Clinical Implications of HBsAg Quantification in Patients with Chronic Hepatitis B
Abstract
Quantification of serum hepatitis B surface antigen (HBsAg) helps the management of patients with chronic hepatitis B virus (HBV) infection. Median HBsAg levels differ significantly during the natural history of HBV infection, progressively declining from immune tolerance to inactive phase. The combination of an HBsAg <1000 IU/mL and HBV DNA <2000 IU/mL at a single time point accurately identifies true inactive carriers. During antiviral treatment, HBsAg levels decline more rapidly in patients under peg-interferon (Peg-IFN) than in those under nucleos(t)ide analogues (NUC), and in responders to peg-IFN compared to non responders suggesting that a response-guided therapy in both HBeAg-positive and -negative patients treated with Peg-IFN could improve to cost-effectiveness of this therapeutic approach. Given the low rates of HBsAg clearance on NUC therapy, new studies to test whether Peg-IFN and NUC combination fosters HBsAg decline in long-term responders to NUC, are being explored.
Serum hepatitis B surface antigen (HBsAg) is a reliable marker of overt hepatitis B virus (HBV) infection, whereas anti-HBs seroconversion represents the ultimate goal of antiviral therapy, that is, the closest outcome to cure infection.[1,2] Quantification of serum HBsAg has been recently standardized by automated quantitative assays leading to an increased interest in the clinical utilization of this marker.[3,4] HBsAg serum levels result from a balance between virus biology and a host's immune system as well as the indirect expression of transcriptionally active covalently closed circular DNA (cccDNA) rather than the product of the viral replication.[5] Several studies, particularly those with Peg-Interferon, have shown kinetics of HBsAg to predict a response to antiviral therapy, the predictive value of HBsAg being important for both treatment individualization[6–8] and interpretation of the phases of HBV infection in untreated patients.[9–11]
In this review we aim to analyze the recent findings on HBsAg quantification and its clinical use in the management of patients with chronic hepatitis B infection.
HBSAG QUANTIFICATION IN UNTREATED PATIENTS
Chronic HBV infection runs through four chronologic phases: an initial “immune tolerance phase” characterized by serum HBeAg and high viremia accompanied by null or minimal histologic damage. The second phase is the “immune clearance phase,” whereby the immune system recognizing HBV as a foreign invader causes extensive liver cell inflammation, that is, the HBeAg-positive chronic hepatitis. The third phase is the “inactive phase” in anti–HBe-positive patients showing persistently normal alanine aminotransferase (ALT) and low HBV DNA levels (<2000 IU/mL). The fourth phase is characterized by late reactivation of infection with persistently or intermittently increased HBV DNA and ALT levels accompanied by progressive liver damage, the so-called HBeAg-negative chronic hepatitis. While in most patients these phases occur in sequence, there are patients who apparently do not experience all phases like those persistently positive for HBeAg and those who remain persistently inactive carriers of HBsAg.