL or more within 48 hours, or
• A serum creatinine increase of 50% or more from baseline, which is a stable serum creatinine in the past 3 months.
• Reduction in urine output of up to 0.5 mL/kg per hour for more than 6 hours.

The update also emphasizes the importance of an accurate diagnosis, inasmuch as not all cases of AKI are due to hepatorenal syndrome (HRS), for example. It goes on to advise that the specific type of AKI be identified through medical history and physical examination, as well as with blood biochemistry, urine microscopic examination, urine chemistry, selected urinary biomarkers, and renal ultrasound.

Additionally, it underscores the need to identify and treat infections and to closely monitor fluid status.

Nancy S. Reau, MD, Rush Medical College, Chicago, who was not involved in the update, commented to this news organization that fluid status is important when giving albumin replacement therapy because of the increased risk for pulmonary edema.

She also highlighted that this update advises against transjugular intrahepatic portosystemic shunts (TIPSs) as a specific treatment for HRS-AKI, noting that, although the 2022 North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension do not advocate for TIPS for this indication, they also indicated that there was enough evidence to advise against it.

In other key best practice advice statements, the update advises clinicians to hold diuretics and nonselective beta blockers and to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs).
 

‘Timely’ update

Overall, Dr. Reau believes that the update is “timely, especially in light of the recent [U.S.] approval of terlipressin, which will change our treatment options.”

This update also supports the American Association for the Study of Liver Diseases (AASLD) 2021 Practice Guidance guidelines on HRS, she added.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., who was not involved in writing the update, told this news organization that the document is important because of the huge increase in mortality among patients with cirrhosis and AKI.

He commented that there has been much advancement in understanding the condition, with updated nomenclature and novel medical treatments, and that this makes the update timely.

Moreover, the update will help clinicians who are involved in the care of patients with cirrhosis, he added.

Dr. Younossi said the update offers a very clearly stated algorithm for how to identify patients whose condition is easily reversible with volume repletion, in comparison with those patients who require medical treatment or even liver transplantation.

“Those things are important because that pathway gives clinicians an idea of how to do this properly,” he said.

“The key for clinicians is to make sure they understand, in the context of cirrhosis, some of the easy things that they can do to prevent AKI,” he continued. He added that the use of NSAIDs in these patients is “going to be problematic.”

Dr. Kamath has a relationship with Sequana Medical. Other authors’ relevant financial relationships are listed in the original article. Dr. Reau has relationships with Salix and Intercept. Dr. Younossi has disclosed no relevant financial relationships.

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

This article was updated 12/12/2022.

The Food and Drug Administration has approved terlipressin (Terlivaz), the first and only drug approved for patients with hepatorenal syndrome (HRS).

HRS is characterized by progressive deterioration in kidney function in people with advanced liver disease.

Terlipressin is an injectable synthetic vasopressin analogue indicated for patients with HRS who are experiencing rapid deterioration of kidney function (type 1 HRS). The condition affects an estimated 35,000 Americans annually.

The safety and efficacy of terlipressin for type 1 HRS was assessed in the phase 3 CONFIRM trial, which involved 300 patients in the United States and Canada.

Patients received an injection of terlipressin (0.85 mg) or placebo every 6 hours for a maximum of 14 days. The dose was adjusted on the basis of changes in kidney function.

Twenty-nine percent of patients in the terlipressin group experienced improvement in kidney function, vs. 16% in the placebo group.

The CONFIRM trial met its primary endpoint of verified HRS reversal, defined as renal function improvement, avoidance of dialysis, and short-term survival (P = .012).

To achieve this endpoint, patients had to have two consecutive serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 2 hours apart by day 14 or be discharged from the hospital.

The most commonly observed adverse reactions that occurred in at least 4% of patients treated with terlipressin were abdominal pain (19.5%), nausea (16%), respiratory failure (15.5%), diarrhea (13%), and dyspnea (12.5%).

Results of the CONFIRM trial were published in The New England Journal of Medicine.

“Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it,” said Steven Romano, MD, executive vice president and chief scientific officer at Mallinckrodt, which makes the drug.

“Terlivaz gives physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis,” Dr. Romano said.

The company plans to launch the product in the coming weeks.

The application for terlipressin for HRS was granted priority review and fast-track status, as well as orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

The Food and Drug Administration has approved terlipressin (Terlivaz), the first and only drug approved for patients with hepatorenal syndrome (HRS).

HRS is characterized by progressive deterioration in kidney function in people with advanced liver disease.

Terlipressin is an injectable synthetic vasopressin analogue indicated for patients with HRS who are experiencing rapid deterioration of kidney function (type 1 HRS). The condition affects an estimated 35,000 Americans annually.

The safety and efficacy of terlipressin for type 1 HRS was assessed in the phase 3 CONFIRM trial, which involved 300 patients in the United States and Canada.

Patients received an injection of terlipressin (0.85 mg) or placebo every 6 hours for a maximum of 14 days. The dose was adjusted on the basis of changes in kidney function.

Twenty-nine percent of patients in the terlipressin group experienced improvement in kidney function, vs. 16% in the placebo group.

The CONFIRM trial met its primary endpoint of verified HRS reversal, defined as renal function improvement, avoidance of dialysis, and short-term survival (P = .012).

To achieve this endpoint, patients had to have two consecutive serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 2 hours apart by day 14 or be discharged from the hospital.

The most commonly observed adverse reactions that occurred in at least 4% of patients treated with terlipressin were abdominal pain (19.5%), nausea (16%), respiratory failure (15.5%), diarrhea (13%), and dyspnea (12.5%).

Results of the CONFIRM trial were published in The New England Journal of Medicine.

“Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it,” said Steven Romano, MD, executive vice president and chief scientific officer at Mallinckrodt, which makes the drug.

“Terlivaz gives physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis,” Dr. Romano said.

The company plans to launch the product in the coming weeks.

The application for terlipressin for HRS was granted priority review and fast-track status, as well as orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

The Food and Drug Administration has approved terlipressin (Terlivaz), the first and only drug approved for patients with hepatorenal syndrome (HRS).

HRS is characterized by progressive deterioration in kidney function in people with advanced liver disease.

Terlipressin is an injectable synthetic vasopressin analogue indicated for patients with HRS who are experiencing rapid deterioration of kidney function (type 1 HRS). The condition affects an estimated 35,000 Americans annually.

The safety and efficacy of terlipressin for type 1 HRS was assessed in the phase 3 CONFIRM trial, which involved 300 patients in the United States and Canada.

Patients received an injection of terlipressin (0.85 mg) or placebo every 6 hours for a maximum of 14 days. The dose was adjusted on the basis of changes in kidney function.

Twenty-nine percent of patients in the terlipressin group experienced improvement in kidney function, vs. 16% in the placebo group.

The CONFIRM trial met its primary endpoint of verified HRS reversal, defined as renal function improvement, avoidance of dialysis, and short-term survival (P = .012).

To achieve this endpoint, patients had to have two consecutive serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 2 hours apart by day 14 or be discharged from the hospital.

The most commonly observed adverse reactions that occurred in at least 4% of patients treated with terlipressin were abdominal pain (19.5%), nausea (16%), respiratory failure (15.5%), diarrhea (13%), and dyspnea (12.5%).

Results of the CONFIRM trial were published in The New England Journal of Medicine.

“Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it,” said Steven Romano, MD, executive vice president and chief scientific officer at Mallinckrodt, which makes the drug.

“Terlivaz gives physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis,” Dr. Romano said.

The company plans to launch the product in the coming weeks.

The application for terlipressin for HRS was granted priority review and fast-track status, as well as orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

New liver stiffness (LS) thresholds offer accurate prediction of disease progression and clinical outcomes in patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, according to investigators.

These new LS thresholds are more reliable because they are based on high-quality prospective data drawn from four randomized controlled trials, reported lead author Rohit Loomba, MD, of the University of California, San Diego, and colleagues.

“Retrospective studies report that increasing baseline LS by VCTE [vibration-controlled transient elastography] is associated with the risk of disease progression in patients with NAFLD [non-alcoholic fatty liver disease], but prospective data in well-characterized NASH cohorts with biopsy-confirmed advanced fibrosis are limited,” the investigators wrote in Gut. “The optimal LS thresholds for prognostication of fibrosis progression and decompensation are unknown.”

Seeking clarity, Dr. Loomba and colleagues leveraged data from two phase 3 placebo-controlled trials for selonsertib and two phase 2b placebo-controlled trials for simtuzumab.

“While the studies were discontinued prematurely due to lack of efficacy, the prospectively collected data in these well-characterized participants with serial liver biopsies provides a unique opportunity to study the association between baseline LS by VCTE and disease progression,” the investigators wrote.

Across all four studies, bridging fibrosis (F3) was present in 664 participants, while 734 individuals had cirrhosis (F4). In the selonsertib studies, fibrosis was staged at baseline and week 48. The simtuzumab studies measured liver fibrosis at baseline and week 96. Out of the 664 participants with bridging fibrosis, 103 (16%) progressed to cirrhosis. Among the 734 patients with cirrhosis, 27 (4%) experienced liver-related events. Comparing these outcomes with LS data at baseline and throughout the study revealed optimal LS thresholds.

The best threshold for predicting progression from bridging fibrosis to cirrhosis was 16.6 kPa. According to the authors, the sensitivity, specificity, positive predictive value, and negative predictive value of this threshold for progression to cirrhosis were 58%, 76%, 31%, and 91%, respectively. Among patients at or above 16.6 kPa, 31% progressed to cirrhosis, compared with 9.1% of those under that threshold. Furthermore, individuals with a baseline LS at or above 16.6 kPa had nearly four times greater risk of developing cirrhosis (adjusted hazard ratio, 3.99; 95% CI, 2.66­-5.98; P < .0001).

For patients with cirrhosis at baseline, the optimal threshold for predicting liver-related events, such as ascites, hepatic encephalopathy, and portal hypertension–related GI bleeding, liver transplantation, or mortality, was 30.7 kPa. The sensitivity, specificity, PPV, and NPV of this threshold for liver-related events were 62%, 87%, 10%, and 99%, respectively, according to the authors. Patients with an LS above this mark were 10 times as likely to experience liver-related events (aHR, 10.13; 95% CI, 4.38-23.41; P < .0001).

Scott L. Friedman, MD, chief of the division of liver diseases and dean for Therapeutic Discovery at the Icahn School of Medicine at Mount Sinai, New York, called the study “an important effort” that offers valuable insights for both researchers and practitioners.

“For clinical trials, [these thresholds] really allow for greater refinement or enrichment of patients who are suitable for enrollment in the trial because they’re at a higher risk of clinical problems that might be mitigated if the drug is effective,” Dr. Friedman said in an interview. “For clinical practice, it might indicate that the patient should either be fast tracked for a clinical trial or, more importantly, maybe needs to be referred for evaluation for a liver transplant. It may also indicate – although they didn’t look at it in this study – that there’s a need to begin or accelerate screening for liver cancer, which becomes an encroaching risk as the fibrosis advances to later stages.”

The study was funded by Gilead Sciences. The investigators disclosed additional relationships with Amgen, Eli Lilly, CohBar, and others. Dr. Friedman reported no relevant conflicts of interest.

New liver stiffness (LS) thresholds offer accurate prediction of disease progression and clinical outcomes in patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, according to investigators.

These new LS thresholds are more reliable because they are based on high-quality prospective data drawn from four randomized controlled trials, reported lead author Rohit Loomba, MD, of the University of California, San Diego, and colleagues.

“Retrospective studies report that increasing baseline LS by VCTE [vibration-controlled transient elastography] is associated with the risk of disease progression in patients with NAFLD [non-alcoholic fatty liver disease], but prospective data in well-characterized NASH cohorts with biopsy-confirmed advanced fibrosis are limited,” the investigators wrote in Gut. “The optimal LS thresholds for prognostication of fibrosis progression and decompensation are unknown.”

Seeking clarity, Dr. Loomba and colleagues leveraged data from two phase 3 placebo-controlled trials for selonsertib and two phase 2b placebo-controlled trials for simtuzumab.

“While the studies were discontinued prematurely due to lack of efficacy, the prospectively collected data in these well-characterized participants with serial liver biopsies provides a unique opportunity to study the association between baseline LS by VCTE and disease progression,” the investigators wrote.

Across all four studies, bridging fibrosis (F3) was present in 664 participants, while 734 individuals had cirrhosis (F4). In the selonsertib studies, fibrosis was staged at baseline and week 48. The simtuzumab studies measured liver fibrosis at baseline and week 96. Out of the 664 participants with bridging fibrosis, 103 (16%) progressed to cirrhosis. Among the 734 patients with cirrhosis, 27 (4%) experienced liver-related events. Comparing these outcomes with LS data at baseline and throughout the study revealed optimal LS thresholds.

The best threshold for predicting progression from bridging fibrosis to cirrhosis was 16.6 kPa. According to the authors, the sensitivity, specificity, positive predictive value, and negative predictive value of this threshold for progression to cirrhosis were 58%, 76%, 31%, and 91%, respectively. Among patients at or above 16.6 kPa, 31% progressed to cirrhosis, compared with 9.1% of those under that threshold. Furthermore, individuals with a baseline LS at or above 16.6 kPa had nearly four times greater risk of developing cirrhosis (adjusted hazard ratio, 3.99; 95% CI, 2.66­-5.98; P < .0001).

For patients with cirrhosis at baseline, the optimal threshold for predicting liver-related events, such as ascites, hepatic encephalopathy, and portal hypertension–related GI bleeding, liver transplantation, or mortality, was 30.7 kPa. The sensitivity, specificity, PPV, and NPV of this threshold for liver-related events were 62%, 87%, 10%, and 99%, respectively, according to the authors. Patients with an LS above this mark were 10 times as likely to experience liver-related events (aHR, 10.13; 95% CI, 4.38-23.41; P < .0001).

Scott L. Friedman, MD, chief of the division of liver diseases and dean for Therapeutic Discovery at the Icahn School of Medicine at Mount Sinai, New York, called the study “an important effort” that offers valuable insights for both researchers and practitioners.

“For clinical trials, [these thresholds] really allow for greater refinement or enrichment of patients who are suitable for enrollment in the trial because they’re at a higher risk of clinical problems that might be mitigated if the drug is effective,” Dr. Friedman said in an interview. “For clinical practice, it might indicate that the patient should either be fast tracked for a clinical trial or, more importantly, maybe needs to be referred for evaluation for a liver transplant. It may also indicate – although they didn’t look at it in this study – that there’s a need to begin or accelerate screening for liver cancer, which becomes an encroaching risk as the fibrosis advances to later stages.”

The study was funded by Gilead Sciences. The investigators disclosed additional relationships with Amgen, Eli Lilly, CohBar, and others. Dr. Friedman reported no relevant conflicts of interest.

New liver stiffness (LS) thresholds offer accurate prediction of disease progression and clinical outcomes in patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, according to investigators.

These new LS thresholds are more reliable because they are based on high-quality prospective data drawn from four randomized controlled trials, reported lead author Rohit Loomba, MD, of the University of California, San Diego, and colleagues.

“Retrospective studies report that increasing baseline LS by VCTE [vibration-controlled transient elastography] is associated with the risk of disease progression in patients with NAFLD [non-alcoholic fatty liver disease], but prospective data in well-characterized NASH cohorts with biopsy-confirmed advanced fibrosis are limited,” the investigators wrote in Gut. “The optimal LS thresholds for prognostication of fibrosis progression and decompensation are unknown.”

Seeking clarity, Dr. Loomba and colleagues leveraged data from two phase 3 placebo-controlled trials for selonsertib and two phase 2b placebo-controlled trials for simtuzumab.

“While the studies were discontinued prematurely due to lack of efficacy, the prospectively collected data in these well-characterized participants with serial liver biopsies provides a unique opportunity to study the association between baseline LS by VCTE and disease progression,” the investigators wrote.

Across all four studies, bridging fibrosis (F3) was present in 664 participants, while 734 individuals had cirrhosis (F4). In the selonsertib studies, fibrosis was staged at baseline and week 48. The simtuzumab studies measured liver fibrosis at baseline and week 96. Out of the 664 participants with bridging fibrosis, 103 (16%) progressed to cirrhosis. Among the 734 patients with cirrhosis, 27 (4%) experienced liver-related events. Comparing these outcomes with LS data at baseline and throughout the study revealed optimal LS thresholds.

The best threshold for predicting progression from bridging fibrosis to cirrhosis was 16.6 kPa. According to the authors, the sensitivity, specificity, positive predictive value, and negative predictive value of this threshold for progression to cirrhosis were 58%, 76%, 31%, and 91%, respectively. Among patients at or above 16.6 kPa, 31% progressed to cirrhosis, compared with 9.1% of those under that threshold. Furthermore, individuals with a baseline LS at or above 16.6 kPa had nearly four times greater risk of developing cirrhosis (adjusted hazard ratio, 3.99; 95% CI, 2.66­-5.98; P < .0001).

For patients with cirrhosis at baseline, the optimal threshold for predicting liver-related events, such as ascites, hepatic encephalopathy, and portal hypertension–related GI bleeding, liver transplantation, or mortality, was 30.7 kPa. The sensitivity, specificity, PPV, and NPV of this threshold for liver-related events were 62%, 87%, 10%, and 99%, respectively, according to the authors. Patients with an LS above this mark were 10 times as likely to experience liver-related events (aHR, 10.13; 95% CI, 4.38-23.41; P < .0001).

Scott L. Friedman, MD, chief of the division of liver diseases and dean for Therapeutic Discovery at the Icahn School of Medicine at Mount Sinai, New York, called the study “an important effort” that offers valuable insights for both researchers and practitioners.

“For clinical trials, [these thresholds] really allow for greater refinement or enrichment of patients who are suitable for enrollment in the trial because they’re at a higher risk of clinical problems that might be mitigated if the drug is effective,” Dr. Friedman said in an interview. “For clinical practice, it might indicate that the patient should either be fast tracked for a clinical trial or, more importantly, maybe needs to be referred for evaluation for a liver transplant. It may also indicate – although they didn’t look at it in this study – that there’s a need to begin or accelerate screening for liver cancer, which becomes an encroaching risk as the fibrosis advances to later stages.”

The study was funded by Gilead Sciences. The investigators disclosed additional relationships with Amgen, Eli Lilly, CohBar, and others. Dr. Friedman reported no relevant conflicts of interest.

Moving recycling bins and providing education to staff led to a reduction in the carbon footprint at a Portuguese hospital’s endoscopy unit, according to a study published in Gut.

“Sustainable endoscopy regarding waste handling was achievable and sustained over time, did not compromise productivity, and may be cost-effective for stakeholders,” wrote João A Cunha Neves, MD, MMSc, of Algarve University Hospital Centre in Portimão, Portugal, and his colleagues.

Stephen Barnes/iStock/Getty Images

Although other work has shown that several of the strategies for reducing endoscopic waste are ‘easy wins,’ the authors noted that “lack of awareness by most endoscopy staff regarding the expenses and correct categorisation of endoscopic waste is the primary barrier to recycling in many endoscopy units.”

The four-stage prospective study took place at the Portimão endoscopy unit of Algarve University Hospital Centre in Portugal. It began with a 4-week audit that involved weighing regulated medical waste (“material fully contaminated with blood or body fluids or containing infectious agents”) and landfill waste (nonrecyclable material that isn’t fully contaminated). The researchers excluded from the analysis all waste from sharps containers, pre- and postprocedure activities, and endoscope reprocessing.

The second stage was one week of medical, nursing, and auxiliary team education about handling waste, in part based on observations collected during the first stage. Each endoscopy generates an estimated 1.5 kg of plastic waste, but recycling bins often are not available for the 0.3 kg of waste that’s recyclable. During the second stage, recycling bins were placed in endoscopy rooms while regulated medical waste and landfill bins were moved elsewhere.

The final two stages involved weighing both types of waste 1 month after the training and then 4 months after the training. For their calculations, the researchers assumed that 1 kg of landfill waste equated to 1 kg of carbon dioxide and 1 kg of regulated medical waste equated to 3 kg of carbon dioxide.

At the third stage, mean total waste fell by 12.9%, albeit not statistically significantly (P = .16), while the 41.4% regulated medical waste reduction was significant (P = .01). Landfill waste had increased 12.3% and both paper (0 to 1.2 kg) and plastic (0 to 2.1 kg) recycling waste increased. Mean endoscopy load had not significantly changed (46.2 vs. 44.5). Overall carbon dioxide was reduced by 31.6%, from 109.7 kg of carbon dioxide to 74.9 kg (P = .018), equating to an annual decrease of 1,665.6 kg. At four months postintervention, these effects remained.

“In both assessment periods, total waste produced by diagnostic standard endoscopic procedures was similar, but both regulated medical waste and overall carbon footprint were reduced,” the authors reported.

In a four-question assessment of the intervention with staff, “the entire team agreed that the study did not interfere with the daily work routine and was helpful in raising awareness about waste sorting within the unit,” the authors reported. The staff “also acknowledged that recycling waste allowed for more sustainable activity within the endoscopy unit, and that the achievements of the study were to be maintained in the future.”
 

How feasible is change?

The authors noted that health care accounts for 4.4% of the world’s carbon footprint and that endoscopy is the third largest generator of hospital medical waste, primarily because of single-use consumables. However, 71% of that health care carbon footprint comes from supply chain issues, particularly transportation, John I. Allen, MD, MBA, a retired clinical professor of medicine at the University Michigan, Ann Arbor, said in an interview. “Facility emissions add 17% and heating/cooling add 12%,” he said. “So, the actual footprint of endoscopy is quite small.”

Reducing single-use equipment and disposables by a third is a small overall impact considering the “labor-intensive education and monitoring system,” said Dr. Allen, who was not involved in the study. “That said, this paper and numerous others remind us of small steps that we can take – mostly to raise awareness about new technologies and more sustainable processes that are available or should be studied – to help transition us from the current [terrible] state to a more climate-friendly style of practice and life.”

One of the study’s limitations was the lack of a cost-benefit or impact analysis, according to Dr. Allen. Climate policies claiming to have local impact can be problematic when they “ignore both externalities and the actual wider impact on gas or temperature mitigation,” he added.

But he noted that “many health care systems are already implementing new ways of working with temperature- and carbon-mitigation in mind,” such as his own institution’s pledge to become carbon-neutral within a year. One step on that path has included transitioning more than 30% of their clinic visits to virtual visits, “thus saving [literally] millions of miles in travel and altering our parking construction plans,” Dr. Allen said.

“Reduction in climate impact will come from new ways to manufacture endoscopes, less reliance on single-use equipment, and increasing use of materials that encourage recycling,” Dr. Allen said. “In order to achieve meaningful climate impact, we need research into what current regulations and processes are necessary to protect patients and staff from infection transmission while creating an environmentally favorable workflow.”
 

Where does making a difference begin?

Another limitation was simply the small size of the department itself, which limits how much impact the intervention can have, but the study also showed the feasibility of getting buy-in from a department to make meaningful changes, according to Bishr Omary, MD, PhD, professor of medicine at Rutgers University’s Robert Wood Johnson Medical School, Piscataway, N.J. He was not involved in the study.

“Culture is an important aspect of this, but that’s where education comes in,” Dr. Omary said in an interview. “Leadership has to try to encourage and incentivize different units, not just endoscopy, but other surgery, too. I think the most effective approach is going to be top-down, where hospitals and health systems buy into this.”

One challenge to that buy-in is that climate change has become political, said Linda Anh B. Nguyen, MD, clinical professor of medicine and vice chief of clinical operations in Stanford (Calif.) University’s division of gastroenterology and hepatology.

“There may be resistance to implementation by those who do not see the value of reducing waste,” Dr. Nguyen, who was not involved in this study, said in an interview. “Successful implementation requires a culture change and reducing the physical barriers to make waste reduction easier. Having an advocate for the program embedded within the endoscopy unit will help with implementation.”

One of the advantages of the intervention in this study, Dr. Nguyen said, was its relative ease of implementation.

“The next step would be identifying which of the items that go into landfill can be replaced with reusable products,” Dr. Nguyen added.

Dr. Omary pointed to Practice Greenhealth as an example of an organization working toward the goal of climate change mitigation through a wide range of initiatives, including ones he has written about. The responsibility for reducing carbon footprints should be shared among individuals, institutions, and systems, Dr. Omary said, adding that individuals’ travel, such as to medical meetings, is a major contributor to greenhouse gas emissions.

A forthcoming publication from the four major gastroenterology medical organizations will outline additional ways gastroenterology can address climate change mitigation, Dr. Omary noted.

Dr. Nguyen said that gastroenterologists, as well as the entire health care industry, have a responsibility to combat climate change through waste reduction and that it can be done without sacrificing individual patient safety.

“Climate change must be at the forefront of our priorities for present and future generations,” Dr. Nguyen said. “We need to leave this world better than when we entered.”

But much of that change must especially occur at levels far higher than individual physicians or institutions, Dr. Allen said.

“Major responsibility for altering gastroenterology practices in order to mitigate climate change must originate in regulatory agencies and the manufacturers of our equipment,” Dr. Allen said. “Regulations must be based on demonstrated positive impact that is cost-effective for practices and health care systems.”

The research did not use external funding, and the authors reported no financial disclosures or conflicts of interests. Dr. Allen has consulted for Topography Health, OSHI Health, and Lynxmd. Dr. Nguyen has consulted for Alnylam, Ardelyx, Eli Lilly, Evoke Pharma, Ironwood, Pendulum, Phathom, Neurogastx, Sanofi, and Takeda; has served on the advisory board of Gemelli Biotech; and has received grants from Bold Health and Vanda. Dr. Omary had no disclosures.

Moving recycling bins and providing education to staff led to a reduction in the carbon footprint at a Portuguese hospital’s endoscopy unit, according to a study published in Gut.

“Sustainable endoscopy regarding waste handling was achievable and sustained over time, did not compromise productivity, and may be cost-effective for stakeholders,” wrote João A Cunha Neves, MD, MMSc, of Algarve University Hospital Centre in Portimão, Portugal, and his colleagues.

Stephen Barnes/iStock/Getty Images

Although other work has shown that several of the strategies for reducing endoscopic waste are ‘easy wins,’ the authors noted that “lack of awareness by most endoscopy staff regarding the expenses and correct categorisation of endoscopic waste is the primary barrier to recycling in many endoscopy units.”

The four-stage prospective study took place at the Portimão endoscopy unit of Algarve University Hospital Centre in Portugal. It began with a 4-week audit that involved weighing regulated medical waste (“material fully contaminated with blood or body fluids or containing infectious agents”) and landfill waste (nonrecyclable material that isn’t fully contaminated). The researchers excluded from the analysis all waste from sharps containers, pre- and postprocedure activities, and endoscope reprocessing.

The second stage was one week of medical, nursing, and auxiliary team education about handling waste, in part based on observations collected during the first stage. Each endoscopy generates an estimated 1.5 kg of plastic waste, but recycling bins often are not available for the 0.3 kg of waste that’s recyclable. During the second stage, recycling bins were placed in endoscopy rooms while regulated medical waste and landfill bins were moved elsewhere.

The final two stages involved weighing both types of waste 1 month after the training and then 4 months after the training. For their calculations, the researchers assumed that 1 kg of landfill waste equated to 1 kg of carbon dioxide and 1 kg of regulated medical waste equated to 3 kg of carbon dioxide.

At the third stage, mean total waste fell by 12.9%, albeit not statistically significantly (P = .16), while the 41.4% regulated medical waste reduction was significant (P = .01). Landfill waste had increased 12.3% and both paper (0 to 1.2 kg) and plastic (0 to 2.1 kg) recycling waste increased. Mean endoscopy load had not significantly changed (46.2 vs. 44.5). Overall carbon dioxide was reduced by 31.6%, from 109.7 kg of carbon dioxide to 74.9 kg (P = .018), equating to an annual decrease of 1,665.6 kg. At four months postintervention, these effects remained.

“In both assessment periods, total waste produced by diagnostic standard endoscopic procedures was similar, but both regulated medical waste and overall carbon footprint were reduced,” the authors reported.

In a four-question assessment of the intervention with staff, “the entire team agreed that the study did not interfere with the daily work routine and was helpful in raising awareness about waste sorting within the unit,” the authors reported. The staff “also acknowledged that recycling waste allowed for more sustainable activity within the endoscopy unit, and that the achievements of the study were to be maintained in the future.”
 

How feasible is change?

The authors noted that health care accounts for 4.4% of the world’s carbon footprint and that endoscopy is the third largest generator of hospital medical waste, primarily because of single-use consumables. However, 71% of that health care carbon footprint comes from supply chain issues, particularly transportation, John I. Allen, MD, MBA, a retired clinical professor of medicine at the University Michigan, Ann Arbor, said in an interview. “Facility emissions add 17% and heating/cooling add 12%,” he said. “So, the actual footprint of endoscopy is quite small.”

Reducing single-use equipment and disposables by a third is a small overall impact considering the “labor-intensive education and monitoring system,” said Dr. Allen, who was not involved in the study. “That said, this paper and numerous others remind us of small steps that we can take – mostly to raise awareness about new technologies and more sustainable processes that are available or should be studied – to help transition us from the current [terrible] state to a more climate-friendly style of practice and life.”

One of the study’s limitations was the lack of a cost-benefit or impact analysis, according to Dr. Allen. Climate policies claiming to have local impact can be problematic when they “ignore both externalities and the actual wider impact on gas or temperature mitigation,” he added.

But he noted that “many health care systems are already implementing new ways of working with temperature- and carbon-mitigation in mind,” such as his own institution’s pledge to become carbon-neutral within a year. One step on that path has included transitioning more than 30% of their clinic visits to virtual visits, “thus saving [literally] millions of miles in travel and altering our parking construction plans,” Dr. Allen said.

“Reduction in climate impact will come from new ways to manufacture endoscopes, less reliance on single-use equipment, and increasing use of materials that encourage recycling,” Dr. Allen said. “In order to achieve meaningful climate impact, we need research into what current regulations and processes are necessary to protect patients and staff from infection transmission while creating an environmentally favorable workflow.”
 

Where does making a difference begin?

Another limitation was simply the small size of the department itself, which limits how much impact the intervention can have, but the study also showed the feasibility of getting buy-in from a department to make meaningful changes, according to Bishr Omary, MD, PhD, professor of medicine at Rutgers University’s Robert Wood Johnson Medical School, Piscataway, N.J. He was not involved in the study.

“Culture is an important aspect of this, but that’s where education comes in,” Dr. Omary said in an interview. “Leadership has to try to encourage and incentivize different units, not just endoscopy, but other surgery, too. I think the most effective approach is going to be top-down, where hospitals and health systems buy into this.”

One challenge to that buy-in is that climate change has become political, said Linda Anh B. Nguyen, MD, clinical professor of medicine and vice chief of clinical operations in Stanford (Calif.) University’s division of gastroenterology and hepatology.

“There may be resistance to implementation by those who do not see the value of reducing waste,” Dr. Nguyen, who was not involved in this study, said in an interview. “Successful implementation requires a culture change and reducing the physical barriers to make waste reduction easier. Having an advocate for the program embedded within the endoscopy unit will help with implementation.”

One of the advantages of the intervention in this study, Dr. Nguyen said, was its relative ease of implementation.

“The next step would be identifying which of the items that go into landfill can be replaced with reusable products,” Dr. Nguyen added.

Dr. Omary pointed to Practice Greenhealth as an example of an organization working toward the goal of climate change mitigation through a wide range of initiatives, including ones he has written about. The responsibility for reducing carbon footprints should be shared among individuals, institutions, and systems, Dr. Omary said, adding that individuals’ travel, such as to medical meetings, is a major contributor to greenhouse gas emissions.

A forthcoming publication from the four major gastroenterology medical organizations will outline additional ways gastroenterology can address climate change mitigation, Dr. Omary noted.

Dr. Nguyen said that gastroenterologists, as well as the entire health care industry, have a responsibility to combat climate change through waste reduction and that it can be done without sacrificing individual patient safety.

“Climate change must be at the forefront of our priorities for present and future generations,” Dr. Nguyen said. “We need to leave this world better than when we entered.”

But much of that change must especially occur at levels far higher than individual physicians or institutions, Dr. Allen said.

“Major responsibility for altering gastroenterology practices in order to mitigate climate change must originate in regulatory agencies and the manufacturers of our equipment,” Dr. Allen said. “Regulations must be based on demonstrated positive impact that is cost-effective for practices and health care systems.”

The research did not use external funding, and the authors reported no financial disclosures or conflicts of interests. Dr. Allen has consulted for Topography Health, OSHI Health, and Lynxmd. Dr. Nguyen has consulted for Alnylam, Ardelyx, Eli Lilly, Evoke Pharma, Ironwood, Pendulum, Phathom, Neurogastx, Sanofi, and Takeda; has served on the advisory board of Gemelli Biotech; and has received grants from Bold Health and Vanda. Dr. Omary had no disclosures.

Moving recycling bins and providing education to staff led to a reduction in the carbon footprint at a Portuguese hospital’s endoscopy unit, according to a study published in Gut.

“Sustainable endoscopy regarding waste handling was achievable and sustained over time, did not compromise productivity, and may be cost-effective for stakeholders,” wrote João A Cunha Neves, MD, MMSc, of Algarve University Hospital Centre in Portimão, Portugal, and his colleagues.

Stephen Barnes/iStock/Getty Images

Although other work has shown that several of the strategies for reducing endoscopic waste are ‘easy wins,’ the authors noted that “lack of awareness by most endoscopy staff regarding the expenses and correct categorisation of endoscopic waste is the primary barrier to recycling in many endoscopy units.”

The four-stage prospective study took place at the Portimão endoscopy unit of Algarve University Hospital Centre in Portugal. It began with a 4-week audit that involved weighing regulated medical waste (“material fully contaminated with blood or body fluids or containing infectious agents”) and landfill waste (nonrecyclable material that isn’t fully contaminated). The researchers excluded from the analysis all waste from sharps containers, pre- and postprocedure activities, and endoscope reprocessing.

The second stage was one week of medical, nursing, and auxiliary team education about handling waste, in part based on observations collected during the first stage. Each endoscopy generates an estimated 1.5 kg of plastic waste, but recycling bins often are not available for the 0.3 kg of waste that’s recyclable. During the second stage, recycling bins were placed in endoscopy rooms while regulated medical waste and landfill bins were moved elsewhere.

The final two stages involved weighing both types of waste 1 month after the training and then 4 months after the training. For their calculations, the researchers assumed that 1 kg of landfill waste equated to 1 kg of carbon dioxide and 1 kg of regulated medical waste equated to 3 kg of carbon dioxide.

At the third stage, mean total waste fell by 12.9%, albeit not statistically significantly (P = .16), while the 41.4% regulated medical waste reduction was significant (P = .01). Landfill waste had increased 12.3% and both paper (0 to 1.2 kg) and plastic (0 to 2.1 kg) recycling waste increased. Mean endoscopy load had not significantly changed (46.2 vs. 44.5). Overall carbon dioxide was reduced by 31.6%, from 109.7 kg of carbon dioxide to 74.9 kg (P = .018), equating to an annual decrease of 1,665.6 kg. At four months postintervention, these effects remained.

“In both assessment periods, total waste produced by diagnostic standard endoscopic procedures was similar, but both regulated medical waste and overall carbon footprint were reduced,” the authors reported.

In a four-question assessment of the intervention with staff, “the entire team agreed that the study did not interfere with the daily work routine and was helpful in raising awareness about waste sorting within the unit,” the authors reported. The staff “also acknowledged that recycling waste allowed for more sustainable activity within the endoscopy unit, and that the achievements of the study were to be maintained in the future.”
 

How feasible is change?

The authors noted that health care accounts for 4.4% of the world’s carbon footprint and that endoscopy is the third largest generator of hospital medical waste, primarily because of single-use consumables. However, 71% of that health care carbon footprint comes from supply chain issues, particularly transportation, John I. Allen, MD, MBA, a retired clinical professor of medicine at the University Michigan, Ann Arbor, said in an interview. “Facility emissions add 17% and heating/cooling add 12%,” he said. “So, the actual footprint of endoscopy is quite small.”

Reducing single-use equipment and disposables by a third is a small overall impact considering the “labor-intensive education and monitoring system,” said Dr. Allen, who was not involved in the study. “That said, this paper and numerous others remind us of small steps that we can take – mostly to raise awareness about new technologies and more sustainable processes that are available or should be studied – to help transition us from the current [terrible] state to a more climate-friendly style of practice and life.”

One of the study’s limitations was the lack of a cost-benefit or impact analysis, according to Dr. Allen. Climate policies claiming to have local impact can be problematic when they “ignore both externalities and the actual wider impact on gas or temperature mitigation,” he added.

But he noted that “many health care systems are already implementing new ways of working with temperature- and carbon-mitigation in mind,” such as his own institution’s pledge to become carbon-neutral within a year. One step on that path has included transitioning more than 30% of their clinic visits to virtual visits, “thus saving [literally] millions of miles in travel and altering our parking construction plans,” Dr. Allen said.

“Reduction in climate impact will come from new ways to manufacture endoscopes, less reliance on single-use equipment, and increasing use of materials that encourage recycling,” Dr. Allen said. “In order to achieve meaningful climate impact, we need research into what current regulations and processes are necessary to protect patients and staff from infection transmission while creating an environmentally favorable workflow.”
 

Where does making a difference begin?

Another limitation was simply the small size of the department itself, which limits how much impact the intervention can have, but the study also showed the feasibility of getting buy-in from a department to make meaningful changes, according to Bishr Omary, MD, PhD, professor of medicine at Rutgers University’s Robert Wood Johnson Medical School, Piscataway, N.J. He was not involved in the study.

“Culture is an important aspect of this, but that’s where education comes in,” Dr. Omary said in an interview. “Leadership has to try to encourage and incentivize different units, not just endoscopy, but other surgery, too. I think the most effective approach is going to be top-down, where hospitals and health systems buy into this.”

One challenge to that buy-in is that climate change has become political, said Linda Anh B. Nguyen, MD, clinical professor of medicine and vice chief of clinical operations in Stanford (Calif.) University’s division of gastroenterology and hepatology.

“There may be resistance to implementation by those who do not see the value of reducing waste,” Dr. Nguyen, who was not involved in this study, said in an interview. “Successful implementation requires a culture change and reducing the physical barriers to make waste reduction easier. Having an advocate for the program embedded within the endoscopy unit will help with implementation.”

One of the advantages of the intervention in this study, Dr. Nguyen said, was its relative ease of implementation.

“The next step would be identifying which of the items that go into landfill can be replaced with reusable products,” Dr. Nguyen added.

Dr. Omary pointed to Practice Greenhealth as an example of an organization working toward the goal of climate change mitigation through a wide range of initiatives, including ones he has written about. The responsibility for reducing carbon footprints should be shared among individuals, institutions, and systems, Dr. Omary said, adding that individuals’ travel, such as to medical meetings, is a major contributor to greenhouse gas emissions.

A forthcoming publication from the four major gastroenterology medical organizations will outline additional ways gastroenterology can address climate change mitigation, Dr. Omary noted.

Dr. Nguyen said that gastroenterologists, as well as the entire health care industry, have a responsibility to combat climate change through waste reduction and that it can be done without sacrificing individual patient safety.

“Climate change must be at the forefront of our priorities for present and future generations,” Dr. Nguyen said. “We need to leave this world better than when we entered.”

But much of that change must especially occur at levels far higher than individual physicians or institutions, Dr. Allen said.

“Major responsibility for altering gastroenterology practices in order to mitigate climate change must originate in regulatory agencies and the manufacturers of our equipment,” Dr. Allen said. “Regulations must be based on demonstrated positive impact that is cost-effective for practices and health care systems.”

The research did not use external funding, and the authors reported no financial disclosures or conflicts of interests. Dr. Allen has consulted for Topography Health, OSHI Health, and Lynxmd. Dr. Nguyen has consulted for Alnylam, Ardelyx, Eli Lilly, Evoke Pharma, Ironwood, Pendulum, Phathom, Neurogastx, Sanofi, and Takeda; has served on the advisory board of Gemelli Biotech; and has received grants from Bold Health and Vanda. Dr. Omary had no disclosures.

There is a rich science around the management of the cirrhotic liver itself – for example, pragmatic prognostic markers such as MELDNa, data-driven strategies to prevent variceal bleeding, and well-utilized algorithms to manage ascites.

But what is new in cirrhosis management is an emerging science around the management of the person living with cirrhosis – a science that seeks to understand how these individuals function in their day-to-day lives, how they feel, and how they can best prepare for their future. What is so exciting is that the field is moving beyond simply understanding those complex aspects of the patient, which is important in and of itself, toward developing practical tools to help clinicians assess their patients’ symptoms and strategies to help improve their patients’ lived experience. Although terms such as “frailty,” “palliative care,” and “advance care planning” are not new in cirrhosis per se, they are now recognized as distinct patient-centered constructs that are highly relevant to the management of patients with cirrhosis. Furthermore, these constructs have been codified through two recent guidance statements sponsored by the American Association for the Study of Liver Diseases.^1,2 Pragmatic tools are emerging to facilitate the integration of these patient-centered constructs into routine clinical practice, tools such as the Liver Frailty Index, the Edmonton Symptom Assessment System adapted for patients with cirrhosis, and structured frameworks for guiding goals-of-care discussions. The incorporation of these tools allows for new management strategies directed toward improving the patient’s experience such as timely initiation of nutrition and activity-based interventions, algorithms for pharmacologic and nonpharmacologic strategies for symptom management, and online/video-guided approaches to articulating one’s goals of care.

So, what is new in cirrhosis management is that we are moving beyond managing the cirrhotic liver itself to considering how cirrhosis and its complications impact the patient as a whole. In doing so, we are turning the art of hepatology care into science that can be applied systematically at the bedside for every patient, with the goal of improving care for all patients living with cirrhosis.
 

Dr. Lai holds the Endowed Professorship of Liver Health and Transplantation at the University of California, San Francisco. She reports having no conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.

References

1. Lai JC et al. Hepatology. 2021 Sep;74(3):1611-44.

2. Rogal S et al. Hepatology. 2022 Feb 1. doi: 10.1002/hep.32378.

There is a rich science around the management of the cirrhotic liver itself – for example, pragmatic prognostic markers such as MELDNa, data-driven strategies to prevent variceal bleeding, and well-utilized algorithms to manage ascites.

But what is new in cirrhosis management is an emerging science around the management of the person living with cirrhosis – a science that seeks to understand how these individuals function in their day-to-day lives, how they feel, and how they can best prepare for their future. What is so exciting is that the field is moving beyond simply understanding those complex aspects of the patient, which is important in and of itself, toward developing practical tools to help clinicians assess their patients’ symptoms and strategies to help improve their patients’ lived experience. Although terms such as “frailty,” “palliative care,” and “advance care planning” are not new in cirrhosis per se, they are now recognized as distinct patient-centered constructs that are highly relevant to the management of patients with cirrhosis. Furthermore, these constructs have been codified through two recent guidance statements sponsored by the American Association for the Study of Liver Diseases.^1,2 Pragmatic tools are emerging to facilitate the integration of these patient-centered constructs into routine clinical practice, tools such as the Liver Frailty Index, the Edmonton Symptom Assessment System adapted for patients with cirrhosis, and structured frameworks for guiding goals-of-care discussions. The incorporation of these tools allows for new management strategies directed toward improving the patient’s experience such as timely initiation of nutrition and activity-based interventions, algorithms for pharmacologic and nonpharmacologic strategies for symptom management, and online/video-guided approaches to articulating one’s goals of care.

So, what is new in cirrhosis management is that we are moving beyond managing the cirrhotic liver itself to considering how cirrhosis and its complications impact the patient as a whole. In doing so, we are turning the art of hepatology care into science that can be applied systematically at the bedside for every patient, with the goal of improving care for all patients living with cirrhosis.
 

Dr. Lai holds the Endowed Professorship of Liver Health and Transplantation at the University of California, San Francisco. She reports having no conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.

References

1. Lai JC et al. Hepatology. 2021 Sep;74(3):1611-44.

2. Rogal S et al. Hepatology. 2022 Feb 1. doi: 10.1002/hep.32378.

There is a rich science around the management of the cirrhotic liver itself – for example, pragmatic prognostic markers such as MELDNa, data-driven strategies to prevent variceal bleeding, and well-utilized algorithms to manage ascites.

