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Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia
Authors: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
Affiliation:1. Molecular Epidemiology Division,Mochtar Riady Institute for Nanotechnology,Lippo Karawaci,Tangerang,Banten 15810,Indonesia
2. Hepatology Division,Department of Internal Medicine,Faculty of Medicine,University of Indonesia,Jakarta 10430,Indonesia
3. Center of Gastroentero-Hepatology,Department of Internal Medicine,Faculty of Medicine,Hasanuddin University,Makassar 90245,Indonesia
4. Department of Internal Medicine,Mataram General Hospital,Mataram 83127,Indonesia
5. Gastroentero-Hepatology Division,Department of Internal Medicine,Gatot Soebroto Hospital,Jakarta 10410,Indonesia
6. Department of Internal Medicine,Siloam Hospital Lippo Karawaci,Tangerang,Banten 15810,Indonesia
Abstract:
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.
Keywords:Basal core promoter mutation  Hepatitis B virus  Indonesia  Liver disease  Subgenotype
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