New concepts in the immunopathogenesis of chronic hepatitis B: the importance of the innate immune response

Abstract

Acute and chronic infection with hepatitis B virus (HBV) is associated with an increased risk of developing liver disease including cirrhosis, decompensated liver disease, and hepatocellular carcinoma. The clinical presentation and natural history of HBV infection is mediated through complex interactions between the virus and the host immune response. HBV is not directly cytopathic to heptocytes; however, the interaction between the virus and the host immune response plays a central role in the pathogenesis of necroinflammation and liver fibrosis. Emerging data from immunopathogenesis studies in animal models and in vitro studies of liver biopsies from patients with chronic hepatitis B demonstrate a potentially important interaction between hepatitis B e antigen, HBV, and components of the innate immune response including Toll-like receptors, Kupffer cells, natural killer T-cells, and dendritic cells. These findings suggest that the innate immune response has an important role in influencing the outcome of acute and chronic HBV infection. The current knowledge regarding the interaction between HBV and components of the innate immune response during acute and chronic HBV infection is reviewed.

Cumulative viral evolutionary changes in chronic hepatitis B virus infection precedes hepatitis B e antigen seroconversion

“…Although innate immune responses appear mainly to be downregulated in chronic hepatitis B,18 innate immune mechanisms have already been shown to play an important role in pathogenesis of liver damage in chronic hepatitis B, particularly during hepatitis B flares,19 20 and in chronic hepatitis B necroinflammatory activity and liver cirrhosis 21. The mechanisms for these are still unclear.…”

Reversal of hepatitis B virus-induced immune tolerance by an immunostimulatory 3p-HBx-siRNAs in a retinoic acid inducible gene I-dependent manner

“…Whether HBV infection is cleared or persists as a progressive liver disease is determined by both viral and host factors. 1,2 It has been demonstrated that activation of pathogen recognition receptors (PRRs), including TLRs, RIG-I, and melanoma differentiationassociated gene 5 (MDA-5), can induce the inhibition of HBV replication via innate immune responses. 20 The local innate immune responses of the liver play major roles in inhibiting HBV replication, especially through the production of large amounts of antiviral cytokines (particularly type I IFN).…”

“…Whether HBV infection is cleared or persists as a progressive liver disease is determined by interaction between virus and host factors. 1,2 Although type I interferons (IFNs) can suppress HBV replication, the virus has the counteracting mechanisms to suppress the production and function of IFNs, leading to immune tolerance. For instance, HBV suppresses MxA expression at the promoter level or by inhibiting cellular proteasome activities in an HBV X gene (HBx)-dependent manner.…”

Hepatitis B e Antigen Seroconversion: A Critical Event in Chronic Hepatitis B Virus Infection

“…HBeAg seroconversion is typically preceded by hepatic flares characterized by increases in ALT levels, which signify an enhanced endogenous cellular T lymphocyte-mediated response against HBV [21]. Identifying the precise mechanisms involved in triggering immune response leading to HBeAg seroconversion is a focus of ongoing research [22,23].…”