Prevalence of Hbv Precore/Core Promoter Variants in the... : Hepatology (original) (raw)

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Chu, Chi-Jen1; Keeffe, Emmet B.2; Han, Steven-Huy3; Perrillo, Robert P.4; Min, Albert D.5; Soldevila-Pico, Consuelo6; Carey, William7; Brown, Robert S. Jr.8; Luketic, Velimir A.9; Terrault, Norah10; Lok, Anna S.F. M.D.*,1

1_Division of Gastroenterology, University of Michigan, Ann Arbor, MI_

2_Stanford University, Stanford, CA_

3_University of California, Los Angeles, Los Angeles, CA_

4_Ochsner Clinic, New York, NY_

5_Mount Sinai School of Medicine, New York, NY_

6_University of Florida, Gainesville, FL_

7_Cleveland Clinic, Cleveland, OH_

8_Columbia–Presbyterian Medical Center, New York, NY_

9_Virginia Commonwealth University, Richmond, VA_

10_University of California, San Francisco, San Francisco, CA_

* Division of Gastroenterology, University of Michigan Medical Center, 3912 Taubman Center, Box 0362, Ann Arbor, MI 48109–0362. fax: 734–936–7392; E-mail: [email protected].

Received: 26 February 2003; Accepted: 27 May 2003

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.”