Hepatology Month in Review: December 2024

As 2024 winds to a close, so does a historic era for the field of hepatology. With 2025 in sight, hepatologists and hepatic researchers sought to end the year on a high note in a fitting conclusion to what has been a groundbreaking 2024 for the study of liver diseases.

December was characterized by multiple US Food and Drug Administration updates, new research in hepatitis B virus (HBV) and hepatitis C virus (HCV), and the latest news in metabolic dysfunction-associated steatohepatitis (MASH), all of which is spotlighted in this December 2024 hepatology month in review.

Hepatic FDA News

FDA Finds Obeticholic Acid (Ocaliva) Linked to Serious Liver Injury in Noncirrhotic PBC

On December 12, 2024, the FDA announced the identification of cases of serious liver injury among patients being treated for primary biliary cholangitis (PBC) with obeticholic acid (Ocaliva) who did not have cirrhosis. The new safety information was announced in an update to a previous FDA Drug Safety Communication in 2021 restricting the use of obeticholic acid in patients with PBC and advanced cirrhosis. Now, findings from an FDA review of postmarket clinical trial data for obeticholic acid show an increased risk of liver injury in patients without cirrhosis.

Tobevibart, Elebsiran Receive FDA Breakthrough Therapy Designation for Chronic HDV

On the same day, Vir Biotechnology announced tobevibart and elebsiran received FDA Breakthrough Therapy designation and European Medicines Agency (EMA) Priority Medicines (PRIME) designation for the treatment of chronic hepatitis delta (CHD). The designations were supported by positive safety and efficacy data from the phase 2 SOLSTICE trial and follow FDA Fast Track designation and EMA Committee for Orphan Medicinal Products (COMP) positive opinion on orphan drug designation earlier this year.

FDA Adds Boxed Warning to Fezolinetant (Veozah) for Liver Injury Risk

On December 16, 2024, the FDA added a Boxed Warning to fezolinetant (Veozah) to highlight the known risk of “rare but serious” liver injury associated with use of the medication. The updated warning was based on the FDA’s review of a postmarketing case of serious liver injury reported to the FDA Adverse Event Reporting System (FAERS) database in a patient who experienced symptoms of fatigue; nausea; itching; yellow eyes and skin; light-colored stools; and dark urine within 40 days of starting fezolinetant. After discontinuing the treatment, the patient’s symptoms gradually went away and blood test values slowly returned to normal.

Viral Hepatitis Research

Bemnifosbuvir, Ruzasvir Regimen Meets Safety, SVR Primary Endpoints in Phase 2 HCV Trial

Atea Pharmaceuticals announced positive results from its phase 2 study of an 8-week bemnifosbuvir and ruzasvir regimen for the treatment of HCV, with the trial meeting its primary endpoints for safety and sustained virologic response at 12 weeks post-treatment (SVR12).

According to a December 4, 2024, press release from Atea, primary endpoint results demonstrated a 98% SVR12 rate in the per-protocol treatment adherent patient population after 8 weeks of treatment with the bemnifosbuvir and ruzasvir regimen, which was generally safe and well-tolerated with no drug-related serious adverse events or treatment discontinuations.

HepB-CpG Offers Superior Seroprotection in People with HIV, Prior HBV Vaccine Nonresponse

The 2- and 3-dose regimens of the HepB-CpG vaccine offer superior seroprotection response compared with 3 doses of the conventional HepB-alum vaccine in people with human immunodeficiency virus (HIV) and prior nonresponse to HBV vaccination, according to findings from the phase 3, open-label, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) Network 5379 B-Enhancement of HBV Vaccination in Persons with HIV (BEe-HIVe) randomized clinical trial.

Immunodeficiency, Injection Drug Use Linked to Failed HCV Treatment in People with HIV

Findings from this study shine light on the efficacy of direct-acting antivirals (DAAs) for the treatment of HCV in people with HIV, highlighting a 95% treatment success rate in this patient population and providing additional insight into factors negatively affecting treatment response.

Leveraging data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), the study found that although unsuccessful HCV treatment with DAAs was uncommon, it was more frequently observed among people with lower CD4+ cell counts, people with HCV genotype 4, and people who reported recently injecting drugs.

What’s New in MASH

Belapectin Misses Primary Endpoint in Phase 3 MASH Cirrhosis, Portal Hypertension Trial

The phase 2b/3 NAVIGATE trial of Galectin Therapeutics’ belapectin in patients with MASH cirrhosis and portal hypertension missed its composite primary endpoint for the prevention of varices, according to a December 20, 2024, press release from the company. Although belapectin in both 2 mg/kg and 4 mg/kg doses reduced the incidence of varices in the intent-to-treat population, the difference over placebo was not statistically significant.

Machine-Learning Models Could Help ID MASH Patients Considered Candidates for Resmetirom

Recent data suggest leveraging artificial intelligence, more specifically metabolomics-based machine learning models, could help revolutionize screening for identifying patients with MASH who would be candidates for treatment with resmetirom (Rezdiffra), the first and only FDA-approved MASH therapeutic.

Results of the study demonstrate the limitations of current noninvasive testing methods for detecting noncirrhotic MASH with moderate-to-severe fibrosis while highlighting the potential of machine learning models to improve the accuracy, sensitivity, and predictive ability of current testing methods.

Study Highlights Real-World Mortality Rates, Factors Increasing Mortality Risk in MASH

An analysis of real-world data for more than 18,000 US patients with MASH sheds light on mortality rates, causes of death, and the impact of biomarkers and socioeconomic factors on mortality rates among this patient population.

Results indicated having an eGFR of less than 60mL/min/1.73m2 (Hazard ratio [HR], 3.01) and having 3 or more metabolic comorbidities (HR, 1.93) were associated with increased mortality. Investigators also highlighted findings pointing to an increased rate of all-cause mortality among those living in the Southern United States relative to their counterparts in the Northeast (HR, 1.56).