Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial.

Background: Denifanstat, an oral fatty acid synthase (FASN) inhibitor, blocks de-novo lipogenesis, a key pathway driving progressive lipotoxicity, inflammation, and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). This study aimed to examine the safety and efficacy of denifanstat for improving liver histology in individuals with MASH and moderate to advanced fibrosis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2b trial was conducted at 100 clinical sites in the USA, Canada, and Poland.

A Phase 1, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Bepirovirsen in Adults with Hepatic Impairment and Healthy Participants (B-Assured).

Bepirovirsen is a developmental antisense oligonucleotide (ASO) for treatment of chronic hepatitis B virus infection. No pharmacokinetic (PK) studies comparing participants with hepatic impairment (HI) and healthy participants (HPs) have been conducted with ASOs. Given the target patient population, characterization of bepirovirsen PK in HI was imperative.

Evaluation of four chatbots in autoimmune liver disease: A comparative analysis.

Introduction And Objectives: Autoimmune liver diseases (AILDs) are rare and require precise evaluation, which is often challenging for medical providers. Chatbots are innovative solutions to assist healthcare professionals in clinical management. In our study, ten liver specialists systematically evaluated four chatbots to determine their utility as clinical decision support tools in the field of AILDs.

The effect of vitamin E and docosahexaenoic acid ethyl ester on Metabolic Dysfunction-Associated steatotic Liver Disease (MASLD)-A randomised, double-blind, placebo-controlled, parallel-group clinical trial (PUVENAFLD).

Aims: We conducted a clinical trial to determine the efficacy of the combination of vitamin E and/or docosahexaenoic acid (DHA) versus placebo in reducing liver fat content after 6 months of intervention in adults with MASLD.

Methods: Adults with MASLD were randomised to one of four treatment arms (vitamin E 1000 mg/daily + DHA 1.89 g/daily or combination arm, vitamin E 1000 mg alone, DHA 1.

Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function.

This phase 1, open-label, three-arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK-935) in participants with hepatic impairment. Participants aged ≥18 to <75 years had moderate (Child-Pugh B) or mild (Child-Pugh A) hepatic impairment or normal hepatic function (matched to hepatic-impaired participants by sex, age, and body mass index). Soticlestat was administered as a single oral 300 mg dose.

Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh A cirrhosis detected by an oral cholate challenge test.

New methods for measuring hepatic improvement in clinical trials and the clinic are needed. One new method, HepQuant SHUNT, detected dose-dependent improvements in hepatic function and portal physiology in the phase 1b study (NCT03842761) of avenciguat, an activator of soluble guanylyl cyclase that is being developed for the treatment of portal hypertension. Herein, we examined whether HepQuant Duo, an easy-to-administer test version, could similarly detect the effects of avenciguat.

Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis.

Background & Aims: Survodutide is a glucagon/glucagon-like peptide-1 receptor dual agonist in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). We investigated the pharmacokinetic and safety profile of survodutide in people with cirrhosis.

Methods: This multinational, non-randomized, open-label, phase I clinical trial initially evaluated a single subcutaneous dose of survodutide 0.

Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis is unclear.

Methods: We conducted a phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial involving participants with biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis.

A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.

Background: Dual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction-associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibrosis are unclear.

Methods: In this 48-week, phase 2 trial, we randomly assigned adults with biopsy-confirmed MASH and fibrosis stage F1 through F3 in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of survodutide at a dose of 2.

Noninvasive Methods for Assessing Liver Fibrosis and Steatosis.

Accurate diagnosis and staging of liver fibrosis is crucial to the individualized management of patients with chronic liver disease. Liver biopsy remains the reference standard for the assessment of steatosis, necroinflammation, and fibrosis. However, over the past decade, there has been an exponential growth in noninvasive tests (NITs) designed to assess liver fibrosis and steatosis.

Safety, pharmacokinetics and pharmacodynamics of obeticholic acid in subjects with fibrosis or cirrhosis from NASH.

Background & Aims: Fibrosis stage is a strong predictor of nonalcoholic steatohepatitis (NASH) outcomes. Two blinded studies evaluated the pharmacokinetics, pharmacodynamics and safety of obeticholic acid (OCA) in subjects with staged NASH fibrosis or cirrhosis.

Methods: Study 747-117 randomized 51 subjects with NASH (fibrosis stages F1-F4) to daily placebo, OCA 10 or OCA 25 mg (1:2:2) for 85 days.

Pivoting to telemedicine in a single-day multidisciplinary liver tumor clinic during COVID-19: the Texas Liver Tumor Center experience.

Cancer guidelines recommend that all patients with hepatocellular carcinoma (HCC) have an evaluation by a multidisciplinary team to assess liver health, stage the cancer, and discuss treatment and palliative care options. Coronavirus disease 2019 (COVID-19) had a catastrophic impact on patients with cancer resulting in increased disease burden due to late diagnosis and treatment delays. Late diagnosis has highlighted the need for the early intervention of palliative care for patients with HCC.

NAFLD: A pretransplant and post-transplant conundrum.

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A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a progressive, inflammatory liver disease with no approved pharmacological treatment. This Phase IIa, double-blind, placebo-controlled, multicentre trial (ClinicalTrials.gov: NCT03166735) investigated pharmacodynamics and safety of BI 1467335, an amine oxidase copper-containing 3 (AOC3) inhibitor, in adults with NASH from Europe and North America.

Efficacy and Safety of Sofosbuvir/Velpatasvir Plus Ribavirin in Patients with Hepatitis C Virus-Related Decompensated Cirrhosis.

A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population.

Safety and pharmacokinetics of BI 685509, a soluble guanylyl cyclase activator, in patients with cirrhosis: A randomized Phase Ib study.

Background: Portal hypertension is a severe complication of cirrhosis. This Phase Ib study (NCT03842761) assessed the safety, tolerability, and pharmacokinetics of soluble guanylyl cyclase activator BI 685509 in patients with mild or moderate hepatic impairment (Child-Pugh [CP] A or B cirrhosis) and healthy volunteers (HVs).

Methods: In this single-center, randomized, placebo-controlled study, patients received BI 685509 (maximum doses: 1, 2, or 3 mg, twice daily [BID]) or placebo for 28 days.

Artificial intelligence-assisted digital pathology for non-alcoholic steatohepatitis: current status and future directions.

The worldwide prevalence of non-alcoholic steatohepatitis (NASH) is increasing, causing a significant medical burden, but no approved therapeutics are currently available. NASH drug development requires histological analysis of liver biopsies by expert pathologists for trial enrolment and efficacy assessment, which can be hindered by multiple issues including sample heterogeneity, inter-reader and intra-reader variability, and ordinal scoring systems. Consequently, there is a high unmet need for accurate, reproducible, quantitative, and automated methods to assist pathologists with histological analysis to improve the precision around treatment and efficacy assessment.

A randomized, double-blind, placebo-controlled trial of aldafermin in patients with NASH and compensated cirrhosis.

Background And Aims: Aldafermin, an engineered analog of the human hormone FGF19, improves liver histology in patients with noncirrhotic NASH; however, its efficacy and safety in compensated cirrhosis is unknown. No drug has yet to demonstrate benefit in the compensated NASH population.

Approach And Results: In this multicenter, double-blind, placebo-controlled, phase 2b trial, 160 patients with compensated NASH cirrhosis were randomized to aldafermin 0.

Management of autoimmune and viral hepatitis in immunotherapy: a narrative review.

Background And Objective: Cancer immunotherapy has firmly established itself as a pillar of cancer care due to its advantages over traditional anti-tumor therapy but also carries limitations due to potential for severe adverse reactions. This review highlights the current understanding and management of patients with autoimmune and viral hepatitis immune in the setting of immune checkpoint inhibitor (ICI) therapy.

Methods: A literature search was conducted on PubMed, Scopus, Google Scholar SEER*Stat databases (from inception to December 2022) using search terms: "immune checkpoint inhibitor", "autoimmune hepatitis", "viral hepatitis", "HBV pathogenesis", "HCV pathogenesis", "HBV reactivation", "HCV reactivation", "cancer immunotherapy", "immune related adverse events", "immune related hepatitis".

Pharmacokinetics, safety, and tolerability of BMS-986263, a lipid nanoparticle containing HSP47 siRNA, in participants with hepatic impairment.

BMS-986263 is a retinoid-conjugated lipid nanoparticle delivering small interfering RNA designed to inhibit synthesis of HSP47 protein, a collagen-specific chaperone protein involved in fibrosis development. This is a phase I, open-label, two-part study evaluating pharmacokinetics and safety of BMS-986263 in participants with hepatic impairment (HI). Part 1 (n = 24) of this study enrolled two cohorts with mild and moderate HI and a separate cohort of age- and body mass index (BMI)-matched participants with normal hepatic function.

Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis.

Background & Aims: Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for the treatment of pre-cirrhotic liver fibrosis due to non-alcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase III REGENERATE trial of OCA for the treatment of NASH with a consensus panel analysis, provide additional histology data in a larger population, and evaluate safety from >8,000 total patient-years' exposure with nearly 1,000 participants receiving study drug for >4 years.

Methods: Digitized whole-slide images were evaluated independently by panels of three pathologists using the NASH Clinical Research Network scoring system.

High sustained virologic response rates, regardless of race or socioeconomic class, in patients treated with chronic hepatitis C in community practice using a specialized pharmacy team.

Approved direct-acting antiviral (DAA) regimens against hepatitis C virus (HCV) can cure nearly all patients; however, socioeconomic disparities may impact access and outcome. This study assesses socioeconomic factors, differences in insurance coverage and the drug prior authorization process in HCV-infected patients managed in community practices partnered with a dedicated pharmacy team with expertise in liver disease. This Institutional Review Board-approved, ongoing study captures data on a cohort of 2480 patients from community practices.