郴州地区静脉吸毒人群肝炎病毒感染状况以及共感染对病毒清除影响

Analysis of hepatitis virus infection status and influence of coinfection on vi⁃rus clearance in intravenous drug users in Chenzhou area

目的了解郴州地区静脉吸毒人群中乙型肝炎病毒(hepatitis B virus,HBV)、丙型肝炎病毒(hepatitis C virus,HCV)和丁型肝炎病毒(hepatitis D virus,HDV)的感染状况及基因型的分布特征;探究共感染患者病毒载量的水平变化以及HBV/HCV共感染中病毒相互作用的影响因素。方法收集2014~2018年郴州市戒毒所和美沙酮门诊中静脉吸毒志愿者血样,排除艾滋、梅毒等感染性疾病后共纳入样本2909例。使用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测血清中乙肝表面抗原(hepatitis B surface antigen,HBsAg)、丙型肝炎IgG抗体(hepatitis C IgG antibody,HCV-IgG)或丁型肝炎IgG抗体(hepatitis D IgG antibody,HDV-IgG)的水平。巢式聚合酶链反应(polymerase chain reaction,PCR)扩增感染样本的脱氧核糖核酸(deoxyribo nucleic acid,DNA)或核糖核酸(ribonucleic acid,RNA),测序鉴定其基因型,并通过Real-time PCR对病毒载量进行定量分析。结果(1)HBsAg、HCV-IgG和HDV-IgG在静脉吸毒人群血清中的阳性率分别为20.49%、34.03%、3.85%。(2)基因型分析发现HBV基因型以B型(86.74%)为主,C型(11.94%)相对少见;HCV基因6a型为主要感染型(51.33%),其次为3a(20.28%)、3b型(16.98%);HDV基因型均为Ⅱ型。(3)HCV单感染患者的HCV RNA病毒载量高于HBV/HCV共感染患者(P=0.007);HBV单感染患者的HBV DNA病毒载量高于HBV/HDV共感染患者(P=0.013)和HBV/HCV/HDV三重感染患者(P=0.042);HBV/HDV共感染患者HBsAg水平高于HBV单感染患者(P=0.003)和HBV/HCV共感染患者(P=0.004)。(4)Logistic回归模型分析结果表明HBsAg水平与慢性HCV感染的自发清除显著相关(OR=1.53,95%CI:1.19~1.96),HCV RNA载量可独立并且准确地预测HBV血清清除(OR=1.36,95%CI:1.03~1.80)。结论HBsAg而非HBV DNA是竞争HCV复制的主要因素,高HCV病毒载量可能有益于HBV感染的自发清除。

Objective To understand the infection status and genotype distribution of hepatitis B virus(HBV),hepatitis C virus(HCV)and hepatitis D virus(HDV)in the intravenous drug users in Chenzhou area,and to investigate the changes in viral load levels in co⁃infected pa⁃tients and the factors influencing viral interactions in HBV/HCV co⁃infection.Methods Blood samples were collected from intravenous drug users in drug rehabilitation centers and methadone clinics from 2014 to 2018 in Chenzhou City,and a total of 2,909 samples were in⁃cluded after excluding infectious diseases such as human immunodeficiency virus(HIV)and syphilis.The levels of hepatitis B surface antigen(HBsAg),hepatitis C IgG antibody(HCV⁃IgG)or hepatitis D IgG antibody(HDV⁃IgG)in the serum of all study subjects were measured using an enzyme⁃linked immunosorbent assay(ELISA).Deoxyribo nucleic acid(DNA)or ribo⁃nucleic acid(RNA)from infected samples was amplified by nested polymerase chain reaction(PCR),sequenced to identify their genotype and the viral load was quantified by Real⁃time PCR.Results The seropositivity rates for HBsAg,HCV IgG and HDV IgG in the intravenous drug users were 20.49%,34.03%and 3.85%,respectively;Genotype analysis showed that HBV genotypes were predominantly B(86.74%)and C(11.94%)were relatively rare;HCV genotype 6a was the main type of infection(51.33%),followed by 3a(20.28%)and 3b(16.98%);all HDV genotypes were typeⅡ;The HCV RNA viral load was higher in HCV mono⁃infected patients than in HBV/HCV co⁃infected patients(P=0.007);HBV DNA viral load was higher in HBV mono⁃infected patients than in HBV/HDV co⁃infected patients(P=0.013)and HBV/HCV/HDV triple⁃infected patients(P=0.042);HBsAg levels were higher in HBV/HDV co⁃infected patients than in HBV mono⁃infected patients(P=0.003)and HBV/HCV co⁃infected patients(P=0.004);Binary logistic regression showed that HBsAg levels were significantly associated with spontaneous clearance of chronic HCV infection(OR=1.53,95%CI:1.19~1.96)and that HCV RNA load independently and accurately predicted HBV serum clearance(OR=1.36,95%CI:1.03~1.80).Conclusion HBsAg rather than HBV DNA is the main factor competing for HCV replication.High HCV viral load may be ben⁃eficial for the spontaneous clearance of HBV infection.