Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma.
BACKGROUND AND AIMS
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.
['Liu|Jessica|J|', 'Yang|Hwai-I|HI|', 'Lee|Mei-Hsuan|MH|', 'Lu|Sheng-Nan|SN|', 'Jen|Chin-Lan|CL|', 'Batrla-Utermann|Richard|R|', 'Wang|Li-Yu|LY|', 'You|San-Lin|SL|', 'Hsiao|Chuhsing K|CK|', 'Chen|Pei-Jer|PJ|', 'Chen|Chien-Jen|CJ|', '|||']
D000328:Adult D000368:Aged D015415:Biomarkers D006528:Carcinoma, Hepatocellular D004279:DNA, Viral D005260:Female D006509:Hepatitis B D006514:Hepatitis B Surface Antigens D006513:Hepatitis B e Antigens D006801:Humans D008113:Liver Neoplasms D008297:Male D008875:Middle Aged D016016:Proportional Hazards Models D012307:Risk Factors D013624:Taiwan
HEPATITIS B HEPATOCELLULAR CARCINOMA