New insight in the pathobiology of hepatitis B virus infection

Abstract

Chronic hepatitis B virus (HBV) infection remains a major health burden and the main risk factor for the development of hepatocellular carcinoma worldwide. However, HBV is not directly cytopathic and liver injury appears to be mostly caused by repeated attempts of the host's immune responses to control the infection. Recent studies have shown that the unique replication strategy adopted by HBV enables it to survive within the infected hepatocyte while complex virus-host interplays ensure the virus is able to fulfil its replication requirements yet is still able to evade important host antiviral innate immune responses. Clearer understanding of the host and viral mechanisms affecting HBV replication and persistence is necessary to design more effective therapeutic strategies aimed at improving the management of patients with chronic HBV infection to eventually achieve viral eradication. This article focuses on summarising the current knowledge of factors influencing the course of HBV infection, giving emphasis on the use of novel assays and quantitative serological and intrahepatic biomarkers as tools for predicting treatment response and disease progression.

Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems

“…The establishment of two complementary HBV model systems represents an opportunity to tackle questions regarding major components of the viral entry process and viral life cycle, including host factors underlying establishment and persistence of a nuclear cccDNA pool, the key viral reservoir that leaves patients susceptible to viral reactivation (29).…”

In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection

“…HBV has a small (3.2 kb), partially double-stranded genome and replicates through reverse transcription of pregenomic RNA (pgRNA). The covalently closed circular DNA (cccDNA) in the nucleus, which serves as the template for transcription of pgRNA and other subgenomic RNAs, is initially formed immediately after HBV entry and persists inside the host cells (2). cccDNA is notoriously refractory to the nucleos(t)ide analogs (NAs) commonly used in clinical practice that inhibit the reverse transcriptase activity of HBV polymerase (3,4).…”

Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B

“…Individuals infected during infancy represent the group that harbors the majority of the global reservoir of HBV and exert the greatest healthcare impact. A strong, diverse, adaptive immune response is considered essential for HBV clearance, but the mechanisms by which an individual orchestrates a favorable response are just beginning to be understood (5)(6)(7)(8).…”