Natural History of Chronic Hepatitis B REVEALed

February 18, 2011

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06695.x/abstract

Chien-Jen Chen1,*, Hwai-I Yang2DOI: 10.1111/j.1440-1746.2011.06695.x

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Accepted Article (Accepted, unedited articles published online for future

issues)

Author Information

1Genomics Research Center, Academia Sinica, Taipei, and Graduate Institute of

Epidemiology, College of Public Health, National Taiwan University, Taipei,

Taiwan.

2Molecular and Genomic Epidemiology Center, China Medical University Hospital ,

Taichung, Taiwan.

*Correspondence: Chien-Jen Chen,

*Correspondence: Chien-Jen Chen, ScD, Genomics Research Center, Academia Sinica.

128 Academia Road Section 2, Nankang, Taipei 115, Taiwan (cjchen@...);

Telephone: +886-2-27871270; FAX: +886-2-27898784.

The R.E.V.E.A.L.-HBV Study was supported by grants from the Academia Sinica,

National Health Research Institutes, and Bristol-Myers Squibb Co., USA.

This is an Accepted Article that has been peer-reviewed and approved for

publication in the Journal of Gastroenterology and Hepatology, but has yet to

undergo copy-editing and proof correction. Please cite this article as an

" Accepted Article " ; doi: 10.1111/j.1440-1746.2011.06695.x

The R.E.V.E.A.L.-HBV Study was supported by grants from the Academia Sinica,

National Health Research Institutes, and Bristol-Myers Squibb Co., USA.

This is an Accepted Article that has been peer-reviewed and approved for

publication in the Journal of Gastroenterology and Hepatology, but has yet to

undergo copy-editing and proof correction. Please cite this article as an

" Accepted Article " ; doi: 10.1111/j.1440-1746.2011.06695.x

Publication History

Accepted manuscript online: 16 FEB 2011 05:07AM EST

Received: 02/07/2011 , Accepted: 02/09/2011

Abstract

Chronic hepatitis B is a worldwide public health challenge. Knowledge of natural

history of chronic hepatitis B is important for the management of the disease. A

community-based prospective cohort study was carried out to evaluate the risk

predictors of progression of chronic hepatitis B in Taiwan. A total of 23,820

participants were enrolled in 1991-1992 from seven townships in Taiwan. Their

serum samples were collected at study entry and tested for hepatitis B surface

antigen (HBsAg) and e antigen (HBeAg), antibodies against hepatitis C virus

(anti-HCV), alanine aminotransferase (ALT), and á-fetoprotein (AFP). A subcohort

of 3,653 male and female participants who were seropositive for HBsAg and

seronegative for anti-HCV was included in the R.E.V.E.A.L.-HBV study. Newly

developed cases of cirrhosis and hepatocellular carcinoma (HCC) were ascertained

through follow-up examination and data linkage with profiles of National Cancer

Registry, National Health Insurance Database and Death Certification System.

The incidence of both HCC and cirrhosis were significantly associated with serum

HBV DNA levels in a dose-response relationship from <300 (undetectable) to >106

copies/mL. The biological gradients remained significant (P < 0.001) after

adjustment for age, sex, habits of cigarette smoking and alcohol drinking, HBeAg

serostatus, and serum ALT level at cohort entry. A significant association with

risk of cirrhosis and HCC was also observed for HBV genotype, precore G1896A

mutant and basal core promoter A1762T/G1764A double mutant. Nomograms have been

developed for the long-term risk prediction of cirrhosis and HCC for patients

with chronic hepatitis B. Inactive carriers of HBV have an increased HCC

incidence and liver-related mortality than HBsAg-seronegative controls. Serum

HBV DNA level at study entry is a major predictor of spontaneous seroclearance

of HBeAg, HBV DNA and HBsAg.These findings may inform the effective and

efficient management of chronic hepatitis B.

February 18, 2011