Enhanced HBsAg synthesis correlates with increased severity of fibrosis in chronic hepatitis B patients.
OBJECTIVE
Little 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.


METHODS
Chronic 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.


RESULTS
A 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).


CONCLUSIONS
Although 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.
Department of Infectious Diseases, Chenggong Hospital affiliated to Xiamen University (The 174th Hospital of PLA), Xiamen, China.
Mei-Zhu
MZ
Hong
Department of Infectious Diseases, Chenggong Hospital affiliated to Xiamen University (The 174th Hospital of PLA), Xiamen, China.
Wen-Qi
WQ
Huang
Department of Infectious Diseases, Chenggong Hospital affiliated to Xiamen University (The 174th Hospital of PLA), Xiamen, China.
Feng
F
Min
Department of Infectious Diseases, Chenggong Hospital affiliated to Xiamen University (The 174th Hospital of PLA), Xiamen, China.
Jin-Chao
JC
Xu
Department of Pathology, Chenggong Hospital affiliated with Xiamen University (The 174th Hospital of PLA), Xiamen, China.
Zhen
Z
Lin
Department of Statistics, School of Economics, Xiamen University, Xiamen, China.
Kuang-Nan
KN
Fang
Department of Gastroenterology, Zhongshan Hospital affiliated with Xiamen University, Xiamen, China.
Jin-Shui
JS
Pan
D000328:Adult; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D055815:Young Adult
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens