Vergani D, Mieli-Vergani G
Department of Immunology, King's College School of Medicine and Dentistry, London, UK.
Ann Ital Med Int. 1996 Apr-Jun;11(2):119-24.
Autoimmune hepatitis is an inflammatory liver disease in which the immune system is believed to orchestrate an immune attack onto the liver cell. Current knowledge suggests that both T helper 1 (TH1) and TH2 programmes are involved in the generation of the liver damage. Release of TH2 cytokines leads to the production of autoantibodies to the hepatocyte membrane that recruit killer cells. TH1 cytokines induce macrophage activation which contributes to hepatocyte destruction. Patients commonly possess the "autoimmune" HLA A1/B8/DR3 haplotype and a silent gene at the C4A locus with consequent partial deficiency of the complement component C4. Two main types of autoimmune hepatitis are recognised according to the presence of circulating non-organ specific autoantibodies. Patients with smooth muscle antibody and/or antinuclear antibody may be adults or children, while patients with antiliver kidney microsomal type 1 (LKM1) antibody are usually children or very young adults. In both types there is a preponderance of females. LKM1 antibody is also present in a proportion of adult patients, mainly male, with chronic hepatitis C virus infection. This observation originally led to the suggestion that hepatitis C virus may be the cause of this form of autoimmune hepatitis, but several studies have shown that the epitopes target of the LKM1 antibody in autoimmune hepatitis and chronic hepatitis C virus infection differ. Although autoimmune hepatitis responds satisfactorily to immunosuppression in the short term, progression to cirrhosis is frequent. It is hoped that ongoing research will provide a better understanding of the pathogenic mechanisms of liver damage leading to a more effective and specific mode of treatment.
自身免疫性肝炎是一种炎症性肝病,据信免疫系统会对肝细胞发动免疫攻击。目前的认识表明,辅助性T细胞1(TH1)和TH2程序都参与了肝损伤的发生。TH2细胞因子的释放导致产生针对肝细胞膜的自身抗体,进而募集杀伤细胞。TH1细胞因子诱导巨噬细胞活化,这有助于肝细胞破坏。患者通常具有“自身免疫性”HLA A1/B8/DR3单倍型以及C4A基因座处的沉默基因,从而导致补体成分C4部分缺乏。根据循环中存在的非器官特异性自身抗体,可识别出两种主要类型的自身免疫性肝炎。平滑肌抗体和/或抗核抗体阳性的患者可能是成人或儿童,而抗1型肝肾微粒体(LKM1)抗体阳性的患者通常是儿童或非常年轻的成年人。两种类型中女性均占多数。一部分慢性丙型肝炎病毒感染的成年患者(主要为男性)也存在LKM1抗体。这一观察结果最初提示丙型肝炎病毒可能是这种自身免疫性肝炎的病因,但多项研究表明,自身免疫性肝炎和慢性丙型肝炎病毒感染中LKM1抗体的表位靶点不同。尽管自身免疫性肝炎在短期内对免疫抑制治疗反应良好,但经常会进展为肝硬化。希望正在进行的研究能够更好地理解肝损伤的致病机制,从而带来更有效、更具特异性的治疗方式。