Activation of immune checkpoint OX40 inhibits HBV replication in a mouse model.

Background & Aims: The costimulatory molecules OX40 and OX40L, members of the tumor necrosis factor (receptor) superfamily, play an important role in viral control through the activation of T cells. We speculate that activating the immune checkpoint OX40 may promote the inhibition of hepatitis B virus (HBV) replication.

Methods: To test this hypothesis, we investigated the expression dynamics of OX40/OX40L and studied the effects of activation of OX40 on HBV replication, and further explored the possible mechanism.

Diammonium glycyrrhizinate ameliorates alcohol-induced liver injury by reducing oxidative stress, steatosis, and inflammation.

Alcohol-induced liver injury (ALI) is a serious global health issue. Diammonium glycyrrhizinate (DG), a pharmaceutical form of glycyrrhizic acid, has been reported to have anti-inflammatory and anti-oxidative stress properties. We investigated the potential hepatoprotective effects of DG against ALI and explored the mechanisms of it.

Biological function of type 1 regulatory cells and their role in type 1 diabetes.

The collapse of immune homeostasis induces type 1 diabetes (T1D). In T1D, uncontrolled immune attacks against islet β cells reduce insulin secretion, resulting in hyperglycaemia and various complications. Type 1 regulatory (Tr1) cell therapy is a promising approach for the treatment of T1D.

System analysis based on weighted gene co-expression analysis identifies SOX7 as a novel regulator of hepatic stellate cell activation and liver fibrosis.

Hepatic stellate cell (HSC) activation is the essential pathological process of liver fibrosis (LF). The molecular mechanisms regulating HSC activation and LF are incompletely understood. Here, we explored the effect of transcription factor SRY-related high mobility group box 7 (SOX7) on HSC activation and LF, and the underlying molecular mechanism.

Soluble immune checkpoints are elevated in patients with primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) is a chronically progressive liver disease mediated by an autoimmune response. The aetiology and pathogenesis of PBC are not fully understood and may be related to immune disorders caused by genetic factors and their interaction with environmental factors. Immune checkpoints play an important role in preventing the occurrence of autoimmunity.

FcγRIIB expression increases during primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a severe disease with unknown aetiology and poor prognosis owing to ineffective treatment. B-cell antibodies play a regulatory role during immune responses; therefore, their role in PBC should not be overlooked. Fcγ receptors (FcγRs) of IgG and cell surface glycoproteins play an important role in autoimmune and infectious disease prevention.

The role of IL-17 in lung cancer growth.

Interleukin 17 (IL-17) is an inflammatory cytokine with multiple roles in immune protection, immunopathology, and inflammation-related tumors. Lung cancer is inflammation-related cancer, and a large number of studies have shown that IL-17 contributes to the metastasis and progression of lung cancer. However, some studies have shown that IL17 inhibits the occurrence of lung cancer.

Liver biopsy of chronic hepatitis B patients indicates HBV integration profile may complicate the endpoint and effect of entecavir treatment.

Aims: Viral integration profiles attract increased interest in the study of HBV-related hepatocellular carcinoma (HCC), but their features in the early stage of infection and changes due to antiviral treatments remain largely unknown.

Methods: Liver biopsies and paired blood samples were obtained from HBeAg-positive patients before and after 48 weeks of entecavir treatment, and a probe-based capture strategy was applied for analyzing the HBV integrations in these samples. Serum HBV markers, including viral DNA, pgRNA, and HBsAg, were longitudinally assessed.

Serum qAnti-HBc combined with ALT and HBsAg predicts significant hepatic inflammation in HBeAg-positive immune active patients.

Background And Aim: Quantitative hepatitis B core antibody (qAnti-HBc) level has been reported to predict significant liver inflammation in treatment-naïve chronic hepatitis B patients. However, little evidence has been revealed that qAnti-HBc alone or with other serum parameters in predicting moderate to severe hepatic inflammation in HBeAg-positive immune active patients treated with entecavir (ETV).

