What is new in hepatology in 2023?

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

The definition of hepatorenal syndrome has also substantially evolved.⁵ Terminology now acknowledges significant renal impairment at lower creatinine levels than previously used and recognizes the contribution of chronic kidney disease. The FDA approved terlipressin, a potent vasoconstrictor, for the treatment of hepatorenal syndrome with acute kidney injury (HRS-AKI, formerly HRS-Type I).

The AASLD published updates in advanced management of variceal bleeding highlighting intravascular interventions for esophageal, gastric, and ectopic varices. Data support early transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with Child-Turcotte-Pugh (CTP) B or CTP C (< 14 points) within 72 hours of initial bleeding. However, hepatic encephalopathy remains a common complication. A randomized controlled trial demonstrated that rifaximin started 14 days prior to elective TIPS may reduce post-TIPS hepatic encephalopathy by 52%.⁶

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

 

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

The definition of hepatorenal syndrome has also substantially evolved.⁵ Terminology now acknowledges significant renal impairment at lower creatinine levels than previously used and recognizes the contribution of chronic kidney disease. The FDA approved terlipressin, a potent vasoconstrictor, for the treatment of hepatorenal syndrome with acute kidney injury (HRS-AKI, formerly HRS-Type I).

The AASLD published updates in advanced management of variceal bleeding highlighting intravascular interventions for esophageal, gastric, and ectopic varices. Data support early transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with Child-Turcotte-Pugh (CTP) B or CTP C (< 14 points) within 72 hours of initial bleeding. However, hepatic encephalopathy remains a common complication. A randomized controlled trial demonstrated that rifaximin started 14 days prior to elective TIPS may reduce post-TIPS hepatic encephalopathy by 52%.⁶

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

 

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

The definition of hepatorenal syndrome has also substantially evolved.⁵ Terminology now acknowledges significant renal impairment at lower creatinine levels than previously used and recognizes the contribution of chronic kidney disease. The FDA approved terlipressin, a potent vasoconstrictor, for the treatment of hepatorenal syndrome with acute kidney injury (HRS-AKI, formerly HRS-Type I).

The AASLD published updates in advanced management of variceal bleeding highlighting intravascular interventions for esophageal, gastric, and ectopic varices. Data support early transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with Child-Turcotte-Pugh (CTP) B or CTP C (< 14 points) within 72 hours of initial bleeding. However, hepatic encephalopathy remains a common complication. A randomized controlled trial demonstrated that rifaximin started 14 days prior to elective TIPS may reduce post-TIPS hepatic encephalopathy by 52%.⁶

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

 

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.