Cholinergic Anti-inflammatory Pathway Attenuates Acute Liver Failure Through Inhibiting MAdCAM1/α4β7-mediated Gut-derived Proinflammatory Lymphocytes Accumulation.

Background & Aims: The function of cholinergic anti-inflammatory pathway (CAP) in acute liver failure (ALF) with inflammatory storm remains indefinite. The liver-gut axis has been proved to be crucial for liver homeostasis. Investigation about CAP regulation on liver-gut axis would enrich our understanding over cholinergic anti-inflammatory mechanism.

MAPK p38/Ulk1 pathway inhibits autophagy and induces IL-1β expression in hepatic stellate cells.

In the past, hepatic stellate cells (HSCs) were considered to be noninflammatory cells and to contribute to liver fibrosis by producing extracellular matrix. Recently, it was found that HSCs can also secrete cytokines and chemokines and therefore participate in hepatic inflammation. Autophagy participates in many immune response processes in immune cells.

Vertical transmission of hepatitis B virus: propositions and future directions.

Chronic hepatitis B virus (HBV) infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection. Implementation of hepatitis B vaccine, the foundation to prevent perinatal and horizontal transmission, has reduced the prevalence of HBV by >80%. In countries where the hepatitis B immune globulin (HBIG) is available, such as China and the United States, the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission.

Characteristics of Peripheral Lymphocyte Subsets in Patients With Acute-On-Chronic Liver Failure Associated With Hepatitis B.

Acute-on-chronic liver failure (ACLF) is a rare, but dramatic clinical syndrome. There is substantial evidence suggesting that immunity-mediated inflammation plays an important role in HBV-ACLF. Our aim was to characterize the proportion and cell counts of peripheral blood lymphocyte subsets in acute-on-chronic liver failure patients caused by HBV infection.

Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

Background And Aim: In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China.

Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis.

Acute liver failure (ALF) usually results in hepatocellular dysfunction and coagulopathy and carries a high mortality rate. Hepatic stellate cells (HSCs) are famous for their role in liver fibrosis. Although some recent studies revealed that HSCs might participate in the pathogenesis of ALF, the accurate mechanism is still not fully understood.

Nitric oxide inhibits autophagy and promotes apoptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide. The expression of nitric oxide synthase (NOS) and the inhibition of autophagy have been linked to cancer cell death. However, the involvement of serum nitric oxide (NO), the expression of NOS and autophagy have not been investigated in HCC.

Natural Killer Group 2A Expressed on Both Peripheral CD3CD56NK Cells and CD3CD8T Cells Plays a Pivotal Negative Regulatory Role in the Progression of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

To explore the role of surface receptors natural killer group 2A (NKG2A) and natural killer group 2D (NKG2D) on CD3CD8T cells and CD3CD56NK cells in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), we measured the expression of NKG2A and NKG2D on the surface of these 2 types of circulating cells by flow cytometry in 3 groups. One group consists of 36 patients with chronic hepatitis B (CHB), another one consists of 22 patients with HBV-related ACLF, and the last one has 12 normal controls (NC). The experimental result indicated that there was no significant difference in the proportion of CD3CD8T cells in total lymphocytes between the 3 groups.

Insulin Resistance Predicts Virological Response to Interferon-α in Chronic Hepatitis B Patients.

Goals: To elucidate impact of insulin resistance (IR) on the response to interferon-α (IFN-α) therapy in chronic hepatitis B (CHB) patients.

Background: Metabolic factors influencing the virological response of CHB patients on IFN-α treatment are still unexplored.

Study: Eighty CHB patients were treated with IFN-α for 48 weeks.

Advanced glycation end product (AGE)-induced hepatic stellate cell activation via autophagy contributes to hepatitis C-related fibrosis.

Aims: Advanced glycation end products (AGEs) have been implicated in pulmonary and renal fibrosis. Herein, we investigated whether AGEs are associated with liver fibrosis and examined the underlying mechanism by focusing on hepatic stellate cell (HSC) activation and autophagy induction.

Methods: Liver fibrosis was assessed by transient elastography (FibroScan).

In vitro immunomodulatory activity of interferon alpha on toll-like receptor 9 signaling pathway in chronic hepatitis B.

Interferon alpha (IFN-α) is registered for chronic hepatitis B (CHB) treatment. However, the antiviral mechanism of IFN-α and the biological function of many IFN-α responsive genes have not been fully elucidated. We investigated to determine the regulative effect of IFN-α on toll-like receptor (TLR) 9 signaling in peripheral blood mononuclear cells (PBMCs) from CHB patients in vitro.

A functional variant at miR-34a binding site in toll-like receptor 4 gene alters susceptibility to hepatocellular carcinoma in a Chinese Han population.

Toll-like receptor 4 (TLR4) plays a key role in prompting the innate or immediate response. A growing body of evidence suggests that genetic variants of TLR4 gene were associated with the development of cancers. This study aimed to investigate the relationship of a functional variant (rs1057317) at microRNA-34a (miR-34a) binding site in toll-like receptor 4 gene and the risk of hepatocellular carcinoma.

Psychological stress exerts effects on pathogenesis of hepatitis B via type-1/type-2 cytokines shift toward type-2 cytokine response.

Background: Psychological and physical stress has been demonstrated to have an impact on health through modulation of immune function. Despite high prevalence of stress among patients with hepatitis B virus (HBV) infection, little is known about whether and how stress exerts an effect on the course of hepatitis B.

Methods: Eighty patients with chronic hepatitis B(CHB) completed the Perceived Stress Scale-10(PSS-10) and State-Trait Anxiety Inventory(STAI).

Serum IL-21 levels associated with chronic hepatitis B and hepatitis B-related liver failure.

The aim of the present study was to investigate the role of interleukin (IL)-21 in chronic hepatitis B virus (HBV) infection. IL-21 stimulates T and B cell responses and plays a role in the control of chronic viral infections. Serum IL-21 levels were measured by enzyme immunoassay in 109 patients with chronic HBV infection at various clinical stages, as well as in 19 healthy controls (HCs).

[Combined immunoprophylaxis induces changes in anti-hepatitis B surface protein titer in infants born to mothers with positivity for hepatitis B surface antigen].

Objective: To conduct a prospective randomized controlled trial of infants born to hepatitis B virus (HBV) surface antigen (HBsAg)-positive mothers in order to investigate the dynamic changes in the titer of anti-HBV surface protein (HBS) induced by treatment with combined immunoprophylaxis (200 IU hepatitis B immunoglobulin (HBIG) and 5 or 10 mug yeast recombinant hepatitis B vaccine), to compare the protective effect of 5 and 10 mug hepatitis B vaccine, and to provide an immunization strategy, monitoring mode and booster immunization schedule for the high-risk group.

Methods: Two-hundred-and-sixty-nine infants born to HBsAg positive mothers were given combined immunoprophylaxis at birth, and the venous blood samples (at birth, and 1, 7 and 12 months) were tested for HBV DNA load, and HBsAg and anti-HBS titers.

Results: The overall 1-year protective rate of combined immunoprophylaxis was 95.

Hepatitis B virus infection in clustering of infection in families with unfavorable prognoses in northwest China.

Hepatitis B virus (HBV) infection and its associated liver diseases have characteristics of familial clustering in China. However, the reasons for this are not understood fully. To address this issue, the prevalence HBV infection and the characteristics of unfavorable prognoses in clustering of infection in families in northwest China were investigated.

Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure.

Aim: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).

Methods: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19(th) Conference of the Asian Pacific Association for the Study of the Liver in 2009.

[Relationship between the expression of HBV mRNA in embryos and father-to-infant HBV transmission].

Objective: To investigate father-to-infant transmission of hepatitis B virus (HBV) by detecting HBV mRNA in the IVF embryos with paternal HBV infection.

Methods: We collected 18 discarded IVF embryos (9 cases) with paternal chronic HBV infection, and detected HBV mRNA in the embryos by single-cell RT-PCR.

