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Journal of Clinical Microbiology, December 2003, p. 5449-5455, Vol. 41, No. 12
0095-1137/03/$08.00+0     DOI: 10.1128/JCM.41.12.5449-5455.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

High Prevalence of Hepatitis B Virus Pre-S Mutant in Countries Where It Is Endemic and Its Relationship with Genotype and Chronicity

Tran Thien-Tuan Huy,1,2,3 Hiroshi Ushijima,2 Khin Maung Win,4 Pairoj Luengrojanakul,5 Pradeep Krishna Shrestha,6 Zhao-Hua Zhong,7 Andrei V. Smirnov,8 Teresa Casanovas Taltavull,9 Tetsutaro Sata,1 and Kenji Abe1*

Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan,1 Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, Tokyo, Japan,2 Department of Gastroentero-Hepatology, Cho Ray Hospital, Ho Chi Minh City, Vietnam,3 Department of Hepatology, Yangon General Hospital, Yangon, Myanmar,4 Division of Gastroenterology, Mahidol University Siriraj Hospital, Bangkok, Thailand,5 Department of Gastroenterology, Tribhuvan University Teaching Hospital, Katmandu, Nepal,6 Department of Microbiology, Harbin Medical University, Harbin, China,7 Department of Children's Infectious Diseases, Russian State Medical University, Moscow, Russia,8 Liver and Kidney Transplant Unit, Hospital of Bellvitge, Barcelona, Spain9

Received 18 May 2003/ Returned for modification 15 July 2003/ Accepted 20 September 2003

It has been reported that hepatitis B virus (HBV) mutants carrying mutations in the pre-S region can be found in infected patients. In this study, we investigated the prevalence of the HBV variant with the pre-S mutant in different geographic regions, including countries with low and high levels of endemic HBV infection, and analyzed the correlation with clinical findings. We examined 387 HBV DNA-positive serum samples from individuals among 12 countries, consisting of Vietnam, Myanmar, Thailand, China, Korea, Nepal, Japan, Russia, Spain, United States, Bolivia, and Ghana. HBV pre-S mutants were detected in 71 (18.3%) of 387 serum samples tested. This mutant was the most prevalent in Vietnam (36%), followed by Nepal (27.3%), Myanmar (23.3%), China (22.4%), Korea (14.3%), Thailand (10.5%), Japan (7.7%), and Ghana (4.3%). In contrast, no case with this mutation was found in Russia, Spain, United States, and Bolivia. Among the HBV deletion mutations, 15.5% (11 of 71) occurred in the pre-S1 and 46.5% (33 of 71) in the pre-S2 regions. Eight (11.3%) cases had a mutation in both the pre-S1 and pre-S2 regions. In addition, a point mutation at the pre-S2 starting codon was observed in 19 (26.7%) cases. The detection rate of the HBV mutant in patients with hepatocellular carcinoma was significantly higher than in other patients (P < 0.05). Furthermore, these mutants were found more frequently in genotype B (25%) and genotype C (24.5%) than in the other genotypes (P < 0.05). Our results indicated that there was a high prevalence of HBV pre-S mutation in regions of endemic HBV infection in Asia. Furthermore, the pre-S mutation appeared to be correlated with hepatocellular carcinoma and HBV genotypes.

* Corresponding author. Mailing address: Department of Pathology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: (81) 3-5285-1111, ext. 2624. Fax: (81) 3-5285-1189. E-mail: kenjiabe{at}nih.go.jp.

Journal of Clinical Microbiology, December 2003, p. 5449-5455, Vol. 41, No. 12
0095-1137/03/$08.00+0     DOI: 10.1128/JCM.41.12.5449-5455.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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