Heneghan M A, Portmann B C, Norris S M, Williams R, Muiesan P, Rela M, Heaton N D, O'Grady J G
Institute of Liver Studies, King's College Hospital, Denmark Hill, London, England.
Hepatology. 2001 Sep;34(3):464-70. doi: 10.1053/jhep.2001.26756.
In children, a type of graft dysfunction associated with autoimmune features has been described. We have identified 7 adult liver-transplant (LT) recipients from a series of over 1,000 consecutive transplant recipients who presented between 0.3 years and 7.2 years following transplantation with characteristic symptoms, autoantibody profiles, and histologic findings of autoimmune disease. The indications for transplantation were Ecstasy overdose, alcohol-related cirrhosis, primary sclerosing cholangitis (PSC) (2), primary biliary cirrhosis (PBC), hepatitis C cirrhosis, and cryptogenic cirrhosis. Two patterns of de novo autoantibody development were noted; anti-liver-kidney-microsome (LKM) antibody development at high titer in association with an aspartate transaminase (AST) > 500 and antinuclear (ANA) and antismooth muscle (AMA) antibody development at titers >1/80 with lower AST levels. All cases had elevated IgG. Liver biopsies showed changes of an autoimmune-type hepatitis with portal and periportal hepatitis in association with a marked infiltrate of plasma cells, lymphocytes, and bridging collapse. Two patients lost their grafts because of the disease. Patients were treated with reintroduction of steroids and azathioprine in cases in which it had been withdrawn. Major histocompatibility class I and II mismatching did not incur risk. Eight of 12 liver allografts were acquired from either DRB0301- or DRB0401-positive donors, and 4 recipients were DRB*0301-positive. This series illustrates that both symptoms and histologic findings of graft dysfunction compatible with autoimmune hepatitis (AIH) exist in adult LT recipients. Graft loss may be a consequence. This entity may represent a specific type of rejection that should currently be classified as "graft dysfunction mimicking autoimmune hepatitis."
在儿童中，已描述了一种与自身免疫特征相关的移植物功能障碍类型。我们从一系列超过1000例连续的移植受者中识别出7例成人肝移植（LT）受者，他们在移植后0.3年至7.2年出现了自身免疫性疾病的特征性症状、自身抗体谱和组织学表现。移植的适应证为摇头丸过量、酒精性肝硬化、原发性硬化性胆管炎（PSC）（2例）、原发性胆汁性肝硬化（PBC）、丙型肝炎肝硬化和隐源性肝硬化。注意到两种新发自身抗体产生模式；高滴度抗肝肾微粒体（LKM）抗体产生伴天冬氨酸转氨酶（AST）>500，以及抗核（ANA）和抗平滑肌（AMA）抗体滴度>1/80且AST水平较低。所有病例的IgG均升高。肝活检显示自身免疫性肝炎样改变，伴有门脉性和门脉周围肝炎，伴有浆细胞、淋巴细胞明显浸润和桥接坏死。2例患者因该病失去了移植物。在停用类固醇和硫唑嘌呤的病例中，重新使用这些药物进行治疗。主要组织相容性复合体I类和II类不匹配未带来风险。12例肝同种异体移植中有8例来自DRB0301或DRB0401阳性供体，4例受者为DRB*0301阳性。该系列表明，成人LT受者中存在与自身免疫性肝炎（AIH）相符的移植物功能障碍的症状和组织学表现。移植物丢失可能是其后果。该实体可能代表一种特定类型的排斥反应，目前应归类为“模仿自身免疫性肝炎的移植物功能障碍”。
