Hepatitis B virus overexpresses suppressor of cytokine signaling-3 (SOCS3) thereby contributing to severity of inflammation in the liver.

The mechanism by which hepatitis B virus (HBV) infection causes severe inflammatory liver diseases is multifactorial and related to interactions with cell signaling pathways and the ensuing inflammatory response. Activation of JAK/STAT/SOCS signaling is essential for the induction of cellular antiviral responses, contributes to apoptosis and is negatively regulated by SOCS proteins. Recent reports have shown that SOCS3 activation interferes with viral protein expression and treatment response and thereby plays a major role in hepatitis virus infections.

Dysregulation of hepatocyte cell cycle and cell viability by hepatitis B virus.

Background/aims: Dysregulation of the cell cycle is frequently associated with tumor development. Hepatitis B virus (HBV) is associated with a significant risk of developing hepatocellular carcinoma but the effects of HBV on cell cycle regulation are not completely understood.

Methods: We have used a recombinant adeno-HBV model system to investigate the effect of infection with HBV and the replication defective lamivudine resistant mutant rtM204I mutant on hepatocyte cell cycle and cell viability.

Subcellular mislocalization of mutant hepatitis B X proteins contributes to modulation of STAT/SOCS signaling in hepatocellular carcinoma.

Objective: The hepatitis B virus X (HBx) protein plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). One potential mechanism by which HBx can cause liver cancer may involve intracellular distribution and consecutively modulation of the proliferative important STAT/SOCS signaling with upregulation of STAT3.

Methods: 153 Vietnamese HBV-infected patients, including 48 patients with HCC, were analyzed.

Failure of lamivudine to reverse hepatitis B virus-associated changes in ERK, Akt and cell cycle regulatory proteins.

Background: Chronic infection with hepatitis B virus (HBV) is a major factor associated with the development of hepatocellular carcinoma, but the mechanism by which this occurs is unknown. Treatment of chronic hepatitis B with lamivudine results in virological suppression and histological improvement; however, the role of lamivudine in preventing the development of hepatocellular carcinoma is less well defined. We recently reported that replication of HBV in a cell-culture system was associated with the upregulation of pERK, pAkt, pc-Myc, nuclear cyclin B1, p21(cip1) and p53 together with G2 cell cycle arrest.

Modulation of MAPK pathways and cell cycle by replicating hepatitis B virus: factors contributing to hepatocarcinogenesis.

Background/aims: Chronic infection with the hepatitis B virus (HBV) is strongly associated with the development of hepatocellular carcinoma but the mechanism by which this occurs is unknown. Numerous studies have focused on the HBV X protein showing that it activates signal transduction pathways while few have investigated these changes in HBV-replicating hepatocytes.

Methods: We utilized the recombinant adenovirus system to deliver a replication competent HBV genome into Huh7 and primary marmoset hepatocytes (PMH) to examine the effects of active viral replication on the regulation of Ras-ERK signal transduction and related pathways.

Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam.

Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa.