Current and future antiviral drug therapies of hepatitis B chronic infection

Despite significant improvement in the management of chronic hepatitis B virus(HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon(IFN)-α and monotherapy with five nucleos(t)ide analogues(NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection.

Role natural killer group 2D-ligand interactions in hepatitis B infection

Hepatitis B virus （HBV） infection is the leading causeof liver disease and hepatocellular carcinoma （HCC）worldwide, in spite of prophylactic vaccination andantiviral treatment modalities. The immunopathogenesisof HBV infection has been intensively studied and ispropelled by complex interactions between the virus andthe host immune system. Natural killer group 2D （NKG2D）is a well-characterized activating receptor, expressed onnatural killer （NK） cells, NK T cells and CD8＋ cytotoxic Tcells. This receptor is present in both humans and miceand binds to a diverge family of ligands that resemble theMHC-class Ⅰ molecules. Increasing evidence shows thatNKG2D-ligand interactions are critical in the establishmentof HBV persistence and the development of liver injuryand HCC. The expression of NKG2D ligands dependson the presence of several polymorphisms and is alsomodulated post-transcriptionally by HBV. While it isknown that HBV circumvents host’s innate immunityvia the NKG2D pathway but the exact mechanismsinvolved are still elusive. This letter discusses previousaccomplishments on the role of NKG2D ligand regulationin the development of chronic HBV, liver injury and HCC.Key words： Hepatitis B virus; Natural killer group 2Dreceptor; Natural killer cells; MHC class I polypeptiderelatedchain A; Hepatocellular carcinoma

Dietary factors can protect against liver cancer development

Liver cancer is the third leading cause of cancer mortality worldwide with hepatocellular carcinoma(HCC) representing more than 90% of primary liver cancers. Most HCC patients are also suffering from chronic liver disease(CLD). Evidence is emerging that the compositionof diet plays an important role in HCC and CLD development and may also have a chemoprotective role. In contrast to other types of cancer, there are few studies investigating the role of diet in hepatocarcinogenesis. From the available data it is evident that high intakes of red meat and dietary sugar positively correlate with HCC occurrence. On the contrary, high consumption of white meat, fish, vegetables, fruits and cereals are inversely associated with HCC risk. This letter discusses the potential role of dietary interventions in the prevention of hepatocarcinogenesis. The increasing HCC incidence and its high fatality are making HCC prevention an urgent matter. Dietary modifications are found to offer protection against HCC, however, new studies from well-designed and large prospective trials are required to confirm these results.

Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg^(+)/HBeAg^(-) mothers

Vertically transmitted hepatitis B virus(HBV)usually causes chronic infection.While combined active–passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive(HBsAg1)mothers at birth prevents vertical transmission,it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen(HBeAg).This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg1/HBeAg2 mothers.Blood was collected from 46 HBsAg1 mothers and their neonates(subjects)as well as 24 age-matched controls.All neonates of HBsAg1 mothers received appropriate immunoprophylaxis,and HBsAg and hepatitis B surface antibody(anti-HBs)antibody titers were determined after completion of the vaccination course.Peripheral blood mononuclear cells(PBMCs)from infants at birth,1 and 6 months of age were stimulated with recombinant HBsAg,hepatitis B core antigen(HBcAg)and mitogen,and interferon(IFN)-c concentrations were determined by ELISA.HBsAg-induced production of IL-2,IL-5,IL-6 and IL-10 was assessed using a cytometric bead array kit on cells from 6-month-old neonates post-vaccination.All neonates were HBsAg2 and responded to vaccination.Increased IFN-c production following HBcAg stimulation was seen in 30.4%of neonates born to HBsAg1/HBeAg2 mothers.Subjects demonstrated significantly higher IL-2 production post-HBsAg stimulation,whereas IL-5,IL-6 and IL-10 cytokine responses were not significantly different.Almost one-third of uninfected neonates developed viral antigen-induced IFN-c production,suggesting that they had been exposed to virions or viral derivatives.This encounter,however,did not impair their T-cell responses to vaccination.