Article Text

Download PDFPDF
Original article
Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma
  1. Jessica Liu1,
  2. Hwai-I Yang1,2,3,
  3. Mei-Hsuan Lee4,
  4. Sheng-Nan Lu5,
  5. Chin-Lan Jen1,
  6. Richard Batrla-Utermann6,
  7. Li-Yu Wang7,
  8. San-Lin You1,
  9. Chuhsing K Hsiao8,
  10. Pei-Jer Chen9,10,
  11. Chien-Jen Chen1,8
  12. for the R.E.V.E.A.L.-HBV Study Group
  1. 1The Genomics Research Center, Academia Sinica, Taipei, Taiwan
  2. 2Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, Taiwan
  3. 3Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
  4. 4Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan
  5. 5Department of Gastroenterology, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
  6. 6Roche Diagnostics, Ltd, Basel, Switzerland
  7. 7MacKay College of Medicine, Taipei, Taiwan
  8. 8Graduate Institute of Epidemiology and Preventative Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
  9. 9Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  10. 10Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
  1. Correspondence to Professor Chien-Jen Chen, the Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan; chencj{at}


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.


Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles