Background & Aims: Little is currently known about whether low serum HBsAg should be due to impaired HBsAg synthesizing or diminished quantity of hepatocytes caused by advanced liver fibrosis. Therefore, we investigated the capability of HBsAg synthesizing in a cross-sectional cohort of treatment -naïve chronic hepatitis B patients. Methods: 362 chronic hepatitis B patients were enrolled in the present research. Liver biopsies were performed. Serum HBsAg and HBV DNA were investigated and liver histology was scored. Tissue HBsAg was determined by immunohistochemistry. Results: Positive correlation between serum HBsAg and HBV DNA levels was revealed in HBeAg(+) patients (r = 0.2613, p = 0.0050). In HBeAg(+) patients, inverse association was observed between serum HBsAg and fibrosis severity (p = 0.0094) whereas tissue HBsAg has a positive relationship with fibrosis stage (p = 0.0280). After the induction of mean aminopyrine breath test as a correction factor, adjusted serum HBsAg showed a strong positive correlation with fibrosis severity in HBeAg(+) (r = 0.5655, p < 0.0001) patients. Adjusted serum HBsAg had a nearly perfect AUC of predicting ‘moderate to severe’ fibrosis in both HBeAg(+) patients (AUC: 0.994, 95% CI: 0.983 - 1.000) and HBeAg(-) patients (AUC: 1.000, 95% CI: 1.000 - 1.000). Conclusions: Though serum HBsAg levels have a negative association with fibrosis severity in HBeAg(+) patients, aminopyrine breath test-adjusted serum HBsAg and tissue HBsAg, two indices that are inflexible to various quantity of residual hepatocytes, have a positive correlation with fibrosis severity. Furthermore, adjusted serum HBsAg has an accurate prediction capability.
Keywords: Hepatitis B, Chronic; Hepatitis B Surface Antigens; Hepatitis B e Antigens; Immunohistochemistry; Liver fibrosis; Aminopyrine breath test.
Abbreviations: CHB, Chronic hepatitis B; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; ABT, aminopyrine breath test; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve; CI, confidence interval.
Chronic hepatitis B (CHB) remains one of the most common infectious diseases worldwide, especially in Asia and Africa. Interferon (or pegylated-interferon) and nucleosides (or nucleotide analogue) are prescribed widely for the treatment of CHB. Following effective therapy, dramatic decline of hepatitis B virus (HBV) DNA load and/or quantified serum hepatitis B surface antigen (HBsAg) could be observed. Positive correlation between HBV DNA level and liver cirrhosis or hepatocellular carcinoma (HCC) has been elucidated [1, 2]. In the past several years, special interest has risen up in the role of quantified serum HBsAg in surveillance on treatment efficacy. HBsAg seroclearance confers to favorable prognosis regarding cirrhosis and HCC [3-6]. Patients with clearance of serum HBsAg related to interferon α based antiviral therapy have lower risk of liver cancer...