Occult hepatitis B virus infection: A hidden menace?

Abstract

Recovery from an acute hepatitis B virus (HBV) infection is associated with loss of HBV DNA from serum, hepatitis B e antigen seroconversion, hepatitis B surface antigen (HBsAg) seroconversion, and normalization of serum aminotransferases. These changes generally imply clearance of virus, but clinical observations have shown that reactivation of HBV infection can occur either spontaneously or after immunosuppression. [1][2][3] Recent studies showed that immune response to HBV remains vigorous long after an acute infection. In addition, HBV DNA can be detected by polymerase chain reaction (PCR) assays in serum, liver, and peripheral blood mononuclear cells more than a decade after an apparent recovery from HBV infection. [4][5][6] These findings suggest that recovery from acute hepatitis B may not result in complete virus elimination, but rather the immune system keeps the virus at very low levels. There is, however, no clear evidence that patients who have persistently low levels of HBV after recovery from acute hepatitis B develop progressive liver disease.The availability of PCR assays for HBV DNA allows the detection of 10 2 copies/mL compared with 10 6 copies/mL using hybridization assays. Using PCR assays, HBV DNA has been detected in some subjects who are HBsAg negative including those with no serologic markers of HBV infection. In this issue of the HEPATOLOGY, Bréchot et al. review the prevalence, virologic basis, and clinical significance of occult HBV infection. 7 For the clinician, several issues regarding occult HBV infection are pertinent: Does it exist? How common is it? What is the risk of transmission? What is the risk of progressive liver disease? How can it be diagnosed? Is antiviral therapy indicated? Before these issues can be addressed, it must be recognized that there is currently no standardized definition or diagnostic criteria of occult HBV infection. A simple definition would be the detection of HBV DNA in HBsAg-negative subjects. However, more specific information must be provided, as occult HBV infection is a heterogeneous clinical entity.Bréchot et al. provide very strong evidence that occult HBV infection exists and that most cases are related to very low levels of HBV rather than to HBV mutants that do not express or produce aberrant surface proteins and therefore are undetected by standard testing. 7 Because HBV-DNA detection is the key to diagnosis of occult HBV infection, the type of assay used and its sensitivity must be specified. The sensitivity of PCR assays for HBV DNA in studies on occult HBV infection varies from 10 1 to 10 3 copies/mL. 8 However, most PCR assays including commercially available assays are not standardized. 9 Other factors that may affect the detection rates of HBV DNA include the volume of sample used and the material tested. Thus, the limit of detection can be increased by using a larger volume of serum as in the case of the hybrid capture assay. Most studies on occult HBV infection have reported higher rates of HBV-DNA detection in liver or peripheral b...

Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers

“…HBV DNA levels in most of the individuals of this study with occult HBV infection was 10 2 -10 3 copies/ml, which is in accordance with the HBV DNA levels reported by Conjeevaram and Lok [2001] and well below the cut-off level proposed by NIH Workshop on HBV consensus 2000. Moreover, nested PCR is a cumbersome method and prone to contamination especially for cases with HBV DNA below 10 3 copies/ml.…”

Prevalence of Occult Hepatitis B Virus Infection in Hemodialysis Patients

“…3 Since HBV DNA level is usually less than 10 3 copies/mL in occult HBV infection, the detection of occult infection is strongly dependent on both the sensitivity and specificity of the assay. 15 Occult HBV infection is more frequently reported in the countries with high HBV infection, such as China, Japan and Taiwan, compared with Western countries. 6,11 South Korea is still an endemic area for HBV infection, and Kim et al 16 reported the prevalence of occult HBV infection was high (16%) in HBsAg negative subjects with normal serum ALT levels in Korea.…”

A study on sequence variations in pre‐S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non‐B, non‐C hepatocellular carcinoma patients in Taiwan

“…5 This so-called occult HBV infection has been identified by sensitive polymerase chain reaction (PCR) assays that detect low levels of HBV DNA in serum and/or liver tissue of HBsAg-negative subjects. [6][7][8] Since the early 1980s, several studies have reported the detection of HBV DNA in both tumorous and non-tumorous liver tissue of HBsAg-negative HCC patients. 9,10 However, whether occult HBV infection also contributes to the pathogenesis of HCC remains unclear.…”