Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

Abstract

The hepatitis B virus (HBV) represents a worldwide public health problem; the virus is present in one third of the global population. However, this rate may in fact be higher due to occult hepatitis B virus infection (OBI). This condition is characterized by the presence of the viral genome in the liver of individuals sero-negative for the virus surface antigen (HBsAg). The causes of the absence of HBsAg in serum are unknown, however, mutations have been identified that produce variants not recognized by current immunoassays. Epigenetic and immunological host mechanisms also appear to be involved in HBsAg suppression. Current evidence suggests that OBI maintains its carcinogenic potential, favoring the progression of fibrosis and cirrhosis of the liver. In common with open HBV infection, OBI can contribute to the establishment of hepatocellular carcinoma. Epidemiological data regarding the global prevalence of OBI vary due to the use of detection methods of different sensitivity and specificity. In Latin America, which is considered an area of low prevalence for HBV, diagnostic screening methods using gene amplification tests for confirmation of OBI are not conducted. This prevents determination of the actual prevalence of OBI, highlighting the need for the implementation of cutting edge technology in epidemiological surveillance systems.

The epidemiology of hepatitis B virus infection in women of reproductive age in highly endemic areas in China

“…The definitions we used in this study were (i) HBV infection—HBsAg‐positive and/or anti‐HBc‐positive individuals, representing those currently or ever infected, (ii) HBV prevalence—the proportion of the population meeting the HBV infection definition, (iii) occult hepatitis B virus infection (OBI)—HBsAg‐negative individuals with detectable HBV DNA, and (iv) HBV susceptible—individuals negative for HBsAg, anti‐HBs and anti‐HBc …”

Occult Hepatitis B Virus Infection: A Review Update

“…Even a reduction in the binding antibody to a range of S mutants derived from commonly selected lamivudine-resistant HBV mutants has been shown. The expressed proteins containing these mutations had an altered antigenicity and may have the potential to escape neutralization by anti-HBs antibody 18 .…”

“…These mutations may be associated with reduced expression and secretion of HBsAg and could affect pre-S2/S mRNA splicing. Other mutations found in the overlap region of the core gene promoter, influence the low replicative potential while variants in the Pre-Core/Core sequences reduce the efficiency of replication through the functional structure of the epsilon signal, which is essential for pre genomic encapsidation and initiation of HBV DNA synthesis 18 .…”

“…Hyper acetylation of histones bound to cccDNA has been associated with increased viral replication in cell culture. A mutant HBx of only one nucleotide has been associated with a rapid hypo acetylation of histones bound to cccDNA, thereby weakening the recruitment of the p300 transcriptional activator 18 .…”

“…This can be through alterations to the infectious agent itself (genomic mutations), through competition with other hepatotropic agents or through the host response to infection. This ultimately leads to zero detection of HBsAg in the serum of patients when tested with the currently available assays 18 .…”