慢性丙型肝炎感染患者内源性循环红细胞自体抗体与贫血的相关性研究

Correlation between circulating autoantibodies to endogenous erythropoietin and anemia in patients with chronic hepatitis C infection

目的研究内源性循环红细胞(EPO)自体抗体与慢性丙型肝炎感染相关的贫血之间的关联性。方法收集孝昌县第一人民医院2014年1月-2016年8月被诊断出丙型肝炎病毒感染的抗病毒治疗患者的人口学和临床检查信息,共有121名患者纳入本研究。采用酶联免疫吸附试验测定患者血清抗EPO抗体水平,采用商用试剂盒测定血清中EPO水平,RT-PCR法测定丙型肝炎病毒RNA水平。多变量logistic回归分析血清抗EPO抗体与慢性丙型肝炎病毒感染相关的贫血之间的关联性。结果慢性丙型肝炎病毒感染患者中共有53名贫血和67名非贫血患者,贫血患者年龄、网织红细胞比例、血清EPO水平和抗EPO抗体阳性率均高于非贫血组。但血红蛋白、白蛋白和丙型肝炎病毒RNA负荷水平均低于非贫血组。慢性丙型肝炎病毒感染伴随抗EPO抗体阳性患者的血清EPO水平较低(P<0.001),但丙型肝炎病毒RNA负载却呈现出较高的水平(P<0.001)。慢性丙型肝炎病毒感染伴随抗EPO抗体阴性患者中血清EPO水平与血红蛋白水平呈现出负向相关性(P<0.001),并呈现出明显的反向剂量反应关系,但该相关性并未在抗EPO阳性患者中发现。多变量logistic回归分析发现网织红细胞比例每增加1%,血清EPO水平每增加1 mU/mL,贫血发生风险分别增加32.2%、8.9%,抗EPO抗体阳性患者贫血发生风险增高5倍。结论丙型肝炎病毒相关性贫血的发生与自身免疫有关。慢性丙型肝炎病毒感染伴随抗EPO抗体阳性患者有较高的贫血发生风险。

Objective To investigate the correlation between circulating autoantibody to endogenous erythropoietin(EPO) and anemia in patients with chronic hepatitis C(HCV) infection. Methods Information of demographic and clinical examination of 121 patients with HCV infection and accepted antiviral treatment were collected in Xiaochang First People’s Hospital from January 2014 to August 2016. Levels of serum anti-EPO antibody and EPO were detected by ELISA and a commercial kit, respectively. RT-PCR was used to determine HCV RNA levels. Multivariate logistic regression was used to evaluate the association between serum anti-EPO antibody and chronic HCV infection associated anemia. Results There were 53 and 67 chronic HCV infected patients with and without anemia, respectively. Higher levels of age, percent of reticulocyte, serum EPO and proportion of patients with positive anti-EPO antibody and lower levels of hemoglobin, albumin and HCV RNA were found among groups of anemia than non-anemia group. HCV infected patients with positive anti-EPO antibody had lower levels of serum EPO and higher levels of HCV RNA than patients with negative anti-EPO antibody(P < 0.001). A negative association and a reversed dose-response relationship between serum EPO and hemoglobin were found in patients with negative anti-EPO antibody(P < 0.001), but such results were not found among patients with positive anti-EPO antibody. Further, in the multiple logistic regression models, it was found that 1% increase in percent of reticulocyte and 1 mU/mL increasing in serum EPO were associated with 32.2% and 8.9% increased risk of anemia, while 5-fold increased anemia risk was found in chronic HCV infected patients with positive anti-EPO antibody. Conclusion The occurrence of hepatitis C virus-related anemia is associated with autoimmunity, and high risk of anemia is found among chronic HCV infected patients with positive serum anti-EPO antibody.