抗线粒体抗体阴性原发性胆汁性肝硬化患者的临床及病理学特点

Clinical and pathological features of primary biliary cirrhotic patients with negative anti-mitochondria antibody

目的 分析抗线粒体抗体（AMA）阴性的原发性胆汁性肝硬化（PBC）患者临床及病理学特点.方法 对208例PBC患者的临床及病理学资料进行分析,并将AMA阴性PBC患者与典型PBC和自身免疫性肝炎（AIH）患者进行比较.非正态连续变量的比较使用Mann Whitney U检验,分类资料构成比的比较使用Chi-Square检验.结果 208例PBC患者中,AMA阴性者30例,占14.4%.AMA/AMA-M2阳性PBC和AMA阴性PBC患者在一般情况,临床表现、体征、肝功能（ALT、AST,碱性磷酸酶、γ-谷氨酰转移酶和总胆红素）和肝组织学表现上的差异均无统计学意义（P值均〉0.05）.AMA/AMA-M2阳性PBC组患者γ-球蛋白、IgG、IgM和IgA明显升高,中位数（P25,P75）分别为8.6（6.6,10.9）g/L,16.8（13.7,19.4）g/L、3.6（2.7,5.4）g/L和2.9（2.2,3.8）g/L,与AMA阴性组[分别为7.1（5.6,7.9）g/L、14.1（11.3,17.6）g/L、2.7（1.9,4.5）g/L和2.1（1.5,3.4）g/L]相比,差异有统计学意义（Z值分别为-2.088、-2.177、-2.372和-2.764,P值均〈0.05）;两组间总胆固醇差异无统计学意义（P〉0.05）.AMA阴性PBC患者中,29例（96.7%）呈抗核抗体（ANA）阳性,其中胞质颗粒型14例（48.3%）、核膜型8例（27.6%）、着丝点型6例（20.7%）、均质型1例（3.4%）.与AIH患者比较,AMA阴性PBC患者以胆汁淤积表现为主,碱性磷酸酶、γ-谷氨酰转移酶、IgM和胆固醇水平均较AIH组明显升高（P值均〈0.05）,而血清AST,IgG和IgA水平低于AIH患者（P值均〈0.05）.结论 在以胆汁淤积表现为主,IgM和胆固醇水平升高、ANA为非均质型为主要表现的患者中,AMA虽阴性仍需考虑PBC的可能.

Objective To explore the clinical and pathological features of primary biliary cirrhosis （PBC） patients with negative anti-mitochondria antibody （AMA）. Methods Two hundreds and eight PBC patients were enrolled. The clinical and histological data of the negative AMA cases were compared with the AMA/AMA-M2 positive cases. Results 30 out of the 208 cases （14.4%） were AMA negative patients in our study. The general status, biochemical tests and histological findings between the two groups had no significant difference （P〉 0.05）. The γ -globulin, IgG, IgM and IgA levels of AMA/AMA-M2 positive PBC patients were higher than that of the AMA negative cases （P 〈 0.05）. The abnormal rate of cholesterol in AMA negative PBC patients was 65.4% as compared to 50.4% in AMA/AMA-M2 positive cases, no significant difference existed between （P 〉 0.05）. Anti-nuclear antibody （ANA） was observed in 29 （96.7%） AMA negative PBC patients, including 14 （48.3%） with granular pattern, 8 （27.6%） with nuclear membrane pattern, 6 （20.7%） with kinetochore pattern and 1 （3.4%） with homogeneous pattern. AMA negative PBC patients had elevated serum ALP, GGT, IgM and cholesterol levels, and decreased serum AST, IgG and IgA levels as compared with that of autoimmune hepatitis patients （P 〈 0.05, respectively）. Conclusion In cholestatic patients with elevated IgM and cholesterol levels, ANA positive with non-homogeneous pattern, the diagnosis of PBC should be suspected, albeit AMA negative. The clinical, biochemcial and histological features of the AMA negative PBC patients were similar to classic PBC patients, but quite different from autoimmune hepatitis.