Gibelli Nelson E, Tannuri Uenis, Mello Evandro S, Cançado Eduardo R, Santos Maria M, Ayoub Ali A, Maksoud-Filho João G, Velhote Manoel C P, Silva Marcos M, Pinho-Apezzato Maria L, Maksoud João G
Liver Transplantation Unit, Children Institute, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil.
Pediatr Transplant. 2006 May;10(3):371-6. doi: 10.1111/j.1399-3046.2005.00470.x.
Over a 15-yr period of observation, among the 205 children who underwent liver transplantations, one of them developed a particular type of late graft dysfunction with clinical and histological similarity to autoimmune hepatitis. The patient had alpha1-antitrypsin deficiency and did not previously have autoimmune hepatitis or any other autoimmune disease before transplantation. Infectious and surgical complications were excluded. After repeated episodes of unexplained fluctuations of liver function tests and liver biopsies demonstrating reactive or a biliary pattern, without any corresponding alteration of percutaneous cholangiography, a liver-biopsy sample taken 4 yr after the transplant showed active chronic hepatitis progressing to cirrhosis, portal lymphocyte aggregates, and a large number of plasma cells. At that time, autoantibodies (gastric parietal cell antibody, liver-kidney microsomal antibody, and anti-hepatic cytosol) were positive and serum IgG levels were high. Based on these findings of autoimmune disease, a diagnosis of 'de novo autoimmune hepatitis' was made. The treatment consisted of reducing the dose of cyclosporine, reintroduction of corticosteroids, and addition of mycophenolate mofetil. After 19 months of treatment, a new liver-biopsy sample showed marked reduction of portal and lobular inflammatory infiltrate, with regression of fibrosis and of the architectural disruption. At that time, serum autoantibodies became negative. The last liver-biopsy sample showed inactive cirrhosis and disappearance of interface hepatitis and of plasma cell infiltrate. Presently, 9 yr after the transplantation, the patient is doing well, with normal liver function tests and no evidence of cirrhosis. Her immunosuppressive therapy consists of tacrolimus, mycophenolate mofetil, and prednisolone. In conclusion, the present case demonstrates that de novo autoimmune hepatitis can appear in liver-transplant patients despite appropriate anti-rejection immunosuppression, and triple therapy with tacrolimus, mycophenolate mofetil, and prednisolone could sustain the graft and prevent retransplantation.
在15年的观察期内，205名接受肝移植的儿童中，有1名出现了一种特殊类型的晚期移植物功能障碍，其临床和组织学表现与自身免疫性肝炎相似。该患者患有α1抗胰蛋白酶缺乏症，移植前未曾患自身免疫性肝炎或任何其他自身免疫性疾病。排除了感染和手术并发症。在肝功能检查反复出现无法解释的波动且肝活检显示为反应性或胆汁型，而经皮胆管造影无任何相应改变后，移植后4年采集的肝活检样本显示活动性慢性肝炎进展为肝硬化、门静脉淋巴细胞聚集以及大量浆细胞。当时，自身抗体（胃壁细胞抗体、肝肾微粒体抗体和抗肝细胞溶质抗体）呈阳性，血清IgG水平升高。基于这些自身免疫性疾病的发现，做出了“新发自身免疫性肝炎”的诊断。治疗措施包括降低环孢素剂量、重新使用皮质类固醇以及加用霉酚酸酯。经过19个月的治疗，新的肝活检样本显示门静脉和小叶炎性浸润明显减少，纤维化和结构破坏消退。当时，血清自身抗体转阴。最后一次肝活检样本显示为静止性肝硬化，界面性肝炎和浆细胞浸润消失。目前，移植后9年，患者情况良好，肝功能检查正常，无肝硬化迹象。她的免疫抑制治疗包括他克莫司、霉酚酸酯和泼尼松龙。总之，本病例表明，尽管进行了适当的抗排斥免疫抑制，新发自身免疫性肝炎仍可出现在肝移植患者中，他克莫司、霉酚酸酯和泼尼松龙三联疗法可维持移植物并防止再次移植。
