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