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.

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.

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.

NAFLD: A pretransplant and post-transplant conundrum.

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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.

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.

Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis (FALCON 2): A Randomized Phase 2b Study.

Background & Aims: Pegbelfermin is a polyethylene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) with compensated cirrhosis.

Methods: FALCON 2 (NCT03486912) was a randomized (1:1:1:1), double-blind, placebo-controlled study.

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH.

Background & Aims: The LIVIFY trial investigated the safety, tolerability, and efficacy of vonafexor, a second-generation, non-bile acid farnesoid X receptor agonist in patients with suspected fibrotic non-alcoholic steatohepatitis (NASH).

Methods: This double-blind phase IIa study was conducted in two parts. Patients were randomised (1:1:1:1) to receive placebo, vonafexor 100 mg twice daily (VONA-100BID), vonafexor 200 mg once daily (VONA-200QD), or 400 mg vonafexor QD (VONA-400QD) in Part A (safety run-in, pharmacokinetics/pharmacodynamics) or placebo, vonafexor 100 mg QD (VONA-100QD), or VONA-200QD (1:1:1) in Part B.

Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long-term follow-up study.

Background And Aims: This study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus-infected participants treated with glecaprevir- and/or pibrentasvir-containing regimens.

Methods: M13-576, a rollover study, evaluated the durability of SVR in a follow-up period of approximately 3 years after hepatitis C virus genotype 1-6-infected participants received a glecaprevir- and/or pibrentasvir-containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections.

High Sustained Virologic Response Rates of Glecaprevir/Pibrentasvir in Patients With Dosing Interruption or Suboptimal Adherence.

Introduction: Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (based on pill count) in patients prescribed 8- or 12-week G/P, the impact of nonadherence on sustained virologic response at post-treatment week 12 (SVR12), factors associated with nonadherence, and efficacy in patients interrupting G/P treatment.

A Phase 2 Double Blinded, Randomized Controlled Trial of Saroglitazar in Patients With Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH), the clinically aggressive variant of nonalcoholic fatty liver disease, is characterized by hepatocellular injury and inflammation. Patients with NASH are at higher risk of progression to cirrhosis and it is therefore targeted for drug development efforts. Lifestyle modifications and weight loss are the only recommended modalities and no drug is yet approved for the treatment of patients with NASH.

Efficacy and safety of glecaprevir/pibrentasvir in patients with HCV genotype 5/6: An integrated analysis of phase 2/3 studies.

Background & Aims: Hepatitis C virus (HCV) has high genetic diversity with six major genotypes (GT) GT1-6 and global distribution. HCV GT5 and 6 are rare with < 10 million people infected worldwide. Data on direct-acting antiviral use in these rare HCV genotypes are limited.

Long-term safety and efficacy results in hepatitis C virus genotype 1-infected patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in the TOPAZ-I and TOPAZ-II trials.

The 3-DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) has shown high sustained virologic response rates (~95%) in phase 3 clinical trials including >2300 HCV genotype 1-infected patients. Real-world evidence studies have confirmed the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with chronic HCV genotype 1 infection and are consistent with clinical trial results. TOPAZ-I and TOPAZ-II are ongoing phase 3b trials, assessing safety, efficacy and long-term progression of liver disease and clinical outcomes for up to 5 years post-treatment in patients treated with OBV/PTV/r + DSV ± RBV.

Efficacy and safety of glecaprevir/pibrentasvir in renally impaired patients with chronic HCV infection.

Background And Aims: Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). Previously available direct-acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes.

Methods: EXPEDITION-5 is a phase 3 study to evaluate efficacy and safety of the fixed-dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD.

Screening for Nonalcoholic Fatty Liver Disease in the Primary Care Clinic.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) to advanced fibrosis and cirrhosis as well as liver cancer. Despite the significant morbidity associated with NAFLD, there are no global consensus guidelines to screen for liver fibrosis in patients considered high risk, including patients older than 50 years with type 2 diabetes or metabolic syndrome. Multiple therapies are currently being investigated and may soon receive regulatory approval for use in the clinic.

Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infections and Compensated Liver Disease.

Background: Untreated, chronic hepatitis C virus (HCV) infection may lead to progressive liver damage, which can be mitigated by successful treatment. This integrated analysis reports the safety, efficacy, and pharmacokinetics (PK) of the ribavirin-free, direct-acting, antiviral, fixed-dose combination of glecaprevir/pibrentasvir (G/P) in patients with chronic HCV genotype 1-6 infections and compensated liver disease, including patients with chronic kidney disease stages 4 or 5 (CKD 4/5).

Methods: Data from 9 Phase II and III clinical trials, assessing the efficacy and safety of G/P treatment for 8-16 weeks, were included.

Ombitasvir/paritaprevir/ritonavir and dasabuvir with or without sofosbuvir for patients with hepatitis C virus genotype 1 infection who failed a prior course of direct-acting antiviral therapy.

Introduction: Despite high efficacy of current direct-acting antiviral agents (DAAs) in treating chronic hepatitis C virus (HCV) infection, a small portion of patients fail treatment. QUARTZ-I was a phase 2, open-label, multicenter, two-part study that assessed the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) with dasabuvir (DSV) with or without the addition of sofosbuvir (SOF) and/or ribavirin (RBV) in DAA treatment-experienced adults with chronic HCV GT1 infection.

Materials And Methods: Genotype 1 HCV-infected patients with or without compensated cirrhosis had prior treatment failure to any DAA (part 1) or ledipasvir/SOF (part 2).

Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir in Patients With Hepatitis C Virus Genotype 1 or 4 Infection and Advanced Kidney Disease.

Introduction: Hepatitis C virus (HCV) infection is common in patients with end-stage renal disease. We investigated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) ± dasabuvir (DSV) ± ribavirin (RBV) in 2 phase 3, open-label, multicenter studies in patients with stage 4 or 5 chronic kidney disease (CKD).

Methods: RUBY-I, Cohort 2 enrolled treatment-naïve or -experienced patients with HCV genotype (GT) 1a or 1b infection, with or without cirrhosis.

Clinical Practice Approach to Nonalcoholic Fatty Liver Disease by Pediatric Gastroenterologists in the United States.

Objectives: Nonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD.

Methods: We performed structured one-on-one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children.

Daclatasvir and sofosbuvir with ribavirin for 24 weeks in chronic hepatitis C genotype-3-infected patients with cirrhosis: a Phase III study (ALLY-3C).

Background: Optimal treatment for patients with HCV genotype-3 infection and liver cirrhosis remains a medical priority. Daclatasvir+sofosbuvir and ribavirin is a recommended option for such patients, but clinical trial data are lacking for treatment >16 weeks.

Methods: This was a single-arm, Phase III study of daclatasvir+sofosbuvir+ribavirin for 24 weeks in patients with compensated cirrhosis and HCV genotype-3 infection.

Overview of Updated Practice Guidelines for Pediatric Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a form of chronic liver disease that is characterized by excessive fatty infiltration of the liver in the absence of significant alcohol consumption. As in the adult population, the etiology of NAFLD in children has been attributed to genetic predilection, insulin resistance, and obesity. The prevalence of NAFLD in the pediatric population has consistently increased over the past few decades, and it is currently considered the most common chronic liver disease in children.