Prevalence of HBV precore/core variants in US

OCD

HEPATOLOGY
September 2003 . Volume 38 . Number 3
Original Articles: Viral Hepatitis

Prevalence of HBV precore/core promoter variants in the United States

Chi-Jen Chu1 Emmet B. Keeffe2 ,Steven-Huy Han3
Robert P. Perrillo4 ,Albert D. Min5 ,Consuelo Soldevila-Pico6
William Carey7 ,Robert S. Brown Jr.8 Velimir A. Luketic9
Norah Terrault10 ,Anna S.F. Lok1
U.S. HBV Epidemiology Study Group

   Abstract
Variants in the precore (G1896A) and core promoter (A1762T, G1764A) regions
of hepatitis B virus (HBV) may be related to serum HBV DNA levels and
severity of liver disease. The aims of this nationwide study were to
determine the prevalence of HBV precore/core promoter variants in the United
States and the association between these variants and patient demographics,
HBV genotypes, serum HBV DNA level, and severity of liver disease. A total
of 694 consecutive chronic HBV-infected patients seen in 17 U.S. liver
centers during a 1-year period were enrolled. Demographic, clinical, and
laboratory data were collected. Sera were tested for HBV genotypes as well
as precore and core promoter variants by line-probe assays. Quantitative HBV
DNA levels were determined using Cobas Amplicor HBV Monitor kits. Precore
and core promoter variants were found in 27% and 44% of patients with
chronic HBV infection in the United States. Precore and core promoter
variants were more common in hepatitis B e antigen (HBeAg)-negative than in
HBeAg-positive patients (precore, 38% vs. 9%; core promoter, 51% vs. 36%;
respectively, P < .001). The prevalence of these variants was related to
ethnicity, place of birth, and HBV genotypes. Patients with core promoter
variants were more likely to have hepatic decompensation. Precore and/or
core promoter variants were associated with higher serum HBV DNA levels in
HBeAg-negative but not in HBeAg-positive patients. In conclusion, HBV
precore and core promoter variants are not rare in the United States.
Physicians should be aware of the existence of HBV precore and core promoter
variants and the clinical condition of "HBeAg-negative chronic hepatitis."
(HEPATOLOGY 2003;38:619-628.)

   Publishing and Reprint Information  From the 1Division of
Gastroenterology, University of Michigan, Ann Arbor, MI; 2Stanford
University, Stanford, CA; 3University of California, Los Angeles, Los
Angeles, CA; 4Ochsner Clinic; 5Mount Sinai School of Medicine, New York, NY;
6University of Florida, Gainesville, FL; 7Cleveland Clinic, Cleveland, OH;
8Columbia-Presbyterian Medical Center, New York, NY; 9Virginia Commonwealth
University, Richmond, VA; and 10University of California, San Francisco, San
Francisco, CA.
Received February 26, 2003.
Accepted May 27, 2003.
Innogenetics Inc. provided Inno-Lipa kits for HBV genotyping and detection
of precore stop codon and core promoter variants. Roche Diagnostic Systems
Inc. provided Cobas HBV Amplicor Monitor kits for quantitative HBV DNA
testing. No grant funding was provided by Innogenetics or Roche.
GlaxoSmithKline provided an unrestricted grant for collection and shipment
of samples. C.J.C. was supported by Taipei Veterans General Hospital and
Research Foundation of Digestive Medicine, Republic of China, E.B.K. was
supported by the Hutchison Program in Translational Medicine at Stanford
University, and A.S.F.L. was supported by National Institutes of Health
contract N01-DK-9-2323 and grants U01-DK-60344 and U01-DK-57577.
Address reprint requests to: Anna S. F. Lok, M.D., Division of
Gastroenterology, University of Michigan Medical Center, 3912 Taubman
Center, Box 0362, Ann Arbor, MI 48109-0362. E-mail: [email protected] ; fax:
734-936-7392.
Copyright &copy; 2003 by the American Association for the Study of Liver
Diseases.
0270-9139/03/3803-0012$30.00/0
doi:10.1053/jhep.2003.50352