But what is new in cirrhosis management is an emerging science around the management of the person living with cirrhosis – a science that seeks to understand how these individuals function in their day-to-day lives, how they feel, and how they can best prepare for their future. What is so exciting is that the field is moving beyond simply understanding those complex aspects of the patient, which is important in and of itself, toward developing practical tools to help clinicians assess their patients’ symptoms and strategies to help improve their patients’ lived experience. Although terms such as “frailty,” “palliative care,” and “advance care planning” are not new in cirrhosis per se, they are now recognized as distinct patient-centered constructs that are highly relevant to the management of patients with cirrhosis. Furthermore, these constructs have been codified through two recent guidance statements sponsored by the American Association for the Study of Liver Diseases.^1,2 Pragmatic tools are emerging to facilitate the integration of these patient-centered constructs into routine clinical practice, tools such as the Liver Frailty Index, the Edmonton Symptom Assessment System adapted for patients with cirrhosis, and structured frameworks for guiding goals-of-care discussions. The incorporation of these tools allows for new management strategies directed toward improving the patient’s experience such as timely initiation of nutrition and activity-based interventions, algorithms for pharmacologic and nonpharmacologic strategies for symptom management, and online/video-guided approaches to articulating one’s goals of care.

So, what is new in cirrhosis management is that we are moving beyond managing the cirrhotic liver itself to considering how cirrhosis and its complications impact the patient as a whole. In doing so, we are turning the art of hepatology care into science that can be applied systematically at the bedside for every patient, with the goal of improving care for all patients living with cirrhosis.
 

Dr. Lai holds the Endowed Professorship of Liver Health and Transplantation at the University of California, San Francisco. She reports having no conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.

References

1. Lai JC et al. Hepatology. 2021 Sep;74(3):1611-44.

2. Rogal S et al. Hepatology. 2022 Feb 1. doi: 10.1002/hep.32378.

Living-donor liver transplant recipients gained an additional 13-17 years of life, compared with patients who remained on the wait list, according to a retrospective case-control study.

The data suggest that the life-years gained are comparable to or greater than those conferred by either other lifesaving procedures or liver transplant from a deceased donor, wrote the researchers, led by Whitney Jackson, MD, assistant professor of gastroenterology and medical director of living-donor liver transplantation at the University of Colorado Anschutz Medical Campus.

“Despite the acceptance of living-donor liver transplant as a lifesaving procedure for end-stage liver disease, it remains underused in the United States,” the authors wrote in JAMA Surgery. “This study’s findings challenge current perceptions regarding when the survival benefit of a living-donor transplant occurs.”

Dr. Jackson and colleagues conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database for 119,275 U.S. liver transplant candidates and recipients from January 2012 to September 2021. They assessed the survival benefit, life-years saved, and the Model for End-Stage Liver Disease incorporating sodium levels (MELD-Na) score at which the survival benefit was obtained, compared with those who remained on the wait list.

The research team included 116,455 liver transplant candidates who were 18 and older and assigned to the wait list, as well as 2,820 patients who received a living-donor liver transplant. Patients listed for retransplant or multiorgan transplant were excluded, as were those with prior kidney or liver transplants.

The mean age of the study participants was 55 years, and 63% were men. Overall, 70.2% were White, 15.8% were Hispanic or Latinx, 8.2% were Black or African American, 4.3% were Asian, 0.9% were American Indian or Alaska Native, and 0.2% were Native Hawaiian or Pacific Islander. The most common etiologies were alcoholic cirrhosis (23.8%) and nonalcoholic steatohepatitis (15.9%).

Compared with patients on the wait list, recipients of a living-donor liver transplant were younger, more often women, more educated, and more often White. A greater proportion of transplant recipients had a primary etiology of nonalcoholic steatohepatitis (19.8%) and cholestatic liver disease (24.1%). At wait list placement, one-third of candidates had a MELD-Na score of 14 or higher.

The research team found a significant survival benefit for patients receiving a living-donor liver transplant based on mortality risk and survival scores. The survival benefit was significant at a MELD-Na score as low as 11, with a 34% decrease(95% confidence interval [CI], 17.4%-52.0%) in mortality compared with the wait list. In addition, mortality risk models confirmed a survival benefit for patients with a MELD-Na score of 11 or higher at 1 year after transplant (adjusted hazard ratio, 0.64; 95% CI, 0.47-0.88; P = .006). At a MELD-Na score of 14-16, mortality decreased by about 50% (aHR, 0.47; 95% CI, 0.34-0.66; P < .001).

The probability of death from a living-donor liver transplant for patients with very low MELD-Na scores (between 6 and 10) was greater than that for patients on the wait list for the first 259 days, at which point the risk of death for both groups was equal. At 471 days, the probability of survival in both groups was equal. As the MELD-Na score increased, both the time to equal risk of death and the time to equal survival decreased, demonstrating that the survival benefit occurs much earlier for patients with a higher MELD-Na score.

Analysis of life-years from transplant showed living-donor transplant recipients gained 13-17 life-years compared to those who didn’t receive one.

“Living-donor liver transplantation is a valuable yet underutilized strategy to address the significant organ shortage and long waiting times on the transplant list in the U.S.,” said Renu Dhanasekaran, MD, PhD, assistant professor of gastroenterology and hepatology at Stanford (Calif.) University.

Dr. Dhanasekaran, who wasn’t involved with this study, also welcomed the finding that living-donor liver transplantation can benefit patients with low MELD-Na scores, even below the expected cutoff at 15. According to the study authors, previous research had suggested benefit would be seen only at MELD-Na 15 and above.

“In my practice, I have several patients whose symptoms are out of proportion to their MELD score, and data like this will convince them and their potential donors to avail a transplant at an earlier stage,” she said.

The findings challenge the current paradigm around the timing of referral for a liver transplant and may have ramifications for allocation policies for deceased donors, the study authors wrote. The data can also help to contextualize risk-benefit discussions for donors and recipients.

“Donating a part of one’s liver to save a patient suffering from end-stage liver disease is an incredible act of selfless love,” Dr. Dhanasekaran said. “I hope strong positive data from studies like this one encourage more donors, patients, and transplant centers to expand the use of [living-donor liver transplant].”

The authors reported no grant support or funding sources for this study. One author disclosed being married to the current chair of the United Network for Organ Sharing’s Liver and Intestinal Organ Transplantation Committee. No other conflicts of interest were reported. Dr. Dhanasekaran reported no relevant disclosures.

Living-donor liver transplant recipients gained an additional 13-17 years of life, compared with patients who remained on the wait list, according to a retrospective case-control study.

The data suggest that the life-years gained are comparable to or greater than those conferred by either other lifesaving procedures or liver transplant from a deceased donor, wrote the researchers, led by Whitney Jackson, MD, assistant professor of gastroenterology and medical director of living-donor liver transplantation at the University of Colorado Anschutz Medical Campus.

“Despite the acceptance of living-donor liver transplant as a lifesaving procedure for end-stage liver disease, it remains underused in the United States,” the authors wrote in JAMA Surgery. “This study’s findings challenge current perceptions regarding when the survival benefit of a living-donor transplant occurs.”

Dr. Jackson and colleagues conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database for 119,275 U.S. liver transplant candidates and recipients from January 2012 to September 2021. They assessed the survival benefit, life-years saved, and the Model for End-Stage Liver Disease incorporating sodium levels (MELD-Na) score at which the survival benefit was obtained, compared with those who remained on the wait list.

The research team included 116,455 liver transplant candidates who were 18 and older and assigned to the wait list, as well as 2,820 patients who received a living-donor liver transplant. Patients listed for retransplant or multiorgan transplant were excluded, as were those with prior kidney or liver transplants.

The mean age of the study participants was 55 years, and 63% were men. Overall, 70.2% were White, 15.8% were Hispanic or Latinx, 8.2% were Black or African American, 4.3% were Asian, 0.9% were American Indian or Alaska Native, and 0.2% were Native Hawaiian or Pacific Islander. The most common etiologies were alcoholic cirrhosis (23.8%) and nonalcoholic steatohepatitis (15.9%).

