Characterization of hepatitis B virus genotypes/subgenotypes in 1301 patients with chronic hepatitis B in North China  

作　　者：LI Xiao-dong WANG Lin LIU Yan XU Zhi-hui DAI Jiu-zeng LI Le YAO Zeng-tao XIN Shao-jie XU Dong-ping ZHAO Jing-ming 

机构地区：[1]Institute of Infectious Diseases and Liver Failure Research Center Beijing 302 Hospital, Beijing 100039, China [2]Department of Pathology Beijing 302 Hospital, Beijing 100039, China

出　　处：《Chinese Medical Journal》2011年第24期4178-4183,共6页中华医学杂志（英文版）

基　　金：This work was supported by the grants from the Beijing Natural Science Foundation （No. 7091006）, the National Key Basic Research Developing Project （No. 2007CB512803）, and the National 11th Five-Year Special Grand Project for Infectious Diseases （No. 2008ZX10002-011 and No. 2009ZX10004-314）. Conflict of interests： None.

摘　　要：Background There is still a paucity of data on hepatitis B virus （HBV） subgenotype prevalence in North China based on sequencing of large-size samples. In addition, whether HBV genotypes impact drug-resistance-associated and HBV e antigen （HBeAg）-Ioss-associated mutations in patients with chronic hepatitis B （CHB） is still under investigation. This study aimed to disclose clinical prevalence of HBV genotypes/subgenotypes in North China and the clinical implications of HBV genotype classification in respect to HBeAg loss and drug-resistant occurrence. Methods Sera were collected from 1301 nucleos（t）ide analog-experienced CHB patients. Viral DNA was extracted and used as template for HBV genome amplification by nested PCR. DNA sequencing was performed for the analysis of HBV genotypes/subgenotypes, drug-resistance-associated mutations in polymerase gene and HBeAg-loss-associated mutations in precore/basal core promoter （BCP） regions. Results HBV/B, HBV/C, and HBV/D were detected in 190 （14.6%）, 1096 （84.2%）, and 15 （1.2%） patients, respectively. HBV/B2 （182/190）, HBV/C2 （1069/1096）, and HBV/D1 （12/15） were predominant subgenotypes within individual genotypes. By contrast, C2 prevalence is relatively lower in Beijing area （77.2%） than in other north areas （84.9%-87.4%）. HBV/C-infected patients had an older age and a lower serum albumin level but similar HBV DNA and alanine aminotransferase （ALT） levels compared to HBV/B-infected patients. HBV/C infection had a higher incidence of lamivudine-resistant mutations rtM2041N （44.9% vs. 30.2%, P 〈0.01） and BCP mutations A1762T＋G1764A （65.8% vs. 40.0%, P〈0.01） compared with HBV/B infection. Conclusions C2 is the most prevalent HBV subgenotype followed by B2 in CHB patients in North China; and HBV genotype prevalence is influenced by immigrant population. HBV/C infection is likely to have longer disease duration and severer liver functional impairment and might be more susceptible to develop lamivudine resBackground There is still a paucity of data on hepatitis B virus （HBV） subgenotype prevalence in North China based on sequencing of large-size samples. In addition, whether HBV genotypes impact drug-resistance-associated and HBV e antigen （HBeAg）-Ioss-associated mutations in patients with chronic hepatitis B （CHB） is still under investigation. This study aimed to disclose clinical prevalence of HBV genotypes/subgenotypes in North China and the clinical implications of HBV genotype classification in respect to HBeAg loss and drug-resistant occurrence. Methods Sera were collected from 1301 nucleos（t）ide analog-experienced CHB patients. Viral DNA was extracted and used as template for HBV genome amplification by nested PCR. DNA sequencing was performed for the analysis of HBV genotypes/subgenotypes, drug-resistance-associated mutations in polymerase gene and HBeAg-loss-associated mutations in precore/basal core promoter （BCP） regions. Results HBV/B, HBV/C, and HBV/D were detected in 190 （14.6%）, 1096 （84.2%）, and 15 （1.2%） patients, respectively. HBV/B2 （182/190）, HBV/C2 （1069/1096）, and HBV/D1 （12/15） were predominant subgenotypes within individual genotypes. By contrast, C2 prevalence is relatively lower in Beijing area （77.2%） than in other north areas （84.9%-87.4%）. HBV/C-infected patients had an older age and a lower serum albumin level but similar HBV DNA and alanine aminotransferase （ALT） levels compared to HBV/B-infected patients. HBV/C infection had a higher incidence of lamivudine-resistant mutations rtM2041N （44.9% vs. 30.2%, P 〈0.01） and BCP mutations A1762T＋G1764A （65.8% vs. 40.0%, P〈0.01） compared with HBV/B infection. Conclusions C2 is the most prevalent HBV subgenotype followed by B2 in CHB patients in North China; and HBV genotype prevalence is influenced by immigrant population. HBV/C infection is likely to have longer disease duration and severer liver functional impairment and might be more susceptible to develop lamivudine res

关 键 词：hepatitis B virus GENOTYPE drug resistance PRECORE basal core promoter mutation 

分 类 号：R512.62[医药卫生—内科学]