Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy.

Background & Aims: Bepirovirsen, an antisense oligonucleotide targeting pregenomic and mRNA transcripts of HBV, has been conjugated to N-acetyl galactosamine (GSK3389404) to enhance hepatocyte delivery. This dose-finding study was the first to assess GSK3389404 for chronic HBV infection.

Methods: This phase IIa, randomised, double-blind, placebo-controlled, 2-part study was conducted in 22 centres in Asia (NCT03020745).

Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study.

Background: Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA.

Aging impairs fibrosis-4 index after sustained virologic response by direct-acting antivirals in chronic hepatitis C infection.

Introduction And Objectives: Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index.

PNPLA3 and HLA-DQB1 polymorphisms are associated with hepatocellular carcinoma after hepatitis C virus eradication.

Background: Even though both interferon (IFN)-based and direct-acting antiviral (DAA) therapies against hepatitis C virus (HCV) reduce the risk of hepatocellular carcinoma (HCC), post-sustained virological response (SVR) patients remain at elevated risk of HCC.

Methods: A total of 4620 patients who achieved SVR were enrolled in this retrospective cohort study. After excluding patients who had a history of HCC or developed HCC within 1 year and whose follow-up period was less than 1 year and who were positive for HBsAg, we investigated the association between clinical characteristics and HCC development after SVR in the remaining 3771 patients.

Factors affecting the recovery of hepatic reserve after sustained virologic response by direct-acting antiviral agents in chronic hepatitis C virus-infected patients.

Background And Aim: Since the advent of direct-acting antiviral (DAA) therapy, the total eradication of hepatitis C virus has been achievable with the recovery of hepatic reserve after achievement of sustained virologic response (SVR). Hence, here, we examined the factors affecting the recovery of hepatic reserve.

Methods: We followed up 403 patients (male: 164, female: 239; genotype 1: 299, genotype 2: 104; median age: 69 years) for at least 3 years after they achieved SVR to DAA therapy.

The effects of diuretic use and the presence of ascites on muscle cramps in patients with cirrhosis: a nationwide study.

Background: Administration of diuretics and the presence of ascites in patients with cirrhosis were reported to be associated with muscle cramps; however, the clinical evidence is limited. This study aimed to determine whether muscle cramps are a diuretic-induced complication and whether ascites was a factor related to muscle cramp.

Methods: A total of 1064 adult patients with cirrhosis were enrolled from 10 hospitals in Japan between June 2017 and December 2018.

Diminished hepatic IFN response following HCV clearance triggers HBV reactivation in coinfection.

In patients with HBV and HCV coinfection, HBV reactivation leading to severe hepatitis has been reported with the use of direct-acting antivirals (DAAs) to treat HCV infection. Here we studied the molecular mechanisms behind this viral interaction. In coinfected cell culture and humanized mice, HBV replication was suppressed by HCV coinfection.

Bile duct adenoma: imaging features and radiologic-pathologic correlation.

Purpose: This study aimed to reveal characteristic imaging features of bile duct adenoma (BDA) by radiologic-pathologic correlation.

Materials And Methods: We retrospectively analyzed pathological and imaging findings of seven patients with BDA.

Results: The median maximum diameter of BDA was 5.

Evaluation of treatment with zinc acetate hydrate in patients with liver cirrhosis complicated by zinc deficiency.

Aim: In Japan, no zinc preparation had been approved for therapeutic purposes before March 2017. Zinc acetate hydrate was recently approved for the treatment of hypozincemia. We evaluated the efficacy and safety of treatment with zinc acetate hydrate.

IFN-λ3 as a host immune response in acute hepatitis E virus infection.

Background And Aim: Hepatitis E virus (HEV) is mainly transmitted orally, either waterborne or zoonotic foodborne. Intestinal viruses such as rotavirus are known to induce type III interferon (IFN) in the gastrointestinal (GI) tract where type III IFN dominantly functions in comparison with type I IFN. Therefore, the aim of this study is to investigate the significance of type III IFN (IFN-λ3) in acute hepatitis E.

Clinical features of liver cirrhosis patients with muscle cramping: a multicenter study.

Background: There has been a small number of reports mention the clinical features including quality of life (QOL) in liver cirrhosis (LC) patients with muscle cramping and therapeutic efficacy for muscle cramping. We evaluated clinical features of muscle cramping and treatments in such patients.

Patients And Methods: Two-hundred and eighty-nine LC outpatients (70.

Clinical features of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without advanced fibrosis.

Background And Aim: The prevalence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD-HCC) is increasing. Unfortunately, NAFLD frequently develops into HCC without liver cirrhosis. Therefore, we investigated the clinical features of HCC in NAFLD patients without advanced fibrosis.

Cross-over study in hyperammonemia patients for efficacy, safety, and acceptability of a new lactulose preparation (SK-1202) compared to approved drug.

Aim: A novel jelly lactulose preparation (SK-1202) has been developed to improve compliance and reduce the elevation of blood glucose levels in diabetic patients. To compare the equivalence in the efficacy and safety of SK-1202 and an approved commercially available syrup preparation, we undertook a randomized multicenter cross-over study in hyperammonemia patients with liver cirrhosis who were taking lactulose.

Methods: Forty-four patients were enrolled and took each preparation for 2 weeks.

