药物诱导自身免疫性肝炎与特发性自身免疫性肝炎在血清学及组织学方面的鉴别

发布时间：2019-03-01 13:41

【摘要】：背景和目的:药物诱导自身免疫性肝炎的诊断及其与特发性自身免疫性肝炎的鉴别面临挑战。本研究旨在血清学、组织学、免疫细胞学综合分析中发现药物诱导自身免疫性肝炎区别于自身免疫性肝炎的标志物。方法:该研究纳入15名药物诱导自身免疫性肝炎患者及24名特发性自身免疫性肝炎病人,所有患者均在我院行肝脏穿刺活检。根据1999年自身免疫性肝炎国际评分系统吻合药物诱导自身免疫性肝炎和自身免疫性肝炎情况作为诊断依据。重叠综合症,病毒性肝炎和代谢性肝病患者被排除在外。收集所有患者的临床资料及实验室检查结果。HE染色观察其组织学改变。通过对连续肝组织切片内CD4~+Foxp3+CD25~(+/-)T调节细胞的单/双免疫组织化学染色,以此对细胞表型识别区分。使用流式细胞仪测定外周血中CD4~+Foxp3+CD25~(+/-)调节性T细胞百分比。对所有患者的治疗及预后进行随访。结果:药物诱导自身免疫性肝炎患者均为女性,平均年龄为52岁(44~57岁),本组患者病发诱因大部分与中药有关。临床表现主要为右上腹部不适、恶心、呕吐、厌食等,个别患者可伴随有肝外的表现,如关节炎、过敏性皮炎等。血清ALT、AST、球蛋白及免疫球蛋白均高于正常。与特发性自身免疫性肝炎相比,药物诱导自身免疫性肝炎的AST、ALT升高的水平更高,肝小叶内的炎症浸润更明显,3区坏死更多见,并且肝小叶内CD4~+Foxp3+CD25-T调节细胞数量更多(P0.01,P0.05,P0.05,和P0.01)。并且,药物诱导自身免疫性肝炎中,肝小叶内的炎症浸润程度与AST/ALT升高的水平或者肝小叶内CD4~+Foxp3+CD25-调节性T细胞数量成正相关(P0.05,P0.01,P0.01)。最后,肝小叶内嗜酸性细胞和淋巴细胞浸润以及汇管区胆管增生在药物诱导自身免疫性肝炎中比特发性自身免疫性肝炎更常见(P均0.05)。然而,外周血中CD4~+Fosp3+CD25~(+/-)调节性T细胞在药物诱导自身免疫性肝炎、自身免疫性肝炎及健康对照组中并无显著差异。结论:药物诱导自身免疫性肝炎与特发性自身免疫性肝炎病人中存在的一些鉴别点,这些要点对于两种疾病的鉴别有临床意义,可以在疾病早期阶段协助诊断。
[Abstract]:Background & objective: the diagnosis of drug-induced autoimmune hepatitis and its differentiation from idiopathic autoimmune hepatitis are challenging. The aim of this study is to find out that drug-induced autoimmune hepatitis is different from autoimmune hepatitis in comprehensive analysis of serology, histology and immunologic cytology. Methods: this study included 15 patients with drug-induced autoimmune hepatitis and 24 patients with idiopathic autoimmune hepatitis. All patients underwent liver biopsy in our hospital. According to the international scoring system for autoimmune hepatitis in 1999, autoimmune hepatitis and autoimmune hepatitis induced by drugs were used as diagnostic basis. Patients with overlap syndrome, viral hepatitis and metabolic liver disease are excluded. The clinical data and laboratory results of all patients were collected. The histological changes were observed by HE staining. Single / double immunohistochemical staining of CD4~ Foxp3 CD25~ (/ -) T-regulated cells in continuous sections of liver tissue was used to identify and distinguish the phenotypes of the cells. The percentage of CD4~ Foxp3 CD25~ (/ -) regulatory T cells in peripheral blood was measured by flow cytometry. All patients were followed up for treatment and prognosis. Results: all patients with drug-induced autoimmune hepatitis were female with an average age of 52 years (44-57 years). Most of the patients were associated with traditional Chinese medicine. The main clinical manifestations are right upper abdominal discomfort, nausea, vomiting, anorexia, etc. Individual patients may be accompanied by extrahepatic manifestations, such as arthritis, allergic dermatitis and so on. Serum ALT,AST, globulin and immunoglobulin were higher than normal. Compared with idiopathic autoimmune hepatitis, the level of AST,ALT in drug-induced autoimmune hepatitis was higher than that in idiopathic autoimmune hepatitis, the inflammatory infiltration in hepatic lobules was more obvious, and necrosis in area 3 was more common. And the number of CD4~ Foxp3 CD25-T-regulated cells in hepatic lobules was higher (P 0.01, P 0.05, and P0.01). In addition, the degree of inflammatory infiltration in hepatic lobules was positively correlated with the increased level of AST/ALT or the number of CD4~ Foxp3 CD25- regulatory T cells in the lobules in drug-induced autoimmune hepatitis (P0.05, P0.01, P0.01). Finally, the infiltration of eosinophils, lymphocytes and bile duct proliferation in hepatic lobules were more common in drug-induced autoimmune hepatitis than in idiopathic autoimmune hepatitis (P 0.05). However, there was no significant difference in CD4~ Fosp3 CD25~ (/ -) regulatory T cells between drug-induced autoimmune hepatitis, autoimmune hepatitis and healthy controls. Conclusion: there are some distinguishing points in patients with autoimmune hepatitis induced by drugs and idiopathic autoimmune hepatitis. These points are of clinical significance for the differential diagnosis of the two diseases and can assist in the diagnosis of the two diseases in the early stage of the disease.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575.1

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