Hepatology Month in Review: September 2024

With a busy conference season right around the corner, September was a fitting start to what is sure to be a busy fall in the field of hepatology. As the final months of 2024 approach, the past few weeks have seen lots of hepatic pipeline movement, a plethora of new research across a range of liver-related diseases, and the first of many hepatology conferences taking place this fall, all of which we spotlight in this hepatology month in review.

In the Pipeline

HERALD: ALG-055009 Demonstrates Liver Fat Reduction in Phase 2a MASH Study

The hepatology community saw the approval of the first drug for metabolic-dysfunction associated steatohepatitis (MASH) earlier this year with resmetirom (Rezdiffra), but pipeline movement throughout the rest of the year has made it clear that more MASH approvals can be expected in the near future. ALG-055009 is one of many agents progressing through the MASH pipeline, with data from the phase 2a HERALD study of the thyroid hormone receptor beta (THR-β) agonist highlighting its statistically significant reductions in liver fat at week 12.

“The robust improvements in liver fat and other clinically relevant biomarkers, such as lipoprotein (a), demonstrate why potency and PK are pertinent when designing molecules aimed at improving patient outcomes,” Rohit Loomba, MD, MHSc, chief of the division of gastroenterology and hepatology at the University of California, San Diego, said in a press release. “This has been an exciting year for the MASH space, which continues with this excellent data from Aligos’ ALG-055009, which has the potential for not only improvement in resolution of MASH, but also fibrosis improvement. In addition, it has potential to improve cardiovascular risk if the non-invasive tests (NIT) data are confirmed in future trials.”

Positive Phase 2a Data Suggest Disease-Modifying Potential of CNP-104 in PBC

Ending September on a high note and building upon what has been an unprecedented couple of month in primary biliary cholangitis (PBC) with the approvals of 2 new second-line therapies since June, new phase 2a data from COUR Pharmaceuticals suggests CNP-104 may be on its way to becoming yet another treatment option in the growing PBC armamentarium. Unlike current therapies, it aims to address the root cause of PBC by inducing tolerance to pathogenic activated PDC-E2 T-cells driving inflammation in bile ducts, leading to improvement in clinical outcomes of liver health.

All Eyes on OCA in PBC

European Commission Revokes Obeticholic Acid (Ocaliva) CMA for Primary Biliary Cholangitis

On September 3, 2024, the European Commission revoked the conditional marketing authorization (CMA) of obeticholic acid (Ocaliva) in Europe for the second-line treatment of patients with PBC based on a June 2024 recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) following a non-pharmacovigilance Article 20 procedure to reassess the benefit-risk profile of the medicine in PBC. The revocation came mere weeks ahead of the October 15, 2024, PDUFA date for obeticholic acid in the US.

Nancy Reau, MD: Obeticholic Acid’s Future in PBC After FDA Advisory Committee Meeting

Ahead of the October 15, 2024, PDUFA date, a September 13, 2024, US Food and Drug Administration Gastrointestinal Drug Advisory Committee meeting yielded a negative opinion on the verification of obeticholic acid’s benefit on clinical outcomes in PBC as well as its benefit versus risk profile. For additional insight into the significance of this opinion and what it could mean to no longer have obeticholic acid as a treatment option for patients, the editorial team of HCPLive Hepatology sat down with Nancy Reau, MD, associate director of solid organ transplantation and section chief of hepatology at Rush University Medical Center.

Risk in Hepatic Diseases

MASLD, MetALD Linked to Increased Risk of Liver, Gastrointestinal Cancers

New research suggests an important association between steatotic liver disease (SLD) and cancer, with study findings highlighting an increased risk of certain cancers in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD). Compared with those without SLD, patients with MASLD, MetALD, and other combination etiology had a greater risk of developing liver cancer and extrahepatic cancer, particularly gastrointestinal cancer.

MASLD Associated with Greater Risk of Serious Bacterial Infection Requiring Hospitalization

MASLD is associated with an increased risk of serious bacterial infections requiring in-hospital or emergency department care, according to findings from this study. The meta-analysis of aggregate data on more than 26 million adults from 8 observational studies suggests the importance of clinician vigilance regarding infection in their patients with MASLD and the need for preventive measures in this patient population.

New Model Predicts the Hepatocellular Carcinoma Risk in Chronic Hepatitis B

The Revised REACH-B, a new predictive model, outperformed a previous model in predicting the risk of hepatocellular carcinoma in noncirrhotic patients with chronic hepatitis B, offering higher clinical utility compared with the previous REACH-B model.

MetALD Associated with 30% Greater Risk of Cancer-Related Mortality than MASLD

Findings from this study suggest patients with MetALD may be at a greater risk of cancer-related mortality compared to those with MASLD. Leveraging National Health and Nutrition Examination Survey (NHANES) data for more than 5000 patients with SLD, the longitudinal cohort study found those with MetALD had a 30% increased risk of cancer-related mortality compared to those with MASLD.

Gastroenterology and Hepatology Advanced Practice Providers (GHAPP) Conference

Navigating Developments in PBC Treatment, with Allison Moser, MSN, RN, FNP

The PBC treatment landscape has undergone significant developments in the past few months with the addition of 2 new second-line treatment options, seladelpar (Livdelzi) and elafibranor (Iqirvo). At the 2024 annual Gastroenterology and Hepatology Advanced Practice Providers (GHAPP) conference in National Harbor, Maryland, Allison Moser, MSN, RN, FNP, Solid Organ Transplant Lead Advanced Practice Provider at Rush University Medical Center, spotlighted these advancements during her presentation on emerging emerging therapies in the management of PBC, which she reviewed in this interview with HCPLive.

Nutrition’s Role in MASH, Cirrhosis Management, with Tessa Janovsky, PA-C

In this interview with HCPLive, Tessa Janovsky, PA-C, a physician assistant at Arizona Liver Health, reviews the role nutrition plays in MASH and cirrhosis management, describing it as “one of the most important things to discuss with a patient.” The interview was based on her presentation at the 2024 annual (GHAPP conference in National Harbor, Maryland.