Methods: A total of 142 patients with HBeAg-positive immune active hepatitis were recruited in our study.

miR-654-5p Contributes to the Activation and Proliferation of Hepatic Stellate Cells by Targeting RXRα.

Liver fibrosis (LF) is a major disease that threatens human health. Hepatic stellate cells (HSCs) contribute directly to LF via extracellular matrix (ECM) secretion. Moreover, RXRα is an important nuclear receptor that plays a key regulatory role in HSC activation.

Multiple Regions Drive Hepatitis Delta Virus Proliferation and Are Therapeutic Targets.

Hepatitis Delta Virus (HDV) is the smallest mammalian single-stranded RNA virus. It requires host cells and hepatitis B virus (HBV) to complete its unique life cycle. The present review summarizes the specific regions on hepatitis D antigen (HDAg) and hepatitis B surface antigen (HBsAg) that drive HDV to utilize host cell machinery system to produce three types of RNA and two forms of HDAg, and hijack HBsAg for its secretion and entry.

Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B.

Background: Quantitative hepatitis B core-related antigen (qHBcrAg) has a better correlation with intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) than HBV DNA or hepatitis B e antigen (HBeAg), but data are still lacking for its clinical application.

Aim: The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA (pgRNA), cccDNA, and HBeAg seroconversion.

Methods: This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon nucleos(t)ide analog (NUC)-based therapy (NCT03509688 and NCT03546530).

HDV Seroprevalence in HBsAg-Positive Patients in China Occurs in Hotspots and Is Not Associated with HCV Mono-Infection.

HDV infection causes severe liver disease, the global health burden of which may be underestimated due to limited epidemiological data. HDV depends on HBV for infection, but recent studies indicated that dissemination can also be supported by other helper viruses such as HCV. We used a rapid point-of-care test and an ELISA to retrospectively test for antibodies against the Hepatitis Delta antigen (anti-HDV-Ab) in 4103 HBsAg-positive and 1661 HBsAg-negative, anti-HCV-positive sera from China and Germany.

A randomized dose-escalation study on the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of a novel recombinant human albumin in healthy subjects.

Objective: Recombinant human albumin (rHA) is an alternative to human serum albumin (HSA) for treating ascites in cirrhosis patients. This study was to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics/pharmacodynamics (PK/PD) of rHA in healthy subjects to guide the design for further clinical trials.

Methods: Healthy subjects aged 18-55 years were enrolled in this double-blinded, first-in-human, placebo-controlled single ascending dose (SAD) (1.

Serum HBV RNA correlated with intrahepatic cccDNA more strongly than other HBV markers during peg-interferon treatment.

Background: Serum hepatitis B virus RNA (HBV RNA) has been reported to be a surrogate marker of intrahepatic cccDNA during nucleos(t)ide analogs therapy. However, in HBeAg-positive patients treated with peg-interferon (peg-IFN), whether HBV RNA is superior to other HBV markers in reflecting cccDNA profile is still unclear.

Methods: Serum HBV RNA, HBcrAg, HBV DNA, and HBsAg were longitudinally assessed among 30 HBeAg-positive patients during 48-week peg-IFN treatment.

Timing of DAA Initiation After Curative Treatment and Its Relationship with the Recurrence of HCV-Related HCC.

Hepatitis C virus infection is a major cause of chronic hepatitis, leading to cirrhosis and hepatocellular carcinoma (HCC). Many studies agree that interferon (IFN)-based antiviral therapy can reduce the risk of HCC recurrence in patients with chronic hepatitis C who have achieved a sustained virological response (SVR). The recent introduction of direct-acting antivirals (DAA) has resulted in excitingly high SVR rates.

Validation of the GALAD Model and Establishment of GAAP Model for Diagnosis of Hepatocellular Carcinoma in Chinese Patients.

Purpose: GALAD is a statistical model for estimating the likelihood of having hepatocellular carcinoma (HCC) based on gender, age, AFP, AFP-L3, and PIVKA-II. We aimed to assess its performance and build new models in China, where hepatitis B virus (HBV) is the leading etiology of HCC.

Patients And Methods: We built the GALAD-C model with the same five variables in GALAD, and the GAAP model with gender, age, AFP, and PIVKA-II, using logistic regression based on 242 patients with HCC and 283 patients with chronic liver disease (CLD).

Efficacy of a combination of HBV RNA and HBeAg in predicting HBeAg seroconversion in patients treated with entecavir for 144 weeks.

Background: In some previous studies, serum hepatitis B virus RNA (HBV RNA) was proposed as an HBV viral marker during therapy. However, the dynamic change of HBV RNA, the correlation of HBV RNA with cccDNA, and the combination of HBV RNA with known HBV markers in predicting entecavir (ETV) treatment outcome in the same cohort are rarely reported.

Methods: A total of 111 HBeAg-positive patients were enrolled in our study.

High prevalence of Clonorchis sinensis infections and coinfection with hepatitis virus in riverside villages in northeast China.

In China, the prevalence of Clonorchis sinensis (C. sinensis) infections is only evaluated at the provincial level by national sampling surveys, and data from villages and counties are still lacking. In this study, we conducted a cross-sectional survey in 10 villages located along the Lalin River in northeast China.

IL-33 Inhibits Hepatitis B Virus through Its Receptor ST2 in Hydrodynamic HBV Mouse Model.

Interleukin-33 has been demonstrated to be associated with liver damage. However, its potential value in hepatitis B virus (HBV) infection remains unknown. This study was designed to investigate the role of IL-33 in hydrodynamic HBV mouse model.

Computational analysis of naturally occurring resistance-associated substitutions in genes , , and among 86 subtypes of hepatitis C virus worldwide.

Background And Objective: Direct-acting antivirals (DAA) facing resistance continue to be used in some areas worldwide. Thus, identifying hepatitis C virus (HCV) genotypes/subtypes and loci with certain prevalent resistance-associated substitutions (RASs) deserves attention. We investigated the global and regional frequencies of naturally occurring RASs among all confirmed HCV subtypes (n=86) and explored co-occurring and mutually exclusive RAS pairs within and between genes , , and .

Inosine triphosphate pyrophosphatase polymorphisms are predictors of anemia in Chinese patients with chronic hepatitis C during therapy with ribavirin and interferon.

Background And Aim: Polymorphisms of inosine triphosphate pyrophosphatase (rs1127354 and rs6051702) and interferon lambda 4 (IFLN4) (rs12979860) are indicators of anemia and/or sustained virological response (SVR) in patients with chronic hepatitis C on ribavirin/interferon. The study aims to investigate the associations of rs1127354, rs6051702, and rs12979860 with hemoglobin levels and SVR in patients on ribavirin/interferon.

Methods: Polymorphisms were detected by pyrosequencing.

The association of hepatitis c virus infection status with serum glucose levels.

Background: Hepatitis C virus (HCV) infection is commonly associated with a disturbance of glucose metabolism. However, there have been conflicting reports on whether the clearance of the HCV may be followed by changes of serum blood glucose and insulin resistance. The aim of the present study was to evaluate the impact of HCV and antiviral treatment on serum glucose levels and other glucose metabolism parameters.

Association of Hepatitis C and B Virus Infection with CKD and Impact of Hepatitis C Treatment on CKD.

Hepatitis C virus (HCV) infection greatly increases the risk of nephropathy. In this observational study, we aimed to explore the relationship between viral hepatitis infection and chronic kidney disease (CKD), identify risk factors, and determine the effect of antiviral treatment on CKD in Chinese patients with chronic HCV infection. A total of 2,435 study subjects were enrolled and divided into four groups: the HCV infection, HBV infection, HBV and HCV co-infection, and uninfected control groups.