Safety, pharmacokinetics and antiviral activity of ABI-H2158, a hepatitis B virus core inhibitor: A randomized, placebo-controlled phase 1 study.

Treatment for chronic hepatitis B virus infection (cHBV) is mostly indefinite, with new finite-duration therapies needed. We report safety, pharmacokinetics and antiviral activity of the investigational HBV core inhibitor ABI-H2158. This Phase 1a/b study (NCT03714152) had three parts: Part A, participants received a single ascending oral dose of ABI-H2158 (5-500 mg) or placebo; Part B, participants received multiple doses of ABI-H2158 300 mg once (QD) or twice (BID) daily or placebo, for 10 days; Part C, cHBV patients received ABI-H2158 (100, 300, or 500 mg QD or 300 mg BID) or placebo, for 14 days.

Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials.

Background & Aims: Cirrhosis-related complications are a major burden. Rifaximin soluble solid dispersion (SSD) tablets (immediate-release [IR]; sustained extended-release [SER]) were designed to increase rifaximin water solubility. These analyses evaluate dosing for prevention of cirrhosis complication-related hospitalizations/mortality and overt hepatic encephalopathy (OHE) treatment.

Variability and Lability of Ammonia Levels in Healthy Volunteers and Patients With Cirrhosis: Implications for Trial Design and Clinical Practice.

Introduction: Ammonia levels are used to assess hepatic encephalopathy, but their levels are highly variable in clinical practice.

Methods: We studied factors associated with variation in ammonia values in cirrhotic patients without previous hepatic encephalopathy and healthy volunteers (HVs).

Results: Ammonia increased by 12% and 18% at 1 and 2 hour, respectively, after a protein meal in 64 cirrhotic patients (P < 0.

The Effects of Hepatic Steatosis on the Natural History of HBV Infection.

Fatty liver prevalence is increasing and becoming a global health burden. Chronic hepatitis B infection (CHB) is one of the most common chronic viral infections. Steatosis in CHB patients increases risk of cirrhosis and hepatocellular carcinoma.

Safety and efficacy of a fixed-dose combination regimen of grazoprevir, ruzasvir, and uprifosbuvir with or without ribavirin in participants with and without cirrhosis with chronic hepatitis C virus genotype 1, 2, or 3 infection (C-CREST-1 and C-CREST-2, part B): two randomised, phase 2, open-label trials.

Background: There is a need for hepatitis C virus (HCV) therapies with excellent efficacy across genotypes and in diverse populations. Part A of the C-CREST-1 and C-CREST-2 trials led to the selection of a three-drug regimen of grazoprevir (MK-5172; an HCV NS3/4A protease inhibitor; 100 mg/day) plus ruzasvir (MK-8408; an NS5A inhibitor; 60 mg/day) plus uprifosbuvir (MK-3682; an HCV NS5B polymerase inhibitor; 450 mg/day). Part B of the studies tested this combination as a single formulation in different treatment durations in a broader population.

Hepatitis B Virus Infection and Liver Decompensation.

The goal in patients with immune active hepatitis B virus (HBV) infection is to significantly suppress viral replication and prevent progression of fibrosis to cirrhosis and liver decompensation and decrease the incidence of hepatocellular carcinoma. This is achievable by the highly active antivirals, entecavir and tenofovir, which are considered first-line therapy in most patients with immune active hepatitis C virus and after liver transplantation to prevent HBV recurrence. Patients with decompensated cirrhosis should be referred for liver transplantation and treated with first-line antivirals as early as possible, with the goal of achieving complete viral suppression in the shortest time possible.

Management of the patient with SVR.

In the current era of therapy with direct-acting antiviral (DAAs) drugs, achievement of a sustained virological response (SVR) is achievable in ⩾90% of hepatitis C-infected patients. SVR benefits are well-recognized with reductions in rates of liver complications, hepatocellular carcinoma and mortality. Additional benefits include reduced morbidity related to extrahepatic and systemic manifestations of hepatitis C such as renal, dermatologic, and metabolic complications.

Acute-on-chronic liver failure: extracorporeal liver assist devices.

Purpose Of Review: Acute-on-chronic liver failure (ACLF), a syndrome precipitated by acute liver injury in patients with advanced cirrhosis, is associated with multiorgan dysfunction and high rates of mortality. Liver support systems have been developed in an attempt to improve survival of patients with ACLF by providing a bridge until recovery of the native liver function.

Recent Findings: Nonbiological devices such as molecular adsorbent recirculating system (MARS) and fractionated plasma separation and adsorption (Prometheus) are effective in improving severe hepatic encephalopathy and cholestasis, have good safety and tolerability profiles and are frequently employed in patients with ACLD; however, randomized controlled trials (RCTs) failed to show improvement in survival.

Implications of hepatitis C virus infection for behavioral symptoms and activities of daily living.

Hepatitis C virus (HCV) is neurovirulent and has been shown to be associated with neuropsychological (NP) deficits in a subset of infected individuals. Despite these previous findings, little work has been done to examine neurobehavioral symptoms associated with HCV infection. We examined 34 HCV seropositive (HCV+) individuals and 35 healthy comparison participants (HCV-) with the self-rating form of the Frontal Systems Behavior Scale (FrSBe).

Treatment persistence in and cost of therapy for patients with chronic hepatitis C: Peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin.

Purpose: Treatment persistence and cost of therapy for patients with chronic hepatitis C (CHC) treated with peginterferon alfa-2a plus ribavirin and peginterferon alfa-2b plus ribavirin were evaluated.

Methods: This retrospective database analysis used eligibility, pharmacy, and medical claims data from a large U.S.

Impairments in fine-motor coordination and speed of information processing predict declines in everyday functioning in hepatitis C infection.

Research increasingly supports the neurovirulence of chronic infection with the hepatitis C virus (HCV). For example, HCV infection has been associated with neuropsychological impairment in several ability areas, including psychomotor skills. This study aimed to examine whether HCV-associated neuropsychological impairment is predictive of declines in the independent performance of physical (PADLs) and instrumental (IADLs) activities of daily living.

Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis.

Unlabelled: Extracorporeal albumin dialysis (ECAD) may improve severe hepatic encephalopathy (HE) in patients with advanced cirrhosis via the removal of protein or non-protein-bound toxins. A prospective, randomized, controlled, multicenter trial of the efficacy, safety, and tolerability of ECAD using molecular adsorbent recirculating system (MARS) was conducted in such patients. Patients were randomized to ECAD and standard medical therapy (SMT) or SMT alone.

Introduction to the Hepatic Encephalopathy Scoring Algorithm (HESA).

A primary obstacle to early diagnosis and treatment of hepatic encephalopathy (HE) is the lack of a well-validated, standardized assessment method. The purpose of this study was to present preliminary validity data on a new method of grading HE, the Hepatic Encephalopathy Scoring Algorithm (HESA), which combines clinical impressions with neuropsychological performances to characterize HE. Participants were 49 inpatients admitted for complications of end stage liver disease.

Cognitive dysfunction in chronic hepatitis C: a review.

The hepatitis C virus (HCV) is a common blood-borne illness that affects up to 2% of the world's population and almost 4 million Americans. Cognitive impairment, or difficulty with thinking, has become a well-established symptom in persons with end stage liver disease. It was previously assumed that cognitive impairment was a consequence of cirrhosis-associated hepatic encephalopathy.

Contrast-enhanced ultrasound as a predictor of treatment efficacy within 2 weeks after transarterial chemoembolization of hepatocellular carcinoma.

Purpose: To determine whether contrast-enhanced ultrasound (CEUS) can aid in assessing treatment efficacy within the first 2 weeks after transarterial chemoembolization for hepatocellular carcinoma.

Materials And Methods: Contrast-enhanced ultrasound was performed to detect residual tumor blood flow after 42 transarterial chemoembolization procedures in 33 patients who had hepatocellular carcinomas, and the results were compared with final tumor outcome. Twenty-nine CEUS studies were performed within 2 weeks after treatment and the remainder within 1 month.

Liver fibrosis: noninvasive diagnosis with double contrast material-enhanced MR imaging.

Purpose: To retrospectively evaluate the accuracy of double contrast material-enhanced (hereafter double-enhanced) magnetic resonance (MR) imaging depiction of hepatic fibrosis, with histopathologic analysis findings as the reference standard.

Materials And Methods: The institutional review board approved this HIPAA-compliant study and waived the requirement for informed consent. One hundred one patients (58 men, 43 women; mean age +/- standard deviation, 52 years +/- 10) who underwent double-enhanced MR imaging with superparamagnetic iron oxide (SPIO)-enhanced and double-enhanced spoiled gradient-echo (SPGR) sequences between 2001 and 2004 and had a reliable reference standard for the diagnosis of liver fibrosis were included.

Neuropsychological test performance in patients co-infected with hepatitis C virus and HIV.

Objective: To determine the effect of co-infection on neuropsychological performance in relatively healthy hepatitis C virus (HCV)-alone patients when compared with HCV/HIV-co-infected patients.

Design: To test whether the burden of co-infection with HCV and HIV on the central nervous system results in increased cognitive deficits, we tested 47 HCV-alone and 29 HCV/HIV-co-infected patients on a neuropsychological screening battery of tests of attention, concentration and psychomotor speed.

Methods: The neuropsychological test performance of HCV-alone and HCV/HIV-co-infected patients was compared with normative samples.

Biopsychosocial predictors of fatigue in chronic hepatitis C.

Objective: The objective of this study was to investigate the relationship of biopsychosocial variables to fatigue in patients with chronic hepatitis C (CHC) with the goal of identifying areas of possible intervention.

Method: Ninety-four patients with CHC not on antiviral therapy completed a demographic questionnaire and measures of fatigue, health-related quality of life, and depression. Fibrosis stage and relevant medical information were obtained from medical records.

Effect of interferon-alpha on cognitive functioning in patients with chronic hepatitis C.

Treatment with interferon-alpha (IFN-alpha) has been shown to adversely affect cognitive functioning in patients with a variety of medical disorders, but information about the effects of IFN-alpha on cognitive functioning in patients with chronic hepatitis C (CHC) is limited. The purpose of this study was to examine the effects of IFN-alpha on neuropsychological test performance in CHC patients. Participants were 30 patients with CHC, 11 who underwent IFN-alpha therapy and 19 who did not.

Role of growth factors in the treatment of patients with HIV/HCV coinfection and patients with recurrent hepatitis C following liver transplantation.

Hepatitis C (HCV) contributes significantly to the morbidity and mortality of patients coinfected with human immunodeficiency virus (HIV) and those with recurrent hepatitis C after successful liver transplantation. Treatment of hepatitis C in these patient populations, while crucial, can be quite challenging. Baseline cytopenias, in particular, may limit dosing of interferon and/or ribavirin or preclude therapy entirely when standard guidelines are followed.

Induction of apoptosis in human lung cancer cells by curcumin.

Curcumin, a phenolic compound from the rhizome of the plant Curcuma longa has anti-inflammatory, antioxidant and anti-cancer activities. Although the precise mode of action of this compound is not yet elucidated, studies have shown that chemo-preventive action of curcumin might be due to its ability to induce apoptosis and to arrest cell cycle. This study investigated the cellular and molecular changes induced by curcumin leading to the induction of apoptosis in human lung cancer cell lines-A549 and H1299.