药物性肝损伤与自身免疫性肝炎患者的血清学和病理学特征分析

Serological and pathological features of drug-induced liver injury and autoimmune hepatitis

目的探讨药物性肝损伤（DILI）和自身免疫性肝炎（AIH）患者在血清生物化学检测指标和肝组织病理学上的差异与共同点，为临床诊治和鉴别这两种疾病提供思路。方法搜集2012年1月至2014年10月我院连续住院诊治的106例DILI患者和63例AIH患者的生物化学、免疫学、自身抗体及肝组织病理资料。分别统计一般资料、生物化学指标、免疫学、肝组织Ishak评分及肝组织定性改变并比较分析。多组非参数统计采用Kruskal-Wallis检验，多组间两组比较的非参数统计采用Nemenyi检验，肝组织Ishak评分采用Wilcoxon rank-sum检验，分类资料构成比的比较采用Chi-Square检验。结果AIH组分别与DILI肝细胞损伤型组和DILI混合型组患者各项血清生物化学检测指标比较，丙氨酸氨基转移酶（187．2U／L分别对比1326．5U／L、455．6U／L）、天冬氨酸氨基转移酶（172．2U／L分别对比759．5U／L、349．5U／L）、碱性磷酸酶（209．3U／L分别对比157．3U／L、169．4U／L）、γ-谷氨酰转移酶（254．8U／L分别对比176．5U／L、170．5U／L）、总胆红素（37．2μmol／L分别对比95．8μmol／L、52．6μmol／L）和血清铁（18．9μmol／L分别对比36．2μmol／L、23．9μmol／L）、血清铁蛋白（122．5μmol／L分别对比410．4μmol／L、186．5μmol／L）、免疫球蛋白（Ig）G（18．4g／L分别对比12．6g／L、12．3g／L）和IgM（1．8g／L分别对比1．3g／L、1．1g／L），P值均〈0．05，差异均有统计学意义。AIH组、DILI肝细胞损伤型组和DILI混合型组界面炎症Ishak评分分别为2．2±0．8、1．3±0．7、1．3±0．6，汇管区炎症Ishak评分分别为2．3±0．9、1．5±0．7、1．4±0．8，纤维化评分分别为2．8±1．1、1．5±0．7、1．3±0．7，AIH组与其他两组比较，P值均〈0．05，差异均有统计学意义。AIH组、DILI肝细胞损伤型组和DILI混合型组蜡质样沉积比例分别为0、29．2％、34．5％，铁沉积比例分别为11.1％、52．1％、25．9％，AIH组与其他两组比较，P值均〈0．05，差异均有统计学意义。结论DILI患者与AIH患者在生物化学、免疫学、肝组织病理学表现上存在差异。AIH患者的界面炎症、汇管区炎症、纤维化程度比DILI患者严重，铁沉积、蜡质样沉积在DILI患者中明显增多。

Objective To investigate the differences and similarities between drug-induced liver injury （DILI） and autoimmune hepatitis （AIH） in serum biochemical parameters and liver pathology, and to provide some thoughts for clinical diagnosis and differentiation of these two diseases. Methods A retrospective analysis was performed for the biochemical, immtmological, autoantibody, and liver pathological data of 106 DILI patients and 63 AIH patients who were hospitalized, diagnosed, and treated in our hospital from January 2012 to October 2014. The patients＇ general data, biochemical parameters, immunological data, Ishak score, and qualitative changes in liver tissue were analyzed and compared. The Kruskal-Wallis test was used for comparison of nonparametric data between multiple groups, the Nemenyi test was used for comparison of nonparametric data between any two groups, the Wilcoxon rank sum test was used for comparison oflshak scores, and the chi-square test was used for comparison of constituent ratio of categorical data. Results There were significant differences between AIH group and DILI hepatocyte injury group/ mixed-type DILI group in the following serum biochemical parameters： alanine aminotransferase （187.2 U/L vs 1 326.5 U/L and 455.6, P 〈 0.05）, aspartate aminotransferase （172.2 U/L vs 759.5 U/L and 349.5 U/L, P 〈 0.05）, a/kaline phosphatase （209.3 U/L vs 157.3 U/L and 169.4 U/L, .P 〈 0.05）, gamma-glutamyl transferase （254.8 U/L vs 176.5 U/L and 170.5 U/L, P 〈 0.05）, total bilimbin （37.2 μmol/L vs 95.8 μmol/L and 52.6 μmol/L, P 〈 0.05）, serum iron （18.9 μmol/L vs 36.2 μmol/L and 23.9 μmol/L, P 〈 0.05）, serum ferritin （122.5 μmol/L vs 410.4 μmol/L and 186.5 μmol/L, P 〈 0.05）, immunoglobulin G （18.4 g/L vs 12.6 g/L and 12.3 g/L, P 〈 0.05）, and immtmoglobulin M （1.8 g/L vs 1.3 g/L and 1.1 g/L, P 〈 0.05）. There were also significant differences between AIH group and DILI hepatocyte injury group/mixed-type DILI group in the Ishak score for interface inflammation （2.2±0.8 vs 1.3±0.7 and 1.3±0.6, P 〈 0.05）, Ishak score for portal inflammation （2.3±0.9 vs 1.5±0.7 and 1.4±0.8, P 〈 0.05）, and fibrosis score （2.8±1.1 vs 1.5±0.7 and 1.3±0.7, P 〈 0.05）. There were significant differences between AIH group and DILl hepatocyte injury group/mixed-type DILl group in the proportion of wax-like deposition （0 vs 29.2% and 34.5%, P 〈0.05） and proportion of iron deposition （11.1% vs 52.1% and 25.9%, P 〈 0.05）. Conclusion There are differences in biochemistry, immunology, and liver histology between DILl and AIH patients. AIH patients have more serious interface inflammation and portal inflammation and a higher fibrosis degree compared with DILl patients, while DILl patients have greater proportions of wax-like deposition and iron deposition compared with AIH patients.