Results: HBV mRNA positive signals were found in 1 of the 18 embryos with paternal serum HBV positive markers (5.

Correlation of AIM2 expression in peripheral blood mononuclear cells from humans with acute and chronic hepatitis B.

The AIM2 (absent in melanoma 2) protein promotes host defenses against invading viruses and pathogenic bacteria through corresponding adapter molecules leading to the initiation of innate immune responses. We investigated the expression of AIM2 in peripheral blood mononuclear cells (PBMCs) from patients with acute hepatitis B (AHB) and chronic hepatitis B (CHB) during different clinical phases, and analyzed the correlation between AIM2 and clinical profiles in these groups. This study indicated that there is higher expression of AIM2, IL-1β, and IL-18 in AHB compared with expression in CHB.

[Expression of COX-2 and PPARg in the livers of patients with acute on chronic HBV-related liver failure and their relationship with clinic parameters].

Objective: To study the expressions of cyclooxygenase-2 (COX-2) and Peroxisome proliferator-activated receptor gamma (PPARg) in liver of patients with hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF) and their correlation with clinical parameters.

Methods: 35 patients with ACLF, 35 patients with HBV related chronic liver failure (CLF), 27 patients with chronic hepatitis B(CHB) and 15 normal control were enrolled to study the expressions of COX-2 and PPARg in the liver tissues by immunohistochemical staining, and to analyze the correlation of the COX-2 and PPARg levels in liver tissues with clinical parameters.

Results: COX-2 was distinctly expressed in the cytoplasm of the hepatocytes, but PPARg was mostly expressed in the nuclei of the hepatocytes and also could be seen in the cytoplasm.

Asialoglycoprotein receptor interacts with the preS1 domain of hepatitis B virus in vivo and in vitro.

Background: The preS1 domain of the large envelope protein has been identified as an essential viral structure involved in hepatitis B virus (HBV) attachment. However, the cellular receptor(s) for HBV has not yet been identified.

Aims: To identify a cell-surface receptor for HBV, which could elucidate the molecular mechanism of HBV infection.

[Construction of a bait plasmid containing HBV PreS1 gene in a yeast two-hybrid system and evaluation of its toxicity and self-activation].

Objective: To construct a yeast expression vector of hepatitis B virus (HBV) PreS1 gene using the Sos-recruitment system (SRS), and evaluate the effect of the expression product on the growth of the yeast cells and activation of the reporter gene.

Methods: The coding sequence of HBV preS1 was amplified by PCR and cloned into the yeast expression plasmid pSos. The recombinant bait plasmid pSos- PreS1 was verified by sequencing before transformation into competent yeast cells.

Identification of a novel protein binding to hepatitis C virus core protein.

Background: Hepatitis C virus (HCV) core protein is a multi-functional viral protein that interacts with several target proteins of both viral and cellular origin.

Aim And Methods: To gain insight into the mechanism of action of HCV core protein, we used a yeast two-hybrid system to identify the core protein-interacting cellular targets.

Results: A cDNA clone encoding an aspartoacylase was obtained, termed aspartoacylase 3 (ACY3).

[Cellular localization of HCBP1 and its interaction with HCV core protein in vivo].

Objective: To analyze the interaction of hepatitis C virus (HCV) core protein with HCBP1 and observe the expression and cellular localization of HCBP1.

Methods: The cDNA fragments encoding HCV core protein and HCBP1 were amplified by PCR and subsequently cloned into pGEM T vector, respectively. After sequence verification, the two recombined vectors were respectively subcloned into two hybrid plasmids, pM and pVP16.

Not polymorphism but methylation of class II transactivator gene promoter IV associated with persistent HBV infection.

Background: Class II transactivator (CIITA) is the major rate-limiting regulator for expression of class II major histocompability complex (MHC-II). Human CIITA gene expression is controlled by four distinct promoters (pIto pIV).

Objective: To evaluate the relationship among polymorphism and methylation status of CIITA gene promoters and persistent hepatitis B virus (HBV) infection.