抗HCV抗体水平在不同HCV感染人群中的临床意义评价

A preliminary assessment of the clinical utility of measuring hepatitis C virus antibody to evaluate infection status

目的比较HCV单感染、人类免疫缺陷病毒（HIV）／HCV共感染、HCV自发清除者血清HCV抗体S／CO比值低值与高值的分布情况，对HCV不同感染状态下HCV抗体检测的临床意义进行初步评价。方法2009年对河南上蔡某村的129例HCV单感染者、98例HIV／HCV共感染者、65例HIV阴性的HCV自发清除者和48例HIV阳性的HCV自发清除者的血清或血浆样本进行HCV抗体、HCVRNA、ALT、AST检测，对HCV慢性感染者和HIV感染者分别进行HCV基因型分析和CD4＋T淋巴细胞计数检测，将各组人群的各项指标进行对比分析。2012年对该调查人群进行随访采样并检测HCV抗体水平。计量资料组间比较采用t检验，计数资料采用疋。检验；相关分析采用Pearson检验。结果HCV慢性感染者的HCV抗体水平几乎均为高值分布（S／CO≥10），而HCV抗体低值（1≤S／CO〈10）主要分布在HCV自发清除者和HIV／HCV共感染者中；HCV自发清除者的抗体水平随着时间推移发生衰减（2012年与2009年比：HIV阴性组：5．51土3．67与7．75±3．8，f=10．67，P〈0．01；HIV阳性组：4．93±3．35与7．61±3．47，t=9．52，P〈0．01），而HCV慢性感染者无此变化；HIV／HCV共感染者的HCV抗体S／CO比值与CD4＋T淋巴细胞数呈正相关（r=0．28，P=0．008）。比较不同HCV基因型的慢性感染者，HCV单感染组HCV-lb型患者的HCV抗体水平高于HCV-2a型（14．74±1．68与14．08±1．44，t=2．20，P=0．03）；HIV／HCV共感染者中，HCV—Ib型血浆ALT／AST水平升高的患者比例显著高于HCV-2a型（ALT：25／42与16／56，x^2=9．45，P=0．002；AST：28／42与18／56，x^2=11．49，P=0．001）。将HCV抗体水平、HCVRNA以及血浆ALT／AST检测结果联合分析，无论是否合并HⅣ感染，HCV抗体高值组的HCVRNA阳性率显著高于HCV抗体低值组（HIV阴性：128／151与1／43，z。=102．11，P〈0．01；HIV阳性：88／98与10／48，x^2=69．44，P〈0．01）；在HIV阴性且HCV抗体为高值的人群中，HCV慢性感染者的肝功能受损率明显高于自发清除者（ALT：x^2=10．52，P〈0．01lAST：z。=16．45，P〈0．01）。结论在临床诊断实践中，可将HCV抗体S／CO值等于10作为HCV抗体高值和低值的分界值。在未经HCV抗病毒治疗的唇耆中7排除合并感染HIV等免疫损伤性疾病的可能性，低值HCV抗体水平（s／co〈10）的出现在很大程度上可判断患者为HCV自发清除者。HCV抗体水平结合临床其他信息（如肝脏损伤情况、HIV感染状态等）可初步评价患者的HCV感染状态。

Objective To investigate the potential of hepatitis C virus （HCV） antibody measurement as a clinical approach to determine the infection status and potential for spontaneous-resolution among patients with HCV mono-infection and HCV/human immunodeficiency virus （HIV） co-infection. Methods A total of 340 individuals who tested positive for serum anti-HCV antibodies and/or serum anti-HIV antibodies were enrolled for study in 2009 from a single village in central China. Markers of liver function （alanine aminotransferase （ALT） and aspartate aminolransfemse （AST）） and infection （anti-HCV antibodies, CD4＋ T cell counts, HCV genotype, and HCV viral load） were measured at baseline and follow-up （in July 2012）. At follow-up, the subjects were grouped according to ongoing HCV mono-infection （n = 129）, ongoing HCV/HIV co-infection （17 = 98）, spontaneously resolved （SR）-HCV in mono-infection （n = 65）, and SR-HCV in HCV/I-IIV co-infection （n = 48） for statistical analysis. Results Almost all of the subjects in the ongoing HCV mono-infection group showed high levels of HCV antibodies （S/CO 1〉 10）, but the majority of the subjects in the SR-HCV in mono-infection group and in the ongoing HCV/HIV co-infection group. The SR-HCV mono-infection group showed a remarkable decrease in HCV antibodies from 2009 （HIV-： 7.75± 3.8; HIV＋： 7.61 ±3.47） to 2012 （HIV： 5.51 ±3.67; HIV＋： 4.93 ±3.35） （HIV： t = 10.67, P 〈 0.01; I-IV＋： t = 9.52, P 〈 0.01）. The ongoing HCV/HIV co-infection group showed a positive correlation between HCV antibodies S/CO ratio and CD4＋ T cell count （r = 0.28,P = 0.008）. In the ongoing HCV mono-infection group, the levels of HCV antibodies were significantly higher in individuals infected with HCV-lb than in those with HCV-2a （14.74 ：L 1.68 vs. 14.08 q- 1.44, t = 2.20,P = 0.03）. In the ongoing HCV/HIV co-infection group, the numbers of subjects with elevated （〉 40 U/L） liver function markers were significantly different according to the HCV genotype infection： HCV-lb： ALT, 25/42 vs. 16/56 （22 = 9.45, P = 0.002）; HCV- 2a： AST, 28/42 vs. 18/56 （22 = 11.49,P = 0.001）. The HCV RNA positive rate was significantly higher in subjects with high HCV antibody cutoff values （S/CO ~ 10） than in those with low HCV antibody （S/CO 〈 10） （H/V： 128/151 vs. 1/43,22 = 102.11,P〈 0.01; HIV＋： 88/98 vs. 10/48,22 = 69.44,P 〈 0.01）, regardless of HIV co-infection. Significantly more subjects in the ongoing HCV mono-infection group had elevated （〉 40 U/L） ALT or AST than the subjects in the SR-HCV mono-infection group with high levels of HCV antibody （S/CO 10） （ALT： 57/128 vs. 2/23,2＇2 = 10.52, P = 0.001; AST： 57/128 vs. 0/23,22 = 16.45, P 〈 0.01）. Conclusion Serum HCV antibody levels, in combination with other clinical information such as liver function and HIV infection status, may aid in the preliminarily evaluation of an individual＇s HCV infection status and likelihood for spontaneous resolution. Low levels of HCV antibody （S/CO 〈 10） may indicate a better chance of SR-HCV, after ruling out the possibility of suffering from diseases such as HIV infection.