Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma.
OBJECTIVE
The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk.


METHODS
This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers.


RESULTS
The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30-75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither.


CONCLUSIONS
Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.
The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Jessica
J
Liu
The Genomics Research Center, Academia Sinica, Taipei, Taiwan Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, Taiwan Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Hwai-I
HI
Yang
Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.
Mei-Hsuan
MH
Lee
Department of Gastroenterology, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan.
Sheng-Nan
SN
Lu
The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Chin-Lan
CL
Jen
Roche Diagnostics, Ltd, Basel, Switzerland.
Richard
R
Batrla-Utermann
MacKay College of Medicine, Taipei, Taiwan.
Li-Yu
LY
Wang
The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
San-Lin
SL
You
Graduate Institute of Epidemiology and Preventative Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Chuhsing K
CK
Hsiao
Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan.
Pei-Jer
PJ
Chen
The Genomics Research Center, Academia Sinica, Taipei, Taiwan Graduate Institute of Epidemiology and Preventative Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Chien-Jen
CJ
Chen
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006509:Hepatitis B / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D013624:Taiwan
D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens
HEPATITIS B; HEPATOCELLULAR CARCINOMA