Alfosbuvir plus Daclatasvir for Treatment of Chronic Hepatitis C Virus Infection in China.

Introduction: A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection.

Gene body hypomethylation of pyroptosis-related genes NLRP7, NLRP2, and NLRP3 facilitate non-invasive surveillance of hepatocellular carcinoma.

Programmed cell death (PCD) resistance is a key driver of cancer occurrence and development. The prognostic relevance of PCD-related genes in hepatocellular carcinoma (HCC) has attracted considerable attention in recent years. However, there is still a lack of efforts to compare the methylation status of different types of PCD genes in HCC and their roles in its surveillance.

Intestinal BMP-9 locally upregulates FGF19 and is down-regulated in obese patients with diabetes.

Bone morphogenetic protein (BMP)-9, a member of the TGFβ-family of cytokines, is believed to be mainly produced in the liver. The serum levels of BMP-9 were reported to be reduced in newly diagnosed diabetic patients and BMP-9 overexpression ameliorated steatosis in the high fat diet-induced obesity mouse model. Furthermore, injection of BMP-9 in mice enhanced expression of fibroblast growth factor (FGF)21.

Kuhuang injection exerts a protective effect by activating PPAR-γ in an model of chlorpromazine-induced cholestatic liver injury constructed by tissue engineering.

Context: Kuhuang (KH) injection is a widely used anticholestatic drug in the clinic and the mechanisms are still unclear.

Objective: This study uses a new 3D tissue-engineered (TE) liver platform to study the ability of kuhuang to ameliorate liver injury induced by chlorpromazine (CPZ) and the possible mechanisms involved.

Materials And Methods: The TE livers ( = 25) were divided into 5 groups ( = 5 livers/group) as 3D, 3D + CPZ, 3D + CPZ + KH, 3D + CPZ + GW9662 (a PPARγ inhibitor) and 3D + CPZ + KH + GW9662.

A novel machine learning-based radiomic model for diagnosing high bleeding risk esophageal varices in cirrhotic patients.

Background And Aim: To develop and validate a novel machine learning-based radiomic model (RM) for diagnosing high bleeding risk esophageal varices (HREV) in patients with cirrhosis.

Methods: A total of 796 qualified participants were enrolled. In training cohort, 218 cirrhotic patients with mild esophageal varices (EV) and 240 with HREV RM were included to training and internal validation groups.

Hepatic stellate cell mediates transcription of TNFSF14 in hepatocellular carcinoma cells via HS/CSE-JNK/JunB signaling pathway.

Hepatic stellate cells (HSC) and hydrogen sulfide (HS) both play important roles in the development of hepatocellar carcinoma (HCC). Whereas, in the microenvironment of HCC, whether HSC participate in regulating the biological process of HCC cells by releasing HS remains elusive. In vitro, Flow cytometry (FCM), CCK-8, RNA-sequencing, Western blotting, RT-qPCR, immunofluorescence and ChIP assays were carried out in the HCC cells to investigate the effect of HS on biological functions and JNK/JunB-TNFSF14 signaling pathway.

Efficacy and safety of alfosbuvir plus daclatasvir in Chinese patients with hepatitis C virus genotypes 1, 2, 3, and 6 infection: An open-label, phase 2 study.

Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. Our previous studies indicated that alfosbuvir monotherapy was well-tolerated and druggable in healthy subjects and HCV-infected patients. Here, we evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV genotype 1, 2, 3 or 6.

infection and peptic ulcer disease in cirrhotic patients: An updated meta-analysis.

Background: Peptic ulcer (PU) is more prevalent in patients with liver cirrhosis. The role of () infection in the pathogenesis of PU in patients with cirrhosis is still not elucidated.

Aim: To perform a meta-analysis on the prevalence of infection and PU and their association in liver cirrhosis patients.

Relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease: What should we expect from a meta-analysis?

Background: The relationship between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) is a matter of debate. Although it has been studied in many observational studies, the results remain controversial.

BMP9 promotes methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in non-obese mice by enhancing NF-κB dependent macrophage polarization.

Our previous study confirmed that bone morphogenetic protein 9 (BMP9) participated in the development of nonalcoholic steatohepatitis (NASH) by affecting macrophage polarization. The focus of this study was to further confirm the role of macrophages in BMP9-mediated NASH and to analyze the underlying mechanism. In vivo, mice that were administered adeno-associated viral (AAV) vectors containing a null transgene (AAV-null) or the BMP9 transgene (AAV-BMP9) were divided into methionine- and choline-deficient (MCD) and control diet (CD) groups, and they were administered either control liposomes or clodronate liposomes via tail vein injection, the latter to deplete macrophages.

Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing.

Background: Circulating cell-free DNA (cfDNA) methylation has been demonstrated to be a promising approach for non-invasive cancer diagnosis. However, the high cost of whole genome bisulfite sequencing (WGBS) hinders the clinical implementation of a methylation-based cfDNA early detection biomarker. We proposed a novel strategy in low-pass WGBS (~ 5 million reads) to detect methylation changes in circulating cell-free DNA (cfDNA) from patients with liver diseases and hepatocellular carcinoma (HCC).

Computed tomography liver stiffness measurement and magnetic resonance imaging in evaluating esophageal varices in cirrhotic patients: A systematic review and meta-analysis.

Background: Computed tomography (CT), liver stiffness measurement (LSM), and magnetic resonance imaging (MRI) are non-invasive diagnostic methods for esophageal varices (EV) and for the prediction of high-bleeding-risk EV (HREV) in cirrhotic patients. However, the clinical use of these methods is controversial.

Aim: To evaluate the accuracy of LSM, CT, and MRI in diagnosing EV and predicting HREV in cirrhotic patients.

Noninvasive chimeric DNA profiling identifies tumor-originated HBV integrants contributing to viral antigen expression in liver cancer.

Background: Host genome integration of HBV sequence is considered to be significant in HBV antigen expression and the development of hepatocellular carcinoma (HCC).

Method: We developed a probe-based capture strategy to enrich integrated HBV DNA for deep-sequencing analysis of integration sites in paired patient samples derived from tumor, liver tissue adjacent to tumor, saliva and plasma, as a platform for exploring the correlation, significance and utility of detecting integrations in these sample types.

Results: Most significantly, alpha fetoprotein levels significantly correlated to the amounts of integrations detected in tumor.

Recommendations on the Diagnosis and Initial Management of Acute Variceal Bleeding and Hepatorenal Syndrome in Patients with Cirrhosis.

Cirrhosis is a serious and life-threatening condition which imposes a significant socioeconomic burden on affected individuals and healthcare systems. Cirrhosis can result in portal hypertension, which may lead to major complications, including acute variceal bleeding and hepatorenal syndrome. Without prompt treatment, these complications may be life-threatening.

Clinical features of idiopathic portal hypertension in China: A retrospective study of 338 patients and literature review.

Background And Aim: Idiopathic portal hypertension (IPH) refers to a relatively rare condition characterized by intrahepatic portal hypertension in the absence of underlying disease such as liver cirrhosis.

Methods: We retrospectively reviewed 338 patients with IPH that were diagnosed at the pathological consultation center of our hospital.

Results: The ratio of male to female patients was 1:1.

Sofosbuvir plus ribavirin with or without peginterferon for the treatment of hepatitis C virus: Results from a phase 3b study in China.

Background And Aim: Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6.

Methods: Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility.

Effect of hepatic steatosis on the progression of chronic hepatitis B: A prospective cohort and study.

Aim: To characterize the effect of hepatic steatosis (HS) on the progression of chronic hepatitis B.

Methods: A total of 162 chronic hepatitis B (CHB) patients confirmed by liver biopsy were involved in this study. All subjects were prospectively followed-up for 5 years in real-life clinical practice.

Utility and safety of tolvaptan in cirrhotic patients with hyponatremia: A prospective cohort study.

Unlabelled: Introduction and aim. Hyponatremia is common in patients with decompensated cirrhosis and is associated with increased mortality. Tolvaptan, a vasopressor V2 receptor antagonist, can increase free water excretion, but its efficacy and safety in cirrhotic patients remain unclear.

The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis.

Background: The purpose of this study was to assess the efficacy and safety between tenofovir and entecavir in the treatment of CHB and HBV related cirrhosis through Meta-analysis. Methods The electronic databases of PubMed, the Cochrane Library, Nature, CNKI and WanFang data were searched. The key words were: ("tenofovir", "entecavir") and ("Chronic Hepatitis B" or "CHB") and "Liver cirrhosis".

Key role of hepatitis B virus mutation in chronic hepatitis B development to hepatocellular carcinoma.

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). The HBV mutations, which include point mutation, deletion, insertion and truncation mutation of HBV gene in 4 open reading frames (S, C, P, X), are closely associated with HCC pathogenesis. Some mutations accumulated during chronic HBV infection could be regarded as a biomarker to predict the occurrence of HCC.

Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through ERK signaling pathway.

Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is frequently upregulated in hepatocellular carcinoma (HCC). However, how GPC3 contributes to the progress of HCC is largely unclear. The present study investigated the association between GPC3 expression and HCC clinicopathological characteristics, and particularly focused on the role and underlying mechanisms of GPC3 in HCC epithelial-mesenchymal transition (EMT).

N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice.

Acute lung injury (ALI) is the leading cause of death in intensive care units. Extracellular histones have recently been recognized to be pivotal inflammatory mediators. Heparin and its derivatives can bind histones through electrostatic interaction.

Antiviral drug resistance increases hepatocellular carcinoma: a prospective decompensated cirrhosis cohort study.

Aim: To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.

Methods: Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort. With two years of follow-up, 198 patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed.