Abstract
Background and AimsLittle is known about whether low serum HBsAg levels result from impaired HBsAg synthesis or a reduced number of hepatocytes caused by advanced liver fibrosis. Therefore, we investigated the capacity for HBsAg synthesis in a cross-sectional cohort of treatment-naïve chronic hepatitis B patients.MethodsChronic hepatitis B patients (n = 362) were enrolled; liver biopsies were performed and liver histology was scored, and serum HBsAg and HBV DNA levels were investigated. In the enrolled patients, 183 out of 362 have quantitative serum HBsAg levels. Tissue HBsAg was determined by immunohistochemistry.ResultsA positive correlation between serum HBsAg and HBV DNA levels was revealed in HBeAg(+) patients (r = 0.2613, p = 0.0050). In HBeAg(+) patients, serum HBsAg and severity of fibrosis were inversely correlated (p = 0.0094), whereas tissue HBsAg levels correlated positively with the stage of fibrosis (p = 0.0280). After applying the mean aminopyrine breath test as a correction factor, adjusted serum HBsAg showed a strong positive correlation with fibrosis severity in HBeAg(+) patients (r = 0.5655, p<0.0001). The adjusted serum HBsAg values predicted ‘moderate to severe’ fibrosis with nearly perfect performance in both HBeAg(+) patients (area under the curve: 0.994, 95% CI: 0.983–1.000) and HBeAg(−) patients (area under the curve: 1.000, 95% CI: 1.000–1.000).ConclusionsAlthough serum HBsAg levels were negatively correlated with fibrosis severity in HBeAg(+) patients, aminopyrine breath test-adjusted serum HBsAg and tissue HBsAg, two indices that are unaffected by the number of residual hepatocytes, were positively correlated with fibrosis severity. Furthermore, adjusted serum HBsAg has an accurate prediction capability.
Highlights
Chronic hepatitis B (CHB) remains one of the most common infectious diseases worldwide, and in Asia and Africa in particular
There is a positive correlation between hepatitis B virus (HBV) DNA level and liver cirrhosis and hepatocellular carcinoma (HCC) [1,2]
hepatitis B surface antigen (HBsAg) seroclearance confers a favorable prognosis in cirrhosis and HCC [3,4,5,6]
Summary
Chronic hepatitis B (CHB) remains one of the most common infectious diseases worldwide, and in Asia and Africa in particular. A marked decline in hepatitis B virus (HBV) DNA load and/or quantified serum hepatitis B surface antigen (HBsAg) can be observed. There is a positive correlation between HBV DNA level and liver cirrhosis and hepatocellular carcinoma (HCC) [1,2]. In the past several years, the role of quantified serum HBsAg in the surveillance of treatment efficacy has attracted interest. The risk of hepatocellular tumorigenesis is lower in the patients with clearance of serum HBsAg after interferon a-based antiviral therapy [7]. High levels of HBsAg increase the risk of HCC and vice versa [8]. We investigated the capacity for HBsAg synthesis in a cross-sectional cohort of treatment-naıve chronic hepatitis B patients
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