慢性丙型肝炎患者血清自身抗体检测的研究

目的观察慢性丙型肝炎患者血清自身抗体检测结果,探讨自身免疫在丙型肝炎病毒(HCV)感染中的意义。方法回顾性分析北京大学第一医院慢性丙型肝炎患者自身抗体的阳性情况,并探讨HCVRNA含量、HCV基因型、肝硬化发生率、干扰素治疗应答率、年龄、性别及肝功能与自身抗体的关系。结果(1)69例慢性丙型肝炎患者中有20例出现自身抗体阳性,检出率为28.9%(20/69),自身抗体以低滴度为主,主要为抗核抗体,明显高于慢性乙肝组的自身抗体检出率4.3%(3/69,P<0.05);明显低于自身免疫性肝炎组的自身抗体检出率100%(P<0.05)。(2)慢性丙型肝炎患者自身抗体阴性、阳性组之间HCVRNA含量、HCV基因型比较差异无统计学意义。(3)慢性丙型肝炎患者经α干扰素抗病毒治疗后,自身抗体阳性组干扰素应答率(77.8%)高于自身抗体阴性组应答率(51.2%,P<0.05)。(4)自身抗体在年龄长者中检出率较高,差异有统计学意义(P<0.05),而与性别无关。(5)自身抗体阳性组肝硬化发生率(80%)高于阴性组(46.9%,P<0.05)。(6)自身抗体阳性的慢性丙型肝炎患者的血清丙氨酸氨基转移酶(ALT)、谷氨酸氨基转移酶(AST)、总胆红素(TBIL)以及γ球蛋白均高于自身抗体阴性患者(分别为191U/L±89U/Lvs113U/L±69U/L,169U/L±80U/Lvs98U/L±62U/L,78μmol/L±50μmol/Lvs51μmol/L±30μmol/L,200g/L±80g/Lvs160g/L±70g/L,均P<0.05)。结论HCV感染能诱导自身免疫反应,使患者血清出现多种自身抗体,自身抗体的检出率与肝硬化和年龄明显有关,检测其自身抗体及其滴度对丙型肝炎患者的临床诊疗具有指导意义。

Serum autoantibodies of patients with chronic hepatitis C and the significance thereof in infection of hepatitis C virus

OBJECTIVE: To investigate the serum autoantibodies in patients with chronic hepatitis C and to investigate the significance of autoimmune reaction in hepatitis C virus (HCV) infected patients. METHODS: Peripheral blood samples were collected from 69 patients with chronic hepatitis C, 69 patients with chronic hepatitis B (HB), and 69 patients with autoimmune hepatitis (AIH). Indirect immunofluorescence technique was used to detect the serum anti nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (anti-SMA), and anti-liver-kidney antibody (anti-LKM). HCV RNA was detected by PCR. The biochemical indices: alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and gamma-globulin were detected. The relations of autoantibodies to virus load, HCV genotype, cirrhosis, age, sex, and liver function were analyzed. RESULTS: (1) Twenty of the HCV patients were positive in autoantibodies, most being at a low titer, 11 of them being positive in ANA, 7 in anti-SMA, 1 in anti-AMA, and 1 in anti-LKM, with a positive rate of 28.9%, significantly higher than that of the HB patients (4.3%, P < 0.05), and significantly lower than that of the AIH patients (100%, P < 0.05). (2) There were no significant differences between the autoantibody positive group and autoantibody negative group in virus load and HCV genotype. (3) Fourteen of the 18 patients positive in autoantibodies responded to the anti-virus treatment with alpha-interferon with a response rate of 77.8%, significantly higher than that of the autoantibody negative group (53%, P < 0.05). (4) The average age of the autoantibody positive group was 47 +/- 18 years, significantly higher than that of the autoantibody negative group (39 +/- 12 years, P < 0.05). The positive autoantibody rate of the patients aged >or= 40 was 23.1%, significantly higher than that of the patients aged < 40 (5.8%, P < 0.05). There was no significant difference in the autoantibody rate between males and females. (5) The cirrhosis prevalence rate of the autoantibody positive group was 80%, significantly higher than that of the autoantibody negative group (46.9%, P < 0.05). (6) The serum ALT, AST, TBIL and gamma-globulin of the autoantibody positive group were 191 U/L +/- 89 U/L, 169 U/L +/- 80 U/L, 78 micromol/L +/- 50 micromol/L, and 200 g/L +/- 80 g/L respectively, all significantly higher than those of the autoantibody negative group (113 U/L +/- 69 U/L, 98 U/L +/- 62 U/L, 51 micromol/L +/- 30 micromol/L, and 160 g/L +/- 70 g/L respectively, all P < 0.05). (7) There were no significant differences in HCV RNA load and HCV genotype between the autoantibody positive group and the autoantibody negative group (both P > 0.05). CONCLUSION: HCV infection induces the autoimmune reaction resulting in production of autoantibodies. Positive autoantibody rate is related with cirrhosis and age. Titer and type of autoantibody serve as important indices in the diagnosis and treatment of HCV.