Plasma eicosanoids as noninvasive biomarkers of liver fibrosis in patients with nonalcoholic steatohepatitis.

Background: Eicosanoid and related docosanoid polyunsaturated fatty acids (PUFAs) and their oxygenated derivatives have been proposed as noninvasive lipidomic biomarkers of nonalcoholic steatohepatitis (NASH). Therefore, we investigated associations between plasma eicosanoids and liver fibrosis to evaluate their utility in diagnosing and monitoring NASH-related fibrosis.

Methods: Our analysis used baseline eicosanoid data from 427 patients with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), and longitudinal measurements along with liver fibrosis staging from 63 patients with NASH and stage 2/3 fibrosis followed for 24 weeks in a phase II trial.

Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials.

Background & Aims: Apoptosis signal-regulating kinase 1 (ASK1) plays a key role in hepatocyte injury, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH). We evaluated the safety and antifibrotic effect of selonsertib, a selective inhibitor of ASK1, in patients with advanced fibrosis due to NASH.

Methods: We conducted 2 randomized, double-blind, placebo-controlled, phase III trials of selonsertib in patients with NASH and bridging fibrosis (F3, STELLAR-3) or compensated cirrhosis (F4, STELLAR-4).

Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial.

Background And Aims: We evaluated the safety and efficacy of cilofexor (formerly GS-9674), a small-molecule nonsteroidal agonist of farnesoid X receptor, in patients with nonalcoholic steatohepatitis (NASH).

Approach And Results: In this double-blind, placebo-controlled, phase 2 trial, 140 patients with noncirrhotic NASH, diagnosed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥8% and liver stiffness ≥2.5 kPa by magnetic resonance elastography (MRE) or historical liver biopsy, were randomized to receive cilofexor 100 mg (n = 56), 30 mg (n = 56), or placebo (n = 28) orally once daily for 24 weeks.

Patients With Nonalcoholic Steatohepatitis Experience Severe Impairment of Health-Related Quality of Life.

Introduction: Although there is substantial evidence suggesting poor health-related quality of life (HRQL) in patients with chronic hepatitis C (CHC), similar data in nonalcoholic steatohepatitis (NASH) have not been fully assessed. The aim is to compare HRQL scores in patients with CHC to those with NASH.

Methods: Matched patients with advanced fibrosis (bridging fibrosis and compensated cirrhosis) due to CHC and NASH completed Short Form-36 (SF-36) questionnaire, Chronic Liver Disease Questionnaire (CLDQ), and Work Productivity and Activity Instrument questionnaire.

Noninvasive Tests Accurately Identify Advanced Fibrosis due to NASH: Baseline Data From the STELLAR Trials.

Accurate noninvasive tests (NITs) are needed to replace liver biopsy for identifying advanced fibrosis caused by nonalcoholic steatohepatitis (NASH). We analyzed screening data from two phase 3 trials of selonsertib to assess the ability of NITs to discriminate advanced fibrosis. Centrally read biopsies from the STELLAR studies, which enrolled patients with bridging fibrosis and compensated cirrhosis, were staged according to the NASH Clinical Research Network classification.