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©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Aug 28, 2009; 15(32): 4028-4036
Published online Aug 28, 2009. doi: 10.3748/wjg.15.4028
Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia
Andi Utama, Sigit Purwantomo, Marlinang Diarta Siburian, Rama Dhenni, Rino Alvani Gani, Irsan Hasan, Andri Sanityoso, Upik Anderiani Miskad, Fardah Akil, Irawan Yusuf, Wenny Astuti Achwan, Soewignjo Soemohardjo, Syafruddin AR Lelosutan, Ruswhandi Martamala, Benyamin Lukito, Unggul Budihusodo, Laurentius Adrianus Lesmana, Ali Sulaiman, Susan Tai
Andi Utama, Sigit Purwantomo, Marlinang Diarta Siburian, Rama Dhenni, Susan Tai, Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Lippo Karawaci, Tangerang, Banten 15810, Indonesia
Rino Alvani Gani, Irsan Hasan, Andri Sanityoso, Unggul Budihusodo, Laurentius Adrianus Lesmana, Ali Sulaiman, Hepatology Division, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia
Upik Anderiani Miskad, Fardah Akil, Irawan Yusuf, Center of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia
Wenny Astuti Achwan, Soewignjo Soemohardjo, Department of Internal Medicine, Mataram General Hospital, Mataram 83127, Indonesia
Syafruddin AR Lelosutan, Ruswhandi Martamala, Gastroentero-Hepatology Division, Department of Internal Medicine, Gatot Soebroto Hospital, Jakarta 10410, Indonesia
Benyamin Lukito, Department of Internal Medicine, Siloam Hospital Lippo Karawaci, Tangerang, Banten 15810, Indonesia
Author contributions: Utama A and Purwantomo S designed and performed the majority of experiments; Siburian MD and Dhenni R performed some experiments; Tai S was involved in experiment design and editing the manuscript; Gani RA, Hasan I, Sanityoso A, Miskad UA, Akil F, Yusuf I, Achwan WA, Soemohardjo S, Lelosutan SAR, Martamala R, Lukito B, Budihusodo U, Lesmana LA, and Sulaiman A coordinated and provided the collection of human materials and were involved in editing the manuscript.
Correspondence to: Andi Utama, PhD, Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Jalan Boulevard Jend, Sudirman 1688, Lippo Karawaci, Tangerang, Banten 15810, Indonesia.
autama@mrinstitute.org
Telephone: +62-21-54210123
Fax: +62-21-54210110
Received: June 10, 2009
Revised: July 29, 2009
Accepted: August 5, 2009
Published online: August 28, 2009
AIM: To identify the distribution of hepatitis B virus (HBV) subgenotype and basal core promoter (BCP) mutations among patients with HBV-associated liver disease in Indonesia.
METHODS: Patients with chronic hepatitis (CH, n = 61), liver cirrhosis (LC, n = 62), and hepatocellular carcinoma (HCC, n = 48) were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.
RESULTS: HBV genotype B (subgenotypes B2, B3, B4, B5 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis.
CONCLUSION: HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.
