Hepatology Month in Review: August 2024

August was a fitting conclusion to what has been a busy summer in hepatology. While summer is often seen as a time for breaks, the field remained active and saw a plethora of developments over the past few months. August was no exception, characterized by pipeline movement expanding the second-line treatment armamentarium in primary biliary cholangitis (PBC) as well as new research about lifestyle factors impacting hepatic disease and hepatitis C virus (HCV) outcomes, all of which we spotlight in this August 2024 hepatology month in review.

In the Pipeline

FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis

Coming on the heels of the accelerated approval of elafibranor (Iqirvo) in June, the FDA granted accelerated approval to another PPAR agonist in August in the form of seladelpar (Livdelzi) for the treatment of PBC. Announced on August 14, 2024, the decision was based on data from the phase 3 RESPONSE study, which showed 62% of patients treated with seladelpar achieved the primary endpoint of composite biochemical response at month 12 versus 20% of patients taking placebo.

According to a release from Gilead, seladelpar's accelerated approval was based on a reduction of ALP, and improvement in survival or prevention of liver decompensation events has not been demonstrated. Accordingly, continued approval of seladelpar may be contingent on verification and description of clinical benefit in confirmatory trial(s). Additionally, seladelpar is not recommended for people who have or develop decompensated cirrhosis.

Related Q&A: Sonal Kumar, MD, MPH: PPAR Agonists in PBC, Advances in Second-Line Therapy

Shifting Treatment Goals, Timelines in Primary Biliary Cholangitis

In light of the recent evolutions in second-line therapy for PBC with the accelerated approval of 2 new PPAR agonists, this 6-part HCPLive special report focuses on the significance of these advances and what their implications might be for the rapidly evolving PBC treatment landscape. The discussion was moderated by Nancy Reau, MD, associate director of solid organ transplantation and section chief of hepatology at Rush University Medical Center, and she was joined by panelists Palak Trivedi, MD, PhD, an associate professor and honorary consultant hepatologist and clinical research director for industry engagement at the University of Birmingham, and Gideon Hirschfield, PhD, MB BChir, director of the Autoimmune Liver Disease Program at University Health Network’s Francis Family Liver Clinic and Toronto Centre for Liver Disease and Lily and Terry Horner Chair in Autoimmune Liver Disease Research at the University of Toronto.

Lifestyle Factors in Hepatic Disease

Study Suggests Tolerability of Moderate Alcohol Consumption in Pi*MZ, Pi*ZZ AATD

New research suggests patients with the heterozygous/homozygous Pi*Z alpha-1 antitrypsin variant of AATD may be able to safely consume moderate amounts of alcohol without a significant impact on liver-related parameters. Leveraging data from the UK Biobank and the European Alpha 1 liver consortium, the study found moderate alcohol intake resulted in a minor increase in elevated transaminases in Pi*MZ individuals and non-carriers, and moderate alcohol consumption had no impact on liver enzymes in Pi*ZZ participants.

Related: Pavel Strnad, MD: Considerations for Safe Alcohol Consumption in AATD

Stretching, Meditation Reduces Cramp Severity and Improves Sleep Quality

Findings from a recent study suggest stretching and meditation both reduce cramp severity and improve sleep quality in patients with cirrhosis. It enrolled 98 participants with a history of > 4 cramps in the previous month who were randomly assigned in a 1:1 ratio to either stretching or meditation for 35 days, after which the groups were assigned a 1-week training period with an instructional video training for their intervention followed by 28 days of outcome assessment. Results showed both arms had a reduction in cramp severity, improved PGIC scores, and improvement in sleep.

Risky Alcohol Use Does Not Impact HCV Treatment Efficacy But Is Linked to Cirrhosis

Results from OPERA-C, a prospective multicenter study conducted across 26 hospital-based liver clinics in Australia, suggest HCV treatment with DAA therapy is equally efficacious in patients with risky alcohol use compared to those without. Although rates of SVR were equivalent regardless of alcohol use, patients with risky alcohol use had greater rates of cirrhosis and more than one-third of patients with cirrhosis continued to consume alcohol, most of whom were not offered pharmacological therapy for alcohol dependence.

Physical Activity Identified as Critical Factor in Lowering MAFLD Risk

Although a number of variables contribute to one’s risk of developing MAFLD, new research suggests physical activity may be among the most critical lifestyle factors influencing MAFLD risk. Of note, sleep duration and diet were also linked to MAFLD in this NHANES analysis.

Hepatitis C Virus Outcomes

Injecting Drugs Often Leads to HCV Reinfection Which Reduces Over Time

People who inject drugs face a significant risk of HCV reinfection in the period immediately following sustained virologic response (SVR), according to findings from a recent study. Notably, rates of reinfection were greater during the initial post-SVR period and decreased progressively with longer follow-up, highlighting the importance of early intervention to prevent reinfection.

“Clinicians and public health leaders should provide full access to treatment in injecting networks and communities all at once to reduce community viral load through the implementation of simplified algorithms for treatment and decentralized models of care,” investigators wrote. “These data will inform public health strategies to achieve HCV elimination and minimize reinfection through identification of high-risk behaviors and the implementation of appropriate interventions for PWID who require more intensive or frequent follow-up and prompt retreatment.”

DAA Treatment Improves Liver-Related Outcomes, Reduces Fibrosis Burden in HCV

Beyond helping patients achieve HCV cure, direct-acting antiviral treatment may also be associated with improvements in liver-related outcomes and a reduction of fibrosis-based disease burden, according to findings from a recent study. Leveraging patient data from 29 tertiary institutions in South Korea, the study found that along with improved fibrotic burden, DAA treatment was independently associated with a decreased risk of hepatocellular carcinoma, decompensation, and mortality, underscoring the importance of early detection and treatment for reducing fibrosis-based disease burden and improving clinical outcomes.

Early HCV Treatment Discontinuation Does Not Inhibit Sustained Virologic Response

Premature discontinuation of DAA therapy does not preclude treatment efficacy in patients with HCV, according to findings from a new study. Results highlight a 78% SVR rate among patients who discontinued treatment, with similar treatment efficacy observed among patients who were treated for > 4 weeks compared to those who completed therapy. Even patients who discontinued therapy before the end of the second week of treatment experienced therapeutic success, especially those with a low baseline viral load.