Naturally occurring mutations in the reverse transcriptase region of hepatitis B virus polymerase from treatment-na?ve Korean patients infected with genotype C2

作     者：Ji-Eun Kim So-Young Lee Hong Kim Ki-Jeong Kim Won-Hyeok Choe Bum-Joon Kim 

作者机构：Department of Biomedical SciencesMicrobiology and Immunologyand Liver Research InstituteSeoul National University College of Medicine Department of MicrobiologySchool of MedicineJoong-Ang University Department of Internal MedicineKonkuk University School of Medicine 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2017年第23卷第23期

页      面：4222-4232页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：Supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology No.NRF-2015R1C1A1A02037267 Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health and Welfare,South Korea,No.HI14C0955 

主　　题：Hepatitis B virus Polymerase Reverse transcriptase Potential nucleos(t)ide analog resistance Chronic hepatitis Hepatocellular carcinoma 

摘      要：AIM To report naturally occurring mutations in the reverse transcriptase region(RT) of hepatitis B virus(HBV) polymerase from treatment na?ve Korean chronic patients infected with genotype *** Here, full-length HBV reverse transcriptase RT sequences were amplified and sequenced from 131 treatment na?ve Korean patients chronically infected with hepatitis B genotype C2. The patients had two distinct clinical statuses: 59 patients with chronic hepatitis(CH) and 72 patients with hepatocellular carcinoma(HCC). The deduced amino acids(AAs) at42 previously reported potential nucleos(t)ide analog resistance(NAr) mutation positions in the RT region were analyzed. RESULTS Potential NAr mutations involving 24 positions were found in 79 of the 131 patients(60.3%). Notably, AA substitutions at 2 positions(rt184 and rt204) involved in primary drug resistance and at 2 positions(rt80 and rt180) that functioned as secondary/compensatory mutations were detected in 10 patients(1 CH patient and 9 HCC patients) and 7 patients(1 CH and 6 HCC patients), respectively. The overall mutation frequencies in the HCC patients(3.17%, 96/3024 mutations) were significantly higher than the frequencies in the CH patients(2.09%, 52/2478 mutations)(P = 0.003). In addition, a total of 3 NAr positions, rt80, rt139 and rt204 were found to be significantly related to HCC from treatment na?ve Korean patients. CONCLUSION Our data showed that naturally occurring NAr mutations in South Korea might contribute to liver disease progression(particularly HCC generation) in chronic patients with genotype C2 infections.