High levels of serum hepatitis B virus DNA in patients with ‘anti-HBc alone’: role of HBsAg mutants

Abstract

It remains unclear how the detection of hepatitis B core antibody (anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) should be interpreted and whether all patients with this pattern need to be tested for hepatitis B virus (HBV)-DNA. This study aimed at reassessing the significance of 'anti-HBc alone' in unselected sera referred to the clinical laboratory and determining whether significant HBV viraemia can be found in this setting. Of the 6431 patients tested for HBsAg, total anti-HBc and anti-HBs in a Paris hospital over a 1-year period, 362 (5.6%) had 'anti-HBc alone' (24.8% of anti-HBc-positive patients). Only 11 of the 362 sera (3.0%) were found to be false positive. One patient was in the resolving phase of acute hepatitis B. HBV-DNA was detected in 10 of 362 (2.8%) patients, using a commercial standardized assay (threshold: 350 IU/mL). Viral loads exceeded 10(4) copies/mL in 6 of 10 patients. Mutations in the HBsAg immunodominant region were identified in seven of the viraemic patients. HBsAg was detected in only two cases when retested by one of the latest, multivalent assays. Neither human immunodeficiency virus nor hepatitis C virus serostatus distinguished between patients with and without HBV-DNA. In conclusion, 'anti-HBc alone' should be considered a risk marker for a so-called 'false occult' HBV infection with significant viraemia. Indeed, results in this hospital population indicate that a small proportion of patients with 'anti-HBc alone' have high viral loads, revealing the occurrence of infection with HBV mutants that escape detection even by multivalent HBsAg assays.

Management of the HBV reactivation in isolated HBcAb positive patients affected with Non Hodgkin Lymphoma

“…It has to be noticed that this prevalence is similar to the supposed prevalence of OBI infection in blood donors in the same area [29-44]. This finding may confirm the general conviction that onco-haematological patients are at high risk of HBV reactivation if they are OBI carriers.…”

Responses to hepatitis B vaccine in isolated anti-HBc positive adults

“…[1][2][3] Another possibility is that anti-HBc findings represented false positive results or resulted from interactive antibody, and that such individuals had never been exposed to HBV. 4 The prevalence of these cases can range from 0.1% to 32% in various surveys, [5][6][7][8][9][10][11][12] depending upon the prevalence of HBV infection and patients investigated.…”

False-Negative Hepatitis B Virus (HBV) Surface Antigen in a Vaccinated Dialysis Patient with a High Level of HBV DNA in the United States

“…In this patient, the HBsAg was not detected by the Advia Centaur assay or the Diasorin kit but was identified with the Abbott AxSYM assay, which has been noted to better detect these HBV mutants (11). However, this assay does not capture all mutants, and even multivalent HBsAg assays miss some of these mutant strains (12). The accurate detection of HBV is critical since patients with these "false" occult HBV infections could potentially be offered antiviral therapy and should undergo routine surveillance for the development of hepatocellular carcinoma and cirrhosis.…”