HBV感染患者氧化应激状态与病毒基因型和耐药突变的相关性

Relationship between oxidative stress in patients with HBV-induced liver disease and HBV genotype/drug-resistant mutation

目的探讨慢性乙型肝炎患者氧化应激(OxS)状态和疾病严重程度与乙型肝炎病毒(HBV)基因型和耐药突变的相关性。方法 2014年2月至2016年4月该院确诊的乙型肝炎病毒感染患者296例,其中慢性乙型肝炎(CHB)145例,肝硬化(HBC)101例,CHB相关原发性肝癌(HCC)50例。采用PCR-反向点杂交法检测3种HBV基因型(B、C、D型)和8种耐药突变基因(t180L、rt204M、rt207V、rt236N、rt250M、rt181A、rt184T、rt202S);同时,检测总氧化态(TOS)和总抗氧化态(TAS),并计算OxS指数(OSI)。比较不同肝病、不同基因型及有无耐药突变患者之间TOS、TAS、OSI的差异,并分析HBV基因型、耐药突变、患者OxS与肝病严重程度的相关性。结果 CHB、HBC和HCC患者血清TOS和OSI,以及C型比值和耐药突变率依次增高(均P<0.05);血清TAS则依次降低,但CHB患者和HBC患者之间差异无统计学意义(P>0.05)。除HBC患者TAS水平外,耐药突变患者的TOS和OSI水平升高,而TAS水平降低,与无突变患者比较,差异有统计学意义(P<0.05),且耐药突变发生与血清TOS(r=0.476,P<0.01)和OSI(r=0.441,P<0.01)水平呈正相关,与TAS(r=―0.249,P<0.01)水平呈负相关;突变位点数与HBV感染后病情严重程度呈正相关(r=0.614,P<0.01)。结论 HBV感染患者存在不同程度的氧化损伤,其程度随病毒基因型和耐药突变不同而有所差异。因此,OxS参数可能是反映HBV感染患者疾病进展的有用指标。

Objective To explore the correlation of oxidative stress in patients with chronic hepatitis B and degree of severity of the disease with HBV genotype and drug-resistant mutation.Methods A total of 296 patients with diagnosed chronic hepatitis B were selected from Feb.2014 to Apr.2016 in Mianyang Central Hospital,included 145 patients with chronic hepatitis B（CHB）,101 patients with hepatitis B cirrhosis（HBC）and50 patients with CHB-related hepatocellular carcinoma（HCC）.Three HBV genotypes（B,C and D）and eight drug-resistant mutation genes（rt180 L,rt204 M,rt207 V,rt236 N,rt250 M,rt181 A,rt184 T,rt202 S）were detected by PCR-reverse dot blot method.In addition,total oxidative stress（TOS）,and total antioxidant status（TAS）were measured,on the basis of which oxidative stress index（OSI）was calculated.Furthermore,then the differences of TOS,TAS and OSI levels were compared between different liver diseases,different genotypes or drug-resistant mutation,and also the correlations were analyzed between HBV genotype,drug-resistant mutation,patient′s oxidative stress status and disease severity.Results Serum TOS and OSI levels,HBVC ratios and drug-resistant mutation rates were increased gradually with the severity of liver disease（CHB〈HBC〈HCC,P〈0.05）.Serum TAS levels decreased with degree of severity of the disease,but there was no statistical difference between CHB group and HCC group（P〉0.05）.Except TAS levels in patients at HBC group,compared with patients without mutation in HBV,the patients with drug-resistant mutation had higher TOS and OSI levels,but lower serum TAS levels（P〈0.05）.Drug-resistant mutation rate positively correlated with TOS（r=0.476,P〈0.01）and OSI（r=0.441,P〈0.01）,but negatively correlated with TAS（r=―0.249,P〈0.01）,except TAS level in patients at HBC group.In addition,the number of mutation sites was positively correlated with disease severity（r=0.614,P〈0.01）.Conclusion There are different degrees of oxidative damage in patients with HBV-induced liver disease,and the degree of the damage depends on HBV genotypes and drug-resistant mutations.Therefore,oxidative stress parameters might be useful indicators of progression of HBV-induced liver disease in patients.