Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom; Organ Donation and Transplantation, National Health Service Blood and Transplant (NHSBT), Bristol, United Kingdom.
Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Organ Donation and Transplantation, National Health Service Blood and Transplant (NHSBT), Bristol, United Kingdom.
J Hepatol. 2014 Jan;60(1):210-23. doi: 10.1016/j.jhep.2013.09.020. Epub 2013 Sep 29.
Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune process is not clear. In this manuscript, we review novel findings about disease processes and mechanisms that lead to autoimmunity in the liver and their possible involvement in the immune response vs. the graft after LT.
原发性胆汁性肝硬化 (PBC)、原发性硬化性胆管炎 (PSC) 和自身免疫性肝炎 (AIH) 代表三种主要的自身免疫性肝病 (AILD)。PBC、PSC 和 AIH 都是复杂的疾病，因为它们是由多个基因与尚未确定的环境因素共同作用的结果。最近的全基因组关联研究已经确定了许多 PBC 和 PSC 的风险位点，这些位点的宿主基因涉及先天或获得性免疫反应。这些位点可能为 AILD 的免疫发病机制提供线索。此外，许多 PBC 和 PSC 的重要风险位点也是其他自身免疫性疾病（如 1 型糖尿病、多发性硬化症和类风湿关节炎）的风险位点，这表明存在共同的遗传基础和可能相似的分子途径用于多种自身免疫性疾病。这三种疾病都没有治愈方法，而且相当数量的患者最终会发展为需要肝移植 (LT) 的终末期肝病。在这种情况下，LT 的整体预后良好，目前患者和移植物的 5 年生存率超过 80%。适应证与其他慢性肝病相同，尽管最近的数据表明，尽管移植后乏力会有所改善，但效果是适度且多变的，因此乏力本身不是适应证。相反，瘙痒会迅速得到缓解。胆管癌除外，在严格的选择标准下，由于复发风险高，不适合 LT。三种情况都可能在移植后复发，并与急性细胞和慢性胆管缺失排斥反应的风险增加相关。同种异体免疫和自身免疫反应之间可能存在相互作用，从而使彼此持续存在。在非自身免疫性疾病的患者接受 LT 后，对自身或同种抗原的免疫反应在肝脏中得到很好的识别，有时称为“新发自身免疫性肝炎”。这是排斥反应的一部分还是自身免疫过程尚不清楚。在这篇手稿中，我们回顾了导致肝脏自身免疫的疾病过程和机制的新发现，以及它们在 LT 后对免疫反应与移植物的可能参与。
