Hepatitis B virus pre-S2 start codon mutations in Indonesian liver disease patients  

作　　者：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 

机构地区：[1]Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Lippo Karawaci, Tangerang 15810, Banten, Indonesia [2]Gastroentero-Hepatology Division, Department of Internal Medicine, Gatot Soebroto Hospital, Jakarta 10410, Indonesia [3]Department of Internal Medicine, Mataram General Hospital, Mataram 83127, Indonesia [4]Gastroentero-Hepatology Division, Department of Internal Medicine, M. Djamil Hospital, Padang 25127, Indonesia [5]Department of Internal Medicine, Siloam Hospital Lippo Karawaci, Tangerang 15810, Banten, Indonesia [6]Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia [7]Hepatology Division, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia

出　　处：《World Journal of Gastroenterology》2012年第38期5418-5426,共9页世界胃肠病学杂志（英文版）

基　　金：Supported by MRIN Funding, Budget, No. cc041/2010

摘　　要：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, χ 2 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.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, χ 2 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.

关 键 词：Hepatitis B virus Pre-S2 start codon Liver disease Hepatitis B e antigen seroconversion Indonesia 

分 类 号：R512.62[医药卫生—内科学]