Hepatology Month in Review: November 2024

With 2025 looming around the corner, November saw the start of a final push to end 2024 strongly with a fitting conclusion to what is sure to be a historic year in the field of hepatology.

The month was characterized by US Food and Drug Administration news, headline clinical trial data, and coverage of a pair of hepatic conferences with the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) 2024 annual meeting and The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD), all of which we spotlight in this November 2024 month in review.

Hepatic Pipeline News

FDA Issues CRL to Obeticholic Acid (Ocaliva), Denies Full Approval for PBC

On November 12, 2024, the FDA issued a Complete Response Letter (CRL) to Intercept Pharmaceuticals’ obeticholic acid (Ocaliva) for the treatment of primary biliary cholangitis (PBC). In the CRL, the FDA informed the company that it is unable to approve the supplemental New Drug Application in its current form, consistent with the outcome of a Gastrointestinal Drugs Advisory Committee meeting held in September 2024 that 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.

“We believe in the totality of evidence supporting OCALIVA and intend to work closely with the FDA on next steps,” Vivek Devaraj, US President and Chairman at Intercept, said in a press release. “We remain committed to patients living with PBC who have limited treatment options.”

ESSENCE: Semaglutide Improves Fibrosis, Resolves Steatohepatitis in MASH

Headline results from the first part of the ongoing phase 3 ESSENCE trial of once-weekly subcutaneous semaglutide 2.4 mg in adults with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis suggest the GLP-1 receptor agonist show the trial achieved its primary endpoints.

Specifically, a statistically significant and superior improvement in liver fibrosis with no worsening of steatohepatitis as well as resolution of steatohepatitis with no worsening of liver fibrosis was observed with semaglutide 2.4 mg compared with placebo.

HCPLive at NASPGHAN 2024

NASPGHAN 2024: PEDFIC Data Highlight Safety of Odevixibat in Pediatric Patients with PFIC

New data from the PEDFIC program presented at NASPGHAN 2024 is providing insight into the safety of odevixibat (Bylvay) for the treatment of cholestatic pruritis in patients with progressive familial intrahepatic cholestasis (PFIC). The analysis focused primarily on treatment-emergent adverse events in the Medical Dictionary for Regulatory Activities System Organ Class (SOC) of gastrointestinal disorders, particularly diarrhea treatment-emergent adverse events.

Results showed 51% of patients experienced a treatment-emergent adverse event within the gastrointestinal disorders SOC, with diarrhea as the most common event, occurring in 24% of patients, all of which were mild or moderate in severity and nonserious, and 90% resolved by the data cutoff.

Machine Perfusion Could Help Address Transplant Crisis for Pediatric Liver Diseases

Data presented at the NASPGHAN 2024 annual meeting is shedding new light on the potential of machine perfusion in pediatric liver transplants, detailing the effect of machine perfusion among a cohort of 22 pediatric patients and indicating use of a machine-perfused marginal graft was not associated with increased mortality in liver transplant patients. Of note, despite this data, investigators suggest further investigation is needed to better understand the optimal patient population for this emerging modality.

Study Finds Most Children with Hep C have Developmental Disorder, Learning Difficulty

Research from a review of medical records data suggests the presence of hepatitis C virus (HCV) could predispose children to neurodevelopmental disorders, with 62% of children with HCV in the study experiencing some neurodevelopmental disorder or learning difficulties.

“Based on these results, we suggest that practitioners who care for children with chronic HCV may have a role in proactively identifying patients with neurodevelopmental difficulties and linking them with appropriate resources,” investigators wrote.

HCPLive at AASLD The Liver Meeting 2024

Vitamin D Deficiency Linked to Worse Autoimmune Hepatitis Outcomes

New research suggests patients with autoimmune hepatitis who are deficient in vitamin D may face worse outcomes, including hospitalizations, intensive care unit admissions, acute hepatic failure, liver transplantation, and mortality.

“Patients with autoimmune hepatitis may benefit from periodic screening for vitamin D deficiency, in accordance with AASLD guidelines, and treatment of individuals with concomitant vitamin D deficiency,” investigators wrote. “Larger prospective cohort studies are warranted to validate these findings.”

ITCH-E: Pruritus Linked to Worse Health-Related Quality of Life in PBC

Adult patients with PBC who also have pruritus face a significantly greater health-related quality of life burden and activity impairment compared with patients who have no/mild itch, according to findings from a recent study. The research shines a new light on the various negative effects of moderate/severe itch in patients with PBC, emphasizing the need for safe and efficacious PBC treatments that can also improve pruritus.

Kris Kowdley, MD: Elafibranor Remains Safe, Efficacious for PBC Through 3 Years

Open-label extension data from the ongoing phase 3 ELATIVE study are providing clinicians with an overview of the long-term benefit of second-line treatment with elafibranor (Iqirvo) for PBC, highlighting sustained improvements in biomarkers of cholestasis and pruritus, stabilization of surrogates for fibrosis, and improvements in pruritus up to 3 years.