Elsevier

Journal of Hepatology

Volume 52, Issue 4, April 2010, Pages 508-513
Journal of Hepatology

Research Article
Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: A perspective on Asia

https://doi.org/10.1016/j.jhep.2010.01.007Get rights and content

Background & Aims

Data from clinical trials suggest a potential role for on-treatment monitoring of serum HBsAg titres during interferon-alpha (pegIFN) therapy in predicting virological responses. However, baseline HBsAg titres during the natural history of chronic hepatitis B (CHB) have not been well-characterized. We aimed to define the serum HBsAg titres during the different phases of CHB in a cohort of Asian patients infected with either genotype B or C HBV.

Methods

Two-hundred and twenty patients were classified into immune-tolerant (IT), immune-clearance (IC), non/low-replicative (LR) or hepatitis B e antigen negative hepatitis (ENH) phases. Serum HBsAg was quantified using the ARCHITECT platform (Abbott Laboratories, Chicago, USA). Correlation of HBsAg titre with HBV DNA and serum ALT within each phase of infection was performed.

Results

Median HBsAg titres were different between each phase of CHB (p = 0.001): IT (4.53 log10 IU/ml), IC (4.03 log10 IU/ml), LR (2.86 log10 IU/ml), and ENH (3.35 log10 IU/ml). HBsAg titres were highest in the IT phase, and lowest in the LR phase. In general, median HBsAg titres were similar between genotypes B and C HBV. Serum HBsAg titres only correlated with HBV viral load in the IC phase. No correlation between the serum HBsAg level and ALT was observed.

Conclusions

This study demonstrated significant differences in median baseline serum HBsAg titres across the different phases of CHB. These results provide further insight into the HBV viral life cycle in the setting of the various phases of CHB. Baseline HBsAg quantification may help refine future treatment algorithms for both immune-modulator therapy and oral nucleos(t)ide analogue therapy.

Introduction

The natural history of chronic hepatitis B (CHB) is typically regarded as consisting of four phases [1], [2]; immune-tolerant (IT), immune-clearance (IC), non/low-replicative (LR), and hepatitis B e antigen negative hepatitis (ENH). These phases have been classified by specific biochemical, serological and virological characteristics, including serum ALT levels, hepatitis B e antigen (HBeAg) serostatus, and hepatitis B virus DNA (HBV DNA) titre. It is important to note that these phases do not occur in all individuals, and do not always necessarily occur sequentially [3].

The understanding of the pathogenesis and natural history of CHB continues to evolve. This has been facilitated by the improved sensitivity of HBV DNA viral load assays, and the development of assays for the detection and measurement of HBV intrahepatic replicating forms of the virus such as covalently closed circular DNA (cccDNA) and other replicative intermediates [4], [5]. Recently, sensitive and reliable assays have also been developed to quantify both serum hepatitis B surface antigen (HBsAg) and HBeAg.

HBsAg seroclearance represents the preferred endpoint of therapy for CHB, as it is believed to represent successful immunological control of active HBV replication. Recent data from clinical trials suggest a potential role for on-treatment monitoring of serum HBsAg and HBeAg titres during interferon-alpha (pegIFN) therapy in predicting virological responses [6], [7]. However, baseline HBsAg titres have not been well-characterized in each phase of CHB, particularly in the IT and LR phases. The main objective of this study was to determine the serum HBsAg titres during the different phases of the natural history of CHB in a cohort of Asian patients infected with genotype B or C HBV.

Section snippets

Patients

A cross-sectional study was performed in patients with CHB from two tertiary hospitals (St. Vincent’s Hospital Melbourne and Liverpool Hospital Sydney, Australia). Patients included from Liverpool hospital were a cohort of pregnant women. Only patients with genotype B or C HBV infection were included. All patients tested negative for markers of hepatitis C virus, hepatitis D virus, and human immunodeficiency virus (HIV). Markers for co-existent auto-immune or metabolic liver disease were

Results

Two-hundred and twenty treatment naïve patients were recruited. Patients from Liverpool Hospital, Sydney comprised a cohort of pregnant women (n = 70). The classification of patients into respective phases of CHB were: IT (n = 32), IC (n = 55), LR (n = 50), ENH (n = 83).

The baseline patient characteristics are presented in Table 1. All patients were of Asian ethnicity and were infected with either genotype B or C HBV. There were overall more females in the study group (56%). HBeAg positive patients were

Discussion

This study aimed to evaluate the baseline serum HBsAg titres in different phases of CHB infection. All patients were treatment naïve and chronically infected with either genotype B or C HBV, and were of Asian ethnicity. This study demonstrates that serum HBsAg titres differ between the four phases of CHB. This finding was also clearly demonstrated in an accompanying article by Jaroszewicz et al., which examined HBsAg levels in a predominantly European cohort (HBV genotypes A and D). In our

Acknowledgements

The authors who have taken part in this study declared that they do not have anything to declare regarding funding from industry or conflict of interest with respect to this manuscript. This work was supported by a Postgraduate Scholarship from the Gastroenterological Society of Australia (GESA). SL has been in receipt of a consultancy for Abbott Diagnostics Division. Abbott Diagnostics (Abbott Laboratories, Chicago, USA) provided the Architect Instrument for quantitative serological testing.

References (24)

  • M.R. Brunetto et al.

    Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B

    Hepatology

    (2009)
  • R. Moucari et al.

    Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients

    Hepatology

    (2009)
  • Cited by (310)

    • Interpretation of HBV Serologies

      2021, Clinics in Liver Disease
    • Combination of quantitative hepatitis B core antibody (qHBcAb) and aspartate aminotransferase (AST) can accurately diagnose immune tolerance of chronic hepatitis B virus infection based on liver biopsy

      2021, Clinics and Research in Hepatology and Gastroenterology
      Citation Excerpt :

      Owing to the invasiveness of liver biopsy, which is not accepted by most patients, there is an urgent need for other effective non-invasive indicators to replace liver biopsy as a predictor of immune tolerance. In the past ten years, there have been a lot of studies on the quantitative analysis of non-invasive markers in the natural history of hepatitis B. Two recent studies [11,12] have shown the role of HBsAg quantification in hepatitis B immune tolerance, suggesting that the titer of HBsAg quantification during immune tolerance period is higher, but unfortunately neither is histological evidence for its definition of immune tolerance, only peripheral blood indicator. However, a large number of recent studies have shown that among people with HBeAg positive, high hepatitis B virus load and normal ALT, 5%–49.4% of liver inflammation or fibrosis were reported in different studies [13–19].

    • Inter-method variability of hepatitis B surface antigen quantification in a cohort of Egyptian patients with chronic hepatitis B virus

      2021, Arab Journal of Gastroenterology
      Citation Excerpt :

      Our results demonstrated a significant correlation between HBsAg levels and HBV viral load for the Architect™ assay (r = 0.61, p < 0.001) and for the Elecsys® assay (r = 0.75, p < 0.001) in the immune phases of chronic HBV infection. A similar correlation was reported by Cheng et al. (2014) [6] who used both assays, whereas Nguyen et al. (2010) [25], Zeng et al. (2014) [7], Karra et al. (2016) [26], and Cheng (2018) [27] used the Architect™ assay only. Although Karagoz et al. (2016) [14] found a significant correlation between the Elecsys® and Architect™ assays, qHBsAg measured by the Architect™ assay, but not by the Elecsys® assay, was significantly correlated with HBV-DNA levels.

    View all citing articles on Scopus
    View full text