A Data Mining-based Prognostic Algorithm for NAFLD-related Hepatoma Patients: A Nationwide Study by the Japan Study Group of NAFLD.

The prognosis of patients with nonalcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC) is intricately associated with various factors. We aimed to investigate the prognostic algorithm of NAFLD-HCC patients using a data-mining analysis. A total of 247 NAFLD-HCC patients diagnosed from 2000 to 2014 were registered from 17 medical institutions in Japan.

Relationship of muscle cramps to quality of life and sleep disturbance in patients with chronic liver diseases: A nationwide study.

Background & Aims: Although muscle cramps frequently occur in patients with cirrhosis, the importance of muscle cramps remains unclear. The aims of this study were to investigate the relationship of muscle cramps with quality of life (QOL) and sleep disturbance. In addition, this multi-institutional collaborative study in Japan investigated factors associated with muscle cramps in patients with cirrhosis.

Potent viral suppression and improvements in alpha-fetoprotein and measures of fibrosis in Japanese patients receiving a daclatasvir/asunaprevir/beclabuvir fixed-dose combination for the treatment of HCV genotype-1 infection.

Background: In the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3.

Methods: Treatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin.

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan.

Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis.

Background: The once-daily, all oral, RBV-free, pangenotypic direct-acting anti-viral regimen consisting of co-formulated NS3/4A protease inhibitor glecaprevir and NS5A inhibitor pibrentasvir (G/P), demonstrated high rates of sustained virologic response (SVR) in phase 2 and 3 studies outside Japan.

Methods: CERTAIN-1 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in Japanese patients with chronic HCV GT1 infection. Patients without cirrhosis received 8 weeks of G/P or 12 weeks of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r, 25/150/100 mg); patients with cirrhosis received G/P for 12 weeks.

Analysis of hepatitis B surface antigen (HBsAg) using high-sensitivity HBsAg assays in hepatitis B virus carriers in whom HBsAg seroclearance was confirmed by conventional assays.

Aim: We investigated the utility of high-sensitivity hepatitis B surface antigen (HBsAg) assays compared with conventional HBsAg assays.

Methods: Using serum samples from 114 hepatitis B virus (HBV) carriers in whom HBsAg seroclearance was confirmed by conventional HBsAg assays (cut-off value, 0.05 IU/mL), the amount of HBsAg was re-examined by high-sensitivity HBsAg assays (cut-off value, 0.

Pooled analysis of HCV genotype 1 resistance-associated substitutions in NS5A, NS3 and NS5B pre-and post-treatment with 12 weeks of daclatasvir, asunaprevir and beclabuvir.

Background: Daclatasvir (DCV; non-structural [NS]5A inhibitor) plus asunaprevir (ASV; NS3 inhibitor) plus beclabuvir (BCV; non-nucleoside NS5B inhibitor) is an approved regimen for hepatitis C virus (HCV) genotype (GT)-1 treatment in Japan. A comprehensive analysis of pre-treatment and treatment-emergent HCV resistance to this regimen ± ribavirin (RBV) was performed.

Methods: Data were pooled from five Phase 2/3 studies of DCV+ASV+BCV±RBV given for 12 weeks to GT-1a- or GT-1b-infected patients.

The combination of elbasvir and grazoprevir for the treatment of chronic HCV infection in Japanese patients: a randomized phase II/III study.

Background: Elbasvir (EBR) in combination with grazoprevir (GZR) has demonstrated efficacy in patients with hepatitis C virus (HCV) infections in trials primarily conducted in the USA and Europe. We investigated the safety and efficacy of EBR in combination with GZR in Japanese patients with chronic HCV infection, with or without cirrhosis.

Methods: The study was conducted in two parts.

Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 (GT1b) infection: Phase 3 studies.

Background And Aim: Vaniprevir is a macrocyclic hepatitis C virus (HCV) non-structural (NS)3/4A protease inhibitor. The objective of these phase 3 multicenter, open-label trials was to evaluate the safety and efficacy of vaniprevir + peginterferon alfa-2b + ribavirin (PR) in Japanese patients with HCV genotype (GT)1 infection who had previously failed treatment with interferon-based regimens.

Methods: Japanese patients with chronic HCV GT1 were enrolled.

Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection.

Background: DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non-nucleoside NS5B inhibitor), has achieved high rates of sustained virologic response at post-treatment Week 12 (SVR12) in phase 3 studies.

Methods: In this phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for 24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 % genotype 1b).

Results: SVR12 rates ≥95 % were achieved in both treatment-naive (N = 152) and interferon-experienced (N = 65) cohorts treated with DCV-TRIO for 12 weeks and were comparable across patient subgroups, including patients aged ≥65 years and those with cirrhosis.

Successful achievement of sustained virological response to triple combination therapy containing simeprevir in two patients with chronic hepatitis C who had failed asunaprevir:Daclatasvir combination therapy.

Patients 1 and 2 were treatment-naive women who had genotype 1b chronic hepatitis C. Both had IL-28B genotype TT, and amino acid substitutions of core 70 and 91 were both wild type. Search for the presence of resistance-associated variants (RAV) in non-structural (NS)3 and NS5A regions confirmed wild-type D168 and L31, along with Y93H, in both patients.