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Our October 2023 hepatology month in review features phase 2/3 data, updates in the hepatology pipeline, and other top news.
For hepatologists and those involved in the care of liver diseases, the month of October 2023 was characterized by news in NAFLD and various hepatic pipeline items. To celebrate the advances and other top news in the world of hepatology, our October 2023 Hepatology Month in Review spotlights 7 pieces of content examining topics ranging from odevixibat for Alagille syndrome to the role of insulin resistance for detecting lean NAFLD.
Among our most popular content during the month of October was an article and video highlighting new data from a phase 2a trial of HU6 for patients with NAFLD and elevated BMI. A randomized, double-blind, placebo-controlled trial, the phase 2a study examined changes in liver fat content with HU6 150 mg, HU6 300 mg, and HU6 450 mg in patients with NAFLD and elevated BMI. Results of the trial suggested 61% of patients treated with HU6 had at least a 30% reduction in liver fat from baseline to day 61, with greater responder rates in the 300 mg (71%) and 450 mg (72%) doses.
The editorial team of HCPLive Hepatology sat down with primary investigator Mazen Noureddin, MD, MHSc, medical director of the Houston Research Institute, for further insight into the study’s findings and their greater implications for the treatment of NAFLD, especially in patients with an increased BMI.
A pooled analysis of data from the phase 3 ASSERT and ASSERT-EXT trials provided further insight into odevixibat’s impact on changes to hepatic parameters in patients with Alagille syndrome. Results suggested the treatment was linked to increased mean levels of serum aminotransferases (ALTs) and significant improvements in patients’ pruritus outcomes with no concurrent increases in total bilirubin.
Post-hoc data from the phase 3 ENHANCE trial showed a dose-dependent decrease in interleukin 31 (IL-31) cytokine among patients with primary biliary cholangitis (PBC) treated with seladelpar, further conveying a correlation between reduced serum IL-31 and improved pruritus. HCPLive Hepatology sat down with study investigator Andreas Kremer, MD, PhD, MHBA, head of hepatology at the department of gastroenterology and hepatology at the University Hospital Zurich in Switzerland, for additional insight about the latest ENHANCE data and the evolving understanding of seladelpar’s benefit in patients with PBC.
“It is of note to report that this phase 3 study was early terminated, due to some histological findings in the NASH trial, which was running in parallel. And this limits a little bit the interpretation of the data, because we in particular could only investigate 3 months of therapy. But still, these 3 months clearly indicated a strong treatment response in regard to alkaline phosphatase, for example, as a surrogate marker of disease progression and PBC,” said Kremer in a Q&A.
Patients with alcohol-associated liver disease may benefit from an alcohol use disorder diagnosis and at least 1 prescription for medication. Findings from a retrospective cohort study highlighted improvement in clinical outcomes and a reduced risk of mortality among patients with a diagnosis of alcohol abuse at index and who were prescribed 1 or more alcohol use disorder medications (both P < .001).
Obesity is present in 50% to 90% of patients diagnosed with NAFLD, but the condition can also affect individuals with a normal weight and BMI. Coined as lean NAFLD, this disease subset often goes undetected due to normal liver enzyme levels and the absence of diabetes among affected patients. Findings from this study supported the use of insulin resistance as an independent predictor of lean NAFLD, validating the clinical utility of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) model.
“This study demonstrated that insulin resistance is a robust independent predictor of lean NAFLD and provides, albeit indirect, evidence to support the role of insulin resistance in the pathogenesis of lean NAFLD. HOMA-IR may help clinicians quickly identify lean patients without diabetes who could benefit from NAFLD screening. Yet, its low positive predictive value limits its diagnostic utility,” wrote investigators.
Treatment with direct-acting antivirals (DAAs) has revolutionized the treatment of hepatitis C virus, with new data pointing to its added benefit on fibrosis regression. In this retrospective cohort study, liver fibrosis regression was observed in 56.9% of patients after 3 years of DAA treatment, with improvement from F3/F4 at treatment to F2 or less during the study seen among 27.8% of participants. Investigators noted age at the time of treatment (odds ratio [OR], 1.359; 95% confidence interval [CI], 1.055–1.751; P = .017) and fibrosis stage (OR, 2.555; 95% CI, 1.864–3.503; P < .001) were associated with liver fibrosis regression.