The role of HBsAg quantification for monitoring natural history and treatment outcome

Abstract

Since its discovery by Blumberg in 1965, the hepatitis B virus antigen (HBsAg) is used as the fingerprint of hepatitis B infection. The HBsAg level is a reflection of the transcriptional activity of cccDNA. It is an important marker that not only indicates active hepatitis B infection but can also predict clinical and treatment outcomes. Assays for HBsAg quantification are fully automated and have high output. HBsAg titres are higher in HBe antigen (HBeAg)(+) than in HBeAg(À) patients and are negatively correlated with liver fibrosis in HBeAg(+) patients. In HBeAg(À) chronic hepatitis B, an HBsAg level <1000 IU/ml and an HBV DNA titre <2000 IU/ml accurately identify inactive carriers. During PEG-IFN treatment, HBsAg quantification is used to identify patients who will not benefit from therapy as early as week 12 on therapy, so that treatment may be stopped or switched-'week 12 stopping rule'. With nucleos(t)ide analogues (NA), the role of HBsAg quantification must be clarified. Several studies show that baseline and on-treatment HBsAg levels might identify patients that can be treated with no subsequent risk of reactivation. In clinical practice, HBsAg quantification is a simple and reproducible tool that can be used in association with HBV DNA to classify patients during the natural history of HBV and to monitor therapy.

Hepatitis B surface antigen loss and sustained viral suppression in Asian chronic hepatitis B patients: A community‐based real‐world study

“…It is possible that differences may result from differences in underlying genotype, but that is less likely given that the country of origin and thus likely genotype of our cohort is similar to those previously described. Another possibility is that baseline quantitative HBsAg levels were lower in our cohort compared to previous studies, which may have translated into higher rates of achieving HBsAg loss . However, data regarding quantitative HBsAg levels in our cohort were not available for analysis, and we have no reason to suspect that our patients would have had significantly lower levels.…”

Combination of DNA Prime – Adenovirus Boost Immunization with Entecavir Elicits Sustained Control of Chronic Hepatitis B in the Woodchuck Model

“…Some studies in chronically HBV-infected patients suggest that a low baseline HBsAg levels are associated with control of replication post therapy with nucleos(t)ide analogues [45], [46]. However, no information about the influence of HBsAg levels on the effects of immunotherapeutic approaches is available in patients yet.…”

Viral Hepatitis B: Clinical and Epidemiological Characteristics

“…Current assays for measuring HBsAg levels capture all forms of HBsAg, including virion-associated HBsAg and subviral particles. HBsAg levels may reflect hepatocyte cccDNA level and/or cccDNA transcriptional activity, as well as integrated HBV sequence, and its clinical utility may relate to a semi-quantitative measure of overall liver "HBV load" (Martinot-Peignoux et al 2013). Several studies of variation in HBsAg levels during the natural history of hepatitis B have shown that HBsAg is highest during the immunotolerant phase and declines through the immune clearance and control phases (Fig.…”