乙型肝炎病毒与戊型肝炎病毒重叠感染患者T淋巴细胞变化及相关临床危险因素分析

Analysis of T lymphocyte changes and related clinical risk factors in patients with hepatitis B virus and hepatitis E virus superinfection

目的探讨乙型肝炎病毒(HBV)与戊型肝炎病毒(HEV)重叠感染患者的T淋巴细胞亚群变化特点,并寻找与重叠感染相关的临床危险因素。方法以2001年8月至2012年7月新乡医学院第一附属医院收治的28例HEV感染患者及首都医科大学附属北京佑安医院收治的58例HEV感染患者为观察对象,根据是否同时存在HBV感染分为HEV感染组74例和重叠感染组12例,应用生物化学方法检测血生物化学指标,免疫法检测病毒抗体,流式细胞术检测T淋巴细胞亚群,免疫比浊法检测免疫5项,并对2组患者的检测结果进行比较。采用χ~2检验连续校正、Mann-Whitney-U检验和t'检验比较2组之间各项指标的差异,logistic多因素回归分析确定与HBV重叠HEV感染独立相关的危险因素,Spearman法分析2组间有统计学差异的临床参数与T淋巴细胞亚群及免疫5项之间的相关性。结果重叠感染组患者的年龄、丙氨酸氨基转移酶和凝血酶原活动度(PTA)均低于HEV感染组(Z=-3. 588、-2. 044,t'=-6. 720,P <0. 05)。2组患者性别构成、住院时间及天冬氨酸氨基转移酶、总胆红素、直接胆红素、γ-谷氨酰转移酶、白蛋白、甲胎蛋白、碱性磷酸酶、空腹血糖、胆固醇水平比较差异均无统计学意义(P> 0. 05)。重叠感染组患者CD8+T淋巴细胞计数显著低于HEV感染组(Z=-2. 175,P <0. 05),CD4+T/CD8+T显著高于HEV感染组(Z=-2. 091,P <0. 05)。2组患者CD3+T淋巴细胞计数、CD4+T淋巴细胞计数及Ig A、Ig M、Ig G、C3、C4水平比较差异无统计学意义(P> 0. 05)。PTA与HBV重叠感染HEV相关(OR=1. 056,95%可信区间为1. 009~1. 105,P <0. 05)。PTA与C3水平呈正相关(r=0. 370,P <0. 05),与Ig A水平呈负相关(r=-0. 530,P <0. 05)。结论 CD8+T淋巴细胞在HBV重叠感染HEV患者中明显下降,PTA是重叠感染的独立危险因素,针对CD8+T淋巴细胞和PTA改善肝细胞功能的治疗策略可能是HBV重叠感染HEV患者临床治疗的一种选择。

Objective To investigate the characteristics of T lymphocyte subsets in patients with hepatitis B virus （HBV） and hepatitis E virus （HEV） superinfection,and to analyze the clinical risk factors for superinfection.Methods A total of 28 patients with HEV infection in the First Affiliated Hospital of Xinxiang Medical University and 58 patients with HEV infection in Beijing You′an Hospital Affiliated to Capital Medical University from August 2001 to July 2012 were selected as the subjects.The patients were divided into HEV infection group （ n =74） and superinfection group （ n =12） according to whether the patients had HBV infection.Blood biochemical indexes were detected by biochemical method,virus antibody was detected by immunoassay,T lymphocyte subsets were detected by flow cytometry,the five immunological indexes were detected by immunoturbidimetry,and the detection results were compared between the two groups.The independent risk factors of HBV and HEV superinfection were analyzed by multivariate logistic regression.The correlation between clinical parameters and T lymphocyte subsets or five immunological indexes was analyzed by spearman method.Results The age,aspartate aminotransferase and prothrombin activity（PTA） in the superinfection group were lower than those in the HEV infection group （ Z =-3.588 ,-2.044; t ′=-6.720; P 〈0.05）.There was no significant difference in the male proportion,hospitalization time and the levels of aspartate aminotransferase,total bilirubin,direct bilirubin,γ-glutamyl transferase,albumin,alpha fetoprotein,alkaline phosphatase,fasting blood glucose and cholesterol between the two groups （ P 〉0.05）.The levels of CD8 ＋ T lymphocyte in the superinfection group was significantly lower than that in the HEV infection group（ Z =-2.175, P 〈0.05）,the levels of CD4 ＋T/CD8 ＋T in the superinfection group was significantly higher than that in the HEV infection group（ Z = -2.091 , P 〈0.05）.There was no significant difference in the levels of CD3 ＋ T lymphocyte,CD4 ＋ T lymphocyte,IgA,IgM,IgG,C3 and C4 between the two groups （ P 〉0.05）.PTA was associated with HBV and HEV superinfection （ OR =1.056,95% confidence interval：1.009-1.105; P 〈0.05）.PTA was positively correlated with C3 level （ r =0.370, P 〈0.05）.PTA was negatively correlated with IgA level （ r =-0.53, P 〈0.05）.Conclusions The level of CD8 ＋T lymphocyte decrease significantly in patients with HBV and HEV superinfection.PTA is an independent risk factor for superinfection.Therapeutic strategies targeting CD8 ＋ T lymphocyte and PTA to improve hepatocyte function may be an option for clinical treatment of the patients with HBV and HEV superinfection.