Occult hepatitis B virus infection

doi:10.1016/j.jhep.2006.10.007

Journal of Hepatology

Volume 46, Issue 1, January 2007, Pages 160-170

https://doi.org/10.1016/j.jhep.2006.10.007 Get rights and content

Abstract

The persistence of hepatitis B virus (HBV) genomes in HBV surface antigen (HBsAg) negative individuals is termed occult HBV infection. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays, but more frequently it is due to a strong suppression of viral replication and gene expression. Occult HBV infection is an entity with world-wide diffusion, although the available data of prevalence in various categories of individuals are often contrasting because of the different sensitivity and specificity of the methods used for its detection in many studies. Occult HBV may impact in several different clinical contexts, including the transmission of the infection by blood transfusion or organ transplantation and its acute reactivation when an immunosuppressive status occurs. Moreover, much evidence suggests that it can favour the progression of liver fibrosis and above all the development of hepatocellular carcinoma.

Introduction

Occult hepatitis B virus infection (HBV) can be defined as the long-lasting persistence of viral genomes in the liver tissue (and in some cases also in the serum) of individuals negative for the HBV surface antigen (HBsAg). Suspected to exist since the early ’80s, this peculiar form of chronic viral infection has been better identified during the past ten years, when the availability of highly sensitive molecular biology techniques made it possible to disclose several of its virological aspects, to show its worldwide diffusion and to reveal its possible implication in various clinical contexts.

The aim of this review is to re-examine the available data about occult HBV infection, pointing out the aspects that most need to be clarified.

Section snippets

Virological aspects

The molecular basis of the occult infection is strictly related to the peculiar life cycle of the HBV, which is graphically summarized in Fig. 1. In particular, a fundamental step is the conversion of the ∼3 Kb relaxed circular genome into a covalently closed-circular DNA (cccDNA), a long lived HBV replicative intermediate that persists in the cell nuclei as a stable chromatinized episome and that serves as template for gene transcription [1], [2]. The stability and long-term persistence of

Clinical relevance

The emerging evidence of the potential, considerable clinical relevance of the occult HBV infection is the main reason for the growing interest in this topic. Occult HBV may impact in several different clinical contexts that we have schematically grouped into four main points which are briefly discussed below.

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