What is the role of serology for the study of chronic hepatitis B virus infection in the age of molecular biology?

Abstract

To assess quantitative serology in chronic hepatitis B virus (HBV) infection, testing by novel immunoassays has been carried out on 202 specimens from untreated patients and in 83 samples from 10 patients with chronic hepatitis B treated with lamivudine. Serum samples were assayed for quantitative HBsAg, in comparison with quantitative HBV-DNA, and for anti-HBc IgM and the avidity index (AI) of total anti-HBc antibodies. The AI was high (mean: 0.93 +/- 0.19) in all groups, confirming the consistency of this procedure in chronic HBV infections. A low-level positivity (2-28 Paul-Ehrlich units/ml) for IgM anti-HBc was detectable both in HBeAg-positive and in HBeAg-negative untreated chronic hepatitis cases (mean S/CO values by the Abbott Architect assay: 0.51 +/- 0.12 and 0.48 +/- 0.10, respectively; correlation between assays: r = 0.685), while treated patients (mean: 0.20 +/- 0.15) and inactive carriers (mean: 0.17 +/- 0.21), were generally negative for IgM. The levels of HBsAg (IU/ml) showed a weak correlation with HBV-DNA (IU/ml). A difference in HBsAg levels was found between inactive carriers (1,935 +/- 2,887 IU/ml) and chronic hepatitis B cases, either treated (5,199 +/- 9,259 IU/ml) or untreated (14,596 +/- 15,227 IU/ml). Pre-treatment levels of HBsAg in patients undergoing lamivudine treatment were correlated with a sustained response to therapy over 13-33 months (mean: 27.3) of follow-up: mean HBsAg values were 1,576 + 1,487 IU/ml in five responders and 6,063 + 5,142 in five nonresponders or breakthrough responders (P < 0.05). The availability of standardized quantitative immunoassays for HBsAg and anti-HBc IgM may be considered in addition to quantitative HBV-DNA in the staging and monitoring of chronic HBV infection.

Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B

“…Initially, HBsAg levels were expressed as serial dilutions of a reference sample from the Paul Ehrlich Institute (Langen, Germany) (44). Recently, new quantitative HBsAg assays have been developed that fulfill the prerequisites of a biomarker: reproducibility, automated quantification with high-throughput platforms, relatively low cost ( o 10% of the cost of a serum HBV DNA assay) and standardization (IU/ml) (45,46). Indeed, the most recent evidence supports the role of HBsAg as a predictive marker for an anti-HBV treatment response (47)(48)(49)(50)(51)(52)(53).…”

The role of quantitative hepatitis B serology in the natural history and management of chronic hepatitis B

“…In patients treated with lamivudine, pretreatment HBsAg titers have been correlated with sustained virologic response [73] and HBsAg seroconversion [51,74]. Rising HBsAg concentrations are associated with the emergence of lamivudine resistance [72].…”

Hepatitis B Virus DNA is Absent in Lebanese Blood Donors Who Are Positive for Both Anti-Hbc and Anti-Hbs Antibodies

“…Following HBV infection, antibody responses to different HBV proteins, including anti-HBc and anti-HBs, are detected in human sera (12). Following clearance of transient HBV infection, antiHBc level remains high for longer periods than other HBV markers, thus serving as a universal indicator for HBV infection (13). The "anti-HBc" serological status could be attributed to different parameters among which are: (a) passive transfer of anti-HBc; (b) a recent HBV infection during which HBsAg has disappeared, while anti-HBs levels are yet undetectable; or (c) chronic HBV infection during which HBsAg is undetectable due to very low viraemia, a clinical phase recognized as occult HBV infection (14)(15)(16)(17).…”