自體免疫性肝炎之最新進展

廣義的自體免疫性肝炎是一種慢性發炎性肝臟病變，包括慢性活動性肝炎、原發性膽汁鬱積性肝硬化和原發性硬化性膽管炎以及重疊症候群等。其致病成因未明，血中會出現自體抗體以及血清球蛋白增高爲其特徵。組織病理學表徵爲初期門脈區域單核細胞浸潤，逐漸延伸至肝實質區，造成周邊肝細胞碎片狀壞死，隨著病程進展，從門脈區延伸至中心靜脈區橋連壞死，最後導致肝硬化。免疫組織化學染色顯示，早期損壞的膽管通常會被CD4+T淋巴細胞浸潤，導致慢性發炎性病變，接著由CD8+T淋巴細胞進一步浸潤破壞，導致膽汁鬱積性肝硬化。對於自體免疫性肝炎細胞損傷免疫作用的機轉，包括T淋巴細胞介導細胞毒殺作用以及抗體介導細胞毒殺作用ADCC（Antibody dependent cell-mediated cytotoxicity），多數學者認爲以ADCC作用爲主。血清學診斷，第一型（典型）自體免疫性肝炎的循環抗體中，以抗核抗體、抗平滑肌抗體，及抗肌動蛋白抗體爲最常見。抗粒腺體抗體與抗核抗體常出現於原發性膽汁鬱積性肝硬化。第二型自體免疫性肝炎，會出現抗第一型肝－腎微粒體抗體以及抗第一號肝臟細胞溶質抗體爲特徵。關於分子細胞毒性、細胞激素，以及免疫調控方面的研究報告指出，自體免疫性肝炎其抑制性T細胞功能的缺陷，可因類固醇的治療而得到改善。雖然自體免疫性肝炎治療失敗率只有20%左右，但是對於長期慢性病程以及具有HLA-B8或DR3基因表現型的患者而言，具有發展成肝硬化，甚至接受肝臟移植的高危險性。不論是T細胞疫苗、阻斷胜肽，或者單株抗體的治療，在移植前後可能效益如何，都須視未來的研究成果而定，而且更需視是否能對其致病成因及免疫機轉有更透徹的瞭解與認識。

關鍵字

自體免疫性肝炎；原發性膽汁鬱積性肝硬化；原發性硬化性膽管炎；抗粒線體抗體；抗平滑肌抗體

並列摘要

Autoimmune hepatitis (AIH) is a chronic necroinflammatory liver disorder of unknown cause associated with circulating autoantibodies and a high serum globulin level. It is important to distinguish autoimmune hepatitis from other forms of liver disease because a high percentage of cases respond to antiinflammatory and immunosuppressive treatment. The characteristic histological lesion in the early stages is the presence of granulomas in the portal tracts with destruction of middle-sized bile ducts. The damaged ducts are surrounded and infiltrated typically by CD4+ T lymphocytes, with a further surrounding infiltrate of CD8+ T cells at the periphery of the portal tract, the site at which cirrhosis develops eventually. The pathogenesis of bile duct damage in AIH is unclear. Bile ducts in AIH patients express increased densities of adhesion molecules, MHC class Ⅱ antigens, IL-2 receptor and pyruvate dehydrogenase compared with normal ducts, and so represent potential targets for the infiltrating activated T cells. There are similarities between AIH and chronic graft-versus-host disease (GVHD), which is known to be mediated by cytotoxic T cells. The circulating autoantibodies commonly present in Type I (classic) autoimmune hepatitis are antinuclear, anti-smooth-muscle, antiactin antibodies, and anti-asialoglycoprotein receptor. Type Ⅱ AIH is characterized by the presence of circulating antibodies against liver-kidney microsome type 1 (anti-LKM-1) and of anti-liver cytosol antibodies. Early diagnosis with appropriate management can prolong survival, improve the quality of life, and defer liver transplantation. Liver transplantation remains the only effective therapy for patients with end stage PBC. Results are good, with 5-year survival in excess of 80%. Whether T-cell vaccines, blocking peptides, or monoclonal antibodies may be beneficial before or after transplantation depends on further investigation and perhaps a better understanding of the pathogenesis of autoimmune hepatitis.

並列關鍵字

Autoimmune hepatitis ； AIH ； Primary biliary cirrhosis ； PBC ； Primary sclerosing cholangitis ； PSC ； Anti-mitochondrial antibodies ； AMA ； Anti-smooth muscle antibodies ； ASMA

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自體免疫性肝炎之最新進展

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