Hepatology Review: Advancements in MASH, PBC Treatments and Disease Risk
核心洞察
ALG-055009, a thyroid hormone receptor beta (搜索) agonist, demonstrated statistically significant reductions in liver fat in a Phase 2a study for MASH (搜索), showing promise for MASH resolution and fibrosis improvement.
New Phase 2a data suggests CNP-104 could be a novel treatment for PBC (搜索) by targeting the root cause of the disease, inducing tolerance to pathogenic T-cells and improving liver health.
Research indicates that MASLD (搜索) and MetALD (搜索) are associated with an increased risk of liver and gastrointestinal cancers, emphasizing the need for vigilance and preventive measures.
September marked a dynamic period in hepatology, featuring significant pipeline advancements, new research across liver diseases, and key conference discussions. The field is seeing progress in the treatment of metabolic dysfunction-associated steatohepatitis (MASH (搜索)) and primary biliary cholangitis (搜索) (PBC (搜索)), alongside increased awareness of disease-related risks.
MASH Pipeline Progress
Following the approval of resmetirom (Rezdiffra) for MASH (搜索), ALG-055009 is emerging as a promising agent. Data from the Phase 2a HERALD study highlighted statistically significant reductions in liver fat at week 12 with this thyroid hormone receptor beta (搜索) (THR-β (搜索)) agonist. According to Rohit Loomba, MD, MHSc, the drug has the potential for improvement in resolution of MASH and fibrosis. The results also suggest potential cardiovascular benefits, pending confirmation in future trials.
Potential Disease-Modifying Therapy for PBC
New Phase 2a data from COUR Pharmaceuticals (搜索) indicates that CNP-104 may offer a novel approach to treating PBC (搜索). Unlike current therapies, CNP-104 aims to address the underlying cause of PBC by inducing tolerance to pathogenic activated PDC-E2 T-cells, which drive inflammation in bile ducts. This mechanism could lead to improved clinical outcomes and liver health.
Obeticholic Acid (Ocaliva) Regulatory Changes
The European Commission revoked the conditional marketing authorization for obeticholic acid (Ocaliva) in Europe for PBC (搜索) treatment, following a recommendation from the European Medicines Agency (EMA). This decision was based on a reassessment of the drug's benefit-risk profile. Prior to this, a 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.
Increased Cancer Risk in Steatotic Liver Disease
Research indicates a significant association between steatotic liver disease (SLD) and cancer. Patients with metabolic dysfunction-associated steatotic liver disease (MASLD (搜索)) and MASLD with increased alcohol intake (MetALD (搜索)) face a greater risk of developing liver cancer and extrahepatic cancers, particularly gastrointestinal cancers, compared to those without SLD. Another study found that MetALD was associated with a 30% greater risk of cancer-related mortality than MASLD.
Infection Risk in MASLD
Findings from a meta-analysis suggest that MASLD (搜索) is associated with an increased risk of serious bacterial infections requiring hospitalization or emergency department care. This highlights the importance of clinician vigilance and preventive measures for patients with MASLD.
New Model for Hepatocellular Carcinoma Risk Prediction
The Revised REACH-B, a new predictive model, outperformed a previous model in predicting the risk of hepatocellular carcinoma (搜索) in noncirrhotic patients with chronic hepatitis B, offering higher clinical utility compared with the previous REACH-B model.