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©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
Hepatitis B virus pre-S2 start codon mutations in Indonesian liver disease patients
Andi Utama, Marlinang Diarta Siburian, Ismail Fanany, Mariana Destila Bayu Intan, Rama Dhenni, Tri Shinta Kurniasih, Syafruddin AR Lelosutan, Wenny Astuti Achwan, Nasrul Zubir, Arnelis, Benyamin Lukito, Irawan Yusuf, Laurentius Adrianus Lesmana, Ali Sulaiman
Andi Utama, Marlinang Diarta Siburian, Ismail Fanany, Mariana Destila Bayu Intan, Rama Dhenni, Tri Shinta Kurniasih, Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Lippo Karawaci, Tangerang 15810, Banten, Indonesia
Syafruddin AR Lelosutan, Gastroentero-Hepatology Division, Department of Internal Medicine, Gatot Soebroto Hospital, Jakarta 10410, Indonesia
Wenny Astuti Achwan, Department of Internal Medicine, Mataram General Hospital, Mataram 83127, Indonesia
Nasrul Zubir, Arnelis, Gastroentero-Hepatology Division, Department of Internal Medicine, M. Djamil Hospital, Padang 25127, Indonesia
Benyamin Lukito, Department of Internal Medicine, Siloam Hospital Lippo Karawaci, Tangerang 15810, Banten, Indonesia
Irawan Yusuf, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia
Laurentius Adrianus Lesmana, Ali Sulaiman, Hepatology Division, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia
Author contributions: Utama A designed the study and prepared the manuscript; Siburian MD, Fanany I, Intan MDB, and Kurniasih TS performed the experiments; Dhenni R performed sequence and statistic analysis; Lelosutan SAR, Achwan WA, Arnelis, Lukito B, Yusuf I, Zubir N, Lesmana LA, and Sulaiman A coordinated and provided the collection of human materials and were involved in editing the manuscript.
Supported by MRIN Funding, Budget, No. cc041/2010
Correspondence to: Andi Utama, PhD, Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Jalan Boulevard Jend. Sudirman 1688, Lippo Karawaci, Tangerang 15810, Banten, Indonesia. autama@mrinstitute.org
Telephone: +62-21-54210123 Fax: +62-21-54210110
Received: February 14, 2012
Revised: April 12, 2012
Accepted: April 20, 2012
Published online: October 14, 2012
AIM: To identify the prevalence of pre-S2 start codon mutations and to assess their association with liver disease progression.
METHODS: The mutations were identified by direct sequencing from 73 asymptomatic carriers, 66 chronic hepatitis (CH), 66 liver cirrhosis (LC) and 63 hepatocellular carcinoma (HCC) patients. Statistical significances were determined using Fisher’s exact test, χ2 test, and t-test analyses whenever appropriate. Pre-S mutation as a risk factor for advanced liver disease was estimated by unconditional logistic regression model adjusted with age, sex, and hepatitis B e antigen (HBeAg). P < 0.05 was considered significant.
RESULTS: Mutation of the hepatitis B virus (HBV) pre-S2 start codon was found in 59 samples from 268 subjects (22.0%), with higher prevalence in patients with cirrhosis 27/66 (40.9%) followed by HCC 18/63 (28.6%), chronic hepatitis 12/66 (18.2%) and asymptomatic carriers 2/73 (2.7%) (P < 0.001). Logistic regression analysis showed that pre-S2 start codon mutation was an independent factor for progressive liver disease. Other mutations, at T130, Q132, and A138, were also associated with LC and HCC, although this was not statistically significant when adjusted for age, sex, and HBeAg. The prevalence of pre-S2 start codon mutation was higher in HBV/B than in HBV/C (23.0% vs 19.1%), whilst the prevalence of T130, Q132, and A138 mutation was higher in HBV/C than in HBV/B. The prevalence of pre-S2 start codon mutation was higher in LC (38.9%) and HCC (40.0%) than CH (5.6%) in HBeAg(+) group, but it was similar between CH, LC and HCC in HBeAg(-) group.
CONCLUSION: Pre-S2 start codon mutation was higher in Indonesian patients compared to other Asian countries, and its prevalence was associated with advanced liver disease, particularly in HBeAg(+) patients.
