慢性乙型肝炎病毒感染者病毒基因型分布及其与肝纤维化和肝细胞癌的关系

Distribution of hepatitis B virus genotypes and their correlations with liver fibrosis and hepatocellular carcinoma

目的 调查浙江省杭州地区慢性乙型肝炎病毒(HBV)感染者的HBV基因型分布,并分析基因型与肝纤维化和肝细胞癌的关系.方法 回顾性分析2007年6月至2012年6月在杭州市第一人民医院就诊的190例慢性HBV感染者的血清学、病毒学指标和临床病理学资料.190例患者根据病理及相关检测分为慢性乙型肝炎(CHB)组(62例)、肝硬化组(60例)和肝细胞癌组(68例).HBV基因型测定采用多重PCR扩增,基因亚型测定采用PCR扩增结合限制性片段长度多态性(RFLP)方法.采用SPSS 11.0软件进行统计学分析.结果 190例慢性HBV感染者中,B基因型感染61例(32.1％),C基因型感染126例(66.3％),3例为B、C基因混合型感染.其中,B基因型全部为B2亚型,C基因型中C2亚型占绝对优势(97.6％,123/126).B基因型在CHB组的比例(46.8％,29/62)高于肝硬化组(20.0％,12/60)和肝细胞癌组(29.4％,20/68)(x2=8.73和4.16,P＜0.01或＜0.05);C基因型在肝硬化组和肝细胞癌组的比例高于CHB组(x2=9.54和4.17,P＜0.01或＜0.05).三组患者中感染C2基因亚型的血清透明质酸(HA)水平高于感染B2基因亚型的患者(t=2.685,2.433和2.015,P＜0.01或＜0.05).CHB患者中感染C2基因亚型者比感染B2基因亚型者有更高的肝纤维化分期(x2=6.726,P=0.010),而肝脏炎症分级差异无统计学意义(x2=0.601,P＞0.05).肝细胞癌患者中,感染B2基因亚型者肿瘤直径≥5 cm的比例更高(x2=7.231,P＜0.01),感染C2基因型者伴肝硬化更常见(x2 =4.910,P＜0.05).结论 浙江省杭州地区CHB患者以C2和B2基因亚型为主.感染C2基因亚型的患者可能更易发展为严重肝纤维化,而感染B2基因亚型的患者和大肝癌相关.

Objective To investigate the distribution of hepatitis B virus (HBV) genotypes in patients with chronic HBV infections and the correlations of genotypes with liver fibrosis and hepatocellular carcinoma (HCC).Methods Serological,virological and pathological data of 190 patients with chronic HBV infections admitted to Hangzhou First People's Hospital during June 2007 and June 2012 were retrospectively analyzed.The series included 62 cases of chronic hepatitis B (CHB),60 cases of liver cirrhosis and 68 cases of HCC.HBV was genotyped by multiplex PCR,and subgenotyped by restriction fragment length polymorphism (RFLP).SPSS 11.0 was used for statistical analysis.Results Among 190 patients,61 were HBV genotype B (32.1％),126 were genotype C (66.3％),and 3 were B + C hybrid.HBV B2 (61/61,100.0％) and C2 (123/126,97.6％) were the major subgenotypes.HBV genotype B was more prevalent in CHB patients (46.8％,29/62) than in liver cirrhosis (20.0％,12/60) and in HCC patients (29.4％,20/68) (x2 =8.73 and 4.16,P＜0.01 or P＜0.05),whereas the prevalence of genotype C was higher in liver cirrhosis and HCC than that in CHB (x2 =9.54 and 4.17,P ＜0.01 or P ＜ 0.05).Patients with genotype C2 had higher serum hyaluronic acid level than with genotype B2 in 3 groups (t =2.685,2.433 and 2.015,P ＜ 0.01 or P ＜ 0.05).CHB patients with C2 infections had higher liver fibrosis grade than those with B2 (x2 =6.726,P =0.010),while there was no statistical difference in liver inflammation grade (x2 =0.601,P ＞ 0.05).HCC patients with B2 infection tended to have larger tumor diameter (≥5 cm) (x2 =7.231,P ＜ 0.01) and those with C2 infection were prone to be more serious cirrhosis (x2 =4.910,P ＜ 0.05).Conclusions HBV genotypes C2 and B2 are predominant in patients with chronic HBV infections in Hangzhou.HCC patients infected with HBV C2 may be complicated with more severe liver fibrosis,and those with HBV B2 infections may tend to have larger liver tumor.