Hepatology Month in Review: November 2023

November 2023 was undoubtedly a busy month in hepatology, as expected with The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) having taken place in Boston, Massachusetts from November 10-14. On top of new data presented at the conference, November was characterized by news about the management of hepatitis B and hepatitis C.

Conference Coverage: AASLD The Liver Meeting 2023

Retatrutide Clears Fatty Liver Disease in >85% of Patients with Obesity

Among the top stories in hepatology this month was our coverage of data from an additional analysis of a 48-week phase 2 obesity trial for retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors. Findings presented at The Liver Meeting showed once-weekly 8 mg and 12 mg subcutaneous doses of retatrutide resolved fatty liver disease in >85% of treated patients with MASLD and obesity.

Investigators observed a mean relative liver fat change of -81.4% and -82.4% from baseline to 24 weeks with retatrutide 8 mg and 12 mg, respectively—versus a 0.3% increase in placebo. At 48 weeks, the higher-dosage groups reported changes of -81.7% and -86.0%, versus a 4.6% increase with placebo (P <.001). Another 89% and 93% of patients receiving retatrutide 8 mg and 12 mg, respectively, achieved <5% liver fat at 48 weeks (P <.001).

Seladelpar Improves Markers of Cholestasis, Pruritus in Patients with PBC

Data from the phase 3 RESPONSE trial showed treatment with seladelpar 10 mg resulted in statistically significant and durable improvements in markers of cholestasis and liver injury and improved pruritus in patients with primary biliary cholangitis (PBC) and incomplete response or intolerance to ursodeoxycholic acid.

The trial enrolled 193 patients who were randomly assigned to receive either daily oral seladelpar 10 mg or placebo. Upon analysis, 61.7% of patients achieved the primary composite response endpoint of of ALP <1.67xULN, ALP decrease ≥15% and total bilirubin ≤ULN at month 12 with seladelpar compared to 20% with placebo (P < .0001). The secondary endpoint of ALP normalization occurred in 25% of those receiving seladelpar and 0% receiving placebo (P < .0001).

Seladelpar lowered alanine aminotransferase by 23.5% and gamma-glutamyl transferase by 39.1%, compared to 6.5% and 11.4% for placebo, respectively. The key secondary pruritus endpoint was met at month 6 with seladelpar-treated patients with baseline NRS >4 reporting decreases of 3.2 compared to 1.7 for placebo (P < .005), with improvement of pruritus NRS on seladelpar sustained through month 12 (P < .005).

HCV and HBV

Tatyana Kushner, MD, MSCE: HCV Screening, Treatment, and Elimination

In an interview with HCPLive during The Liver Meeting, Tatyana Kushner, MD, MSCE, associate professor of medicine in the division of liver diseases at the Icahn School of Medicine at Mount Sinai, discussed the White House hepatitis C elimination plan, clinicians’ role in addressing this issue, and disparities in patients affected by HCV.

Can the US Replicate India's Hepatitis C Eradication Model?

In this Q&A with Madhumita Premkumar, MD, associate professor in the department of hepatology at the National Academy of Medical Sciences in India, she discussed real-world data from the Punjab HCV Elimination Model and the effect of cost-efficient direct-acting antiviral (DAA) rollout on a national population’s rate of HCV-related decompensated cirrhosis.

VTP-300 Plus Nivolumab Lowers HBsAG, Shows Potential for HBV Cure Regimen

Interim phase 2b study data showed investigative novel antigen-specific immunotherapy VTP-300 in combination with nivolumab was associated with significant hepatitis B surface antigen (HBsAg) reduction in patients with hepatitis B virus through approximately 4 months, suggesting a potential function cure.

The study enrolled patients from 12 sites in Thailand, Hong Kong, and Taiwan beginning October 2022. Upon analysis, VTP-300 plus low-dose nivolumab was linked to sustained reductions in HBsAg through day 113; particularly among the cohort with ≤200 IU/mL levels at baseline, the combination treatment yielded significant improvement. A majority (54%) of such patients reported >0.5 log decline from day 1, and one-third (31%) reported >1 log decline as well. Overall, 13 (23%) of patients reported a >0.5 log HBsAg reduction at day 113, and 5 (9%) reported a >1 log reduction.

Cirrhotic Patients with HCV Retain Liver Event Risk Despite Treatment Response

A retrospective, observational cohort study of 248 patients treated for hepatitis C found patients with HCV-related cirrhosis remain at substantial risk for liver-related and non-liver-related events, even after achieving sustained therapy response.

Upon analysis, investigators found that 62.7% (n = 37) of patients never had an EGD, 22% (n = 13) had 1 EGD, and 15% (n = 9) had ≥2 EGDs. The study detected esophageal varices in 32% (n = 7) of patients who were screened. Moreover, in terms of HCC with abdominal ultrasounds, data showed 37.3% (n = 22) of patients had no ultrasound performed, 28.8% (n = 17) had 1 ultrasound, and 34% (n = 20) had >2 ultrasounds. Analyses also showed 15.3% of patients had an MRI performed and 18.7% had a CT scan for HCC screening.

In analyzing long-term health outcomes, investigators found 4 (6.8%) patients were diagnosed with HCC, no patients were diagnosed with non-Hodgkin’s lymphoma, 10 patients developed diabetes, 2 patients had a myocardial infarction, and 2 developed thyroid disease. Overall, the team indicated patients with HCV-related cirrhosis remain at substantial risk for developing liver-related and non-liver-related events, despite low rates of surveillance for some outcomes.