Compared with patients on the wait list, recipients of a living-donor liver transplant were younger, more often women, more educated, and more often White. A greater proportion of transplant recipients had a primary etiology of nonalcoholic steatohepatitis (19.8%) and cholestatic liver disease (24.1%). At wait list placement, one-third of candidates had a MELD-Na score of 14 or higher.

The research team found a significant survival benefit for patients receiving a living-donor liver transplant based on mortality risk and survival scores. The survival benefit was significant at a MELD-Na score as low as 11, with a 34% decrease(95% confidence interval [CI], 17.4%-52.0%) in mortality compared with the wait list. In addition, mortality risk models confirmed a survival benefit for patients with a MELD-Na score of 11 or higher at 1 year after transplant (adjusted hazard ratio, 0.64; 95% CI, 0.47-0.88; P = .006). At a MELD-Na score of 14-16, mortality decreased by about 50% (aHR, 0.47; 95% CI, 0.34-0.66; P < .001).

The probability of death from a living-donor liver transplant for patients with very low MELD-Na scores (between 6 and 10) was greater than that for patients on the wait list for the first 259 days, at which point the risk of death for both groups was equal. At 471 days, the probability of survival in both groups was equal. As the MELD-Na score increased, both the time to equal risk of death and the time to equal survival decreased, demonstrating that the survival benefit occurs much earlier for patients with a higher MELD-Na score.

Analysis of life-years from transplant showed living-donor transplant recipients gained 13-17 life-years compared to those who didn’t receive one.

“Living-donor liver transplantation is a valuable yet underutilized strategy to address the significant organ shortage and long waiting times on the transplant list in the U.S.,” said Renu Dhanasekaran, MD, PhD, assistant professor of gastroenterology and hepatology at Stanford (Calif.) University.

Dr. Dhanasekaran, who wasn’t involved with this study, also welcomed the finding that living-donor liver transplantation can benefit patients with low MELD-Na scores, even below the expected cutoff at 15. According to the study authors, previous research had suggested benefit would be seen only at MELD-Na 15 and above.

“In my practice, I have several patients whose symptoms are out of proportion to their MELD score, and data like this will convince them and their potential donors to avail a transplant at an earlier stage,” she said.

The findings challenge the current paradigm around the timing of referral for a liver transplant and may have ramifications for allocation policies for deceased donors, the study authors wrote. The data can also help to contextualize risk-benefit discussions for donors and recipients.

“Donating a part of one’s liver to save a patient suffering from end-stage liver disease is an incredible act of selfless love,” Dr. Dhanasekaran said. “I hope strong positive data from studies like this one encourage more donors, patients, and transplant centers to expand the use of [living-donor liver transplant].”

The authors reported no grant support or funding sources for this study. One author disclosed being married to the current chair of the United Network for Organ Sharing’s Liver and Intestinal Organ Transplantation Committee. No other conflicts of interest were reported. Dr. Dhanasekaran reported no relevant disclosures.

Living-donor liver transplant recipients gained an additional 13-17 years of life, compared with patients who remained on the wait list, according to a retrospective case-control study.

The data suggest that the life-years gained are comparable to or greater than those conferred by either other lifesaving procedures or liver transplant from a deceased donor, wrote the researchers, led by Whitney Jackson, MD, assistant professor of gastroenterology and medical director of living-donor liver transplantation at the University of Colorado Anschutz Medical Campus.

“Despite the acceptance of living-donor liver transplant as a lifesaving procedure for end-stage liver disease, it remains underused in the United States,” the authors wrote in JAMA Surgery. “This study’s findings challenge current perceptions regarding when the survival benefit of a living-donor transplant occurs.”

Dr. Jackson and colleagues conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database for 119,275 U.S. liver transplant candidates and recipients from January 2012 to September 2021. They assessed the survival benefit, life-years saved, and the Model for End-Stage Liver Disease incorporating sodium levels (MELD-Na) score at which the survival benefit was obtained, compared with those who remained on the wait list.

The research team included 116,455 liver transplant candidates who were 18 and older and assigned to the wait list, as well as 2,820 patients who received a living-donor liver transplant. Patients listed for retransplant or multiorgan transplant were excluded, as were those with prior kidney or liver transplants.

The mean age of the study participants was 55 years, and 63% were men. Overall, 70.2% were White, 15.8% were Hispanic or Latinx, 8.2% were Black or African American, 4.3% were Asian, 0.9% were American Indian or Alaska Native, and 0.2% were Native Hawaiian or Pacific Islander. The most common etiologies were alcoholic cirrhosis (23.8%) and nonalcoholic steatohepatitis (15.9%).

Compared with patients on the wait list, recipients of a living-donor liver transplant were younger, more often women, more educated, and more often White. A greater proportion of transplant recipients had a primary etiology of nonalcoholic steatohepatitis (19.8%) and cholestatic liver disease (24.1%). At wait list placement, one-third of candidates had a MELD-Na score of 14 or higher.

The research team found a significant survival benefit for patients receiving a living-donor liver transplant based on mortality risk and survival scores. The survival benefit was significant at a MELD-Na score as low as 11, with a 34% decrease(95% confidence interval [CI], 17.4%-52.0%) in mortality compared with the wait list. In addition, mortality risk models confirmed a survival benefit for patients with a MELD-Na score of 11 or higher at 1 year after transplant (adjusted hazard ratio, 0.64; 95% CI, 0.47-0.88; P = .006). At a MELD-Na score of 14-16, mortality decreased by about 50% (aHR, 0.47; 95% CI, 0.34-0.66; P < .001).

The probability of death from a living-donor liver transplant for patients with very low MELD-Na scores (between 6 and 10) was greater than that for patients on the wait list for the first 259 days, at which point the risk of death for both groups was equal. At 471 days, the probability of survival in both groups was equal. As the MELD-Na score increased, both the time to equal risk of death and the time to equal survival decreased, demonstrating that the survival benefit occurs much earlier for patients with a higher MELD-Na score.

Analysis of life-years from transplant showed living-donor transplant recipients gained 13-17 life-years compared to those who didn’t receive one.

“Living-donor liver transplantation is a valuable yet underutilized strategy to address the significant organ shortage and long waiting times on the transplant list in the U.S.,” said Renu Dhanasekaran, MD, PhD, assistant professor of gastroenterology and hepatology at Stanford (Calif.) University.

Dr. Dhanasekaran, who wasn’t involved with this study, also welcomed the finding that living-donor liver transplantation can benefit patients with low MELD-Na scores, even below the expected cutoff at 15. According to the study authors, previous research had suggested benefit would be seen only at MELD-Na 15 and above.

“In my practice, I have several patients whose symptoms are out of proportion to their MELD score, and data like this will convince them and their potential donors to avail a transplant at an earlier stage,” she said.

The findings challenge the current paradigm around the timing of referral for a liver transplant and may have ramifications for allocation policies for deceased donors, the study authors wrote. The data can also help to contextualize risk-benefit discussions for donors and recipients.

“Donating a part of one’s liver to save a patient suffering from end-stage liver disease is an incredible act of selfless love,” Dr. Dhanasekaran said. “I hope strong positive data from studies like this one encourage more donors, patients, and transplant centers to expand the use of [living-donor liver transplant].”

The authors reported no grant support or funding sources for this study. One author disclosed being married to the current chair of the United Network for Organ Sharing’s Liver and Intestinal Organ Transplantation Committee. No other conflicts of interest were reported. Dr. Dhanasekaran reported no relevant disclosures.