Salcedo Magdalena, Rodríguez-Mahou Margarita, Rodríguez-Sainz Carmen, Rincón Diego, Alvarez Emilio, Vicario Jose Luis, Catalina Maria-Vega, Matilla Ana, Ripoll Cristina, Clemente Gerardo, Bañares Rafael
Liver Transplantation Unit, Gastroenterology and Hepatology Division (CIBERHED), Madrid, Spain.
Liver Transpl. 2009 May;15(5):530-9. doi: 10.1002/lt.21721.
De novo autoimmune hepatitis (de novo AIH) is a rare form of graft dysfunction that develops after liver transplantation (LT) in patients transplanted for conditions other than autoimmune disorders. Although characterized by biochemical, serological, and histological features of AIH, de novo AIH is sometimes associated with atypical serum autoantibodies, many of which are directed against glutathione S-transferase T1 (anti-GSTT1). GSTT1 donor/recipient genotype mismatch has been suggested as a necessary condition for the appearance of autoantibodies and de novo AIH. However, clinically evident disease is not observed in all patients with anti-GSTT1 antibodies. We examined the incidence of de novo AIH and its conditioning (risk) factors in patients with anti-GSTT1 antibodies. Anti-GSTT1 autoantibodies were detected in 29 of 419 [6.9%; 95% confidence interval (CI), 4.9-9.8] consecutive adult LT recipients with donor/recipient GSTT1 mismatch. Twenty of 27 assessable patients (74%) developed de novo AIH after a median follow-up of 26 months (95% CI, 19.2-32.8). The probability of de novo AIH was 11%, 44%, and 60% 12, 24, and 36 months after LT, respectively. No relationship emerged between de novo AIH and recipient gender, donor and recipient age, rejection episodes, immunosuppressive regime, allelic GSTT1 expression, human leukocyte antigen distribution, or cytomegalovirus infection. Multivariate analysis identified male donor [hazard ratio (HR), 3.3; 95% CI, 1.18-9.26; P = 0.018], nonalcoholic etiology (HR, 4.67; 95% CI, 1.64-13.3; P = 0.002), and high anti-GSTT1 titer (HR, 2.98; 95% CI, 1.04-8.57; P = 0.035) as independent predictors of de novo AIH. Most patients with anti-GSTT1 antibodies and donor/recipient GSTT1 mismatch developed clinically evident de novo AIH after LT. The risk of developing the disease was increased by male donor gender, nonalcoholic etiology of original liver disease, and a high anti-GSTT1 titer.
新发自身免疫性肝炎（de novo AIH）是肝移植（LT）后出现的一种罕见的移植物功能障碍形式，发生于因非自身免疫性疾病接受移植的患者。尽管新发自身免疫性肝炎具有自身免疫性肝炎的生化、血清学和组织学特征，但有时与非典型血清自身抗体相关，其中许多抗体针对谷胱甘肽S-转移酶T1（抗GSTT1）。GSTT1供体/受体基因型不匹配被认为是自身抗体和新发自身免疫性肝炎出现的必要条件。然而，并非所有抗GSTT1抗体阳性的患者都会出现临床明显的疾病。我们研究了抗GSTT1抗体阳性患者中新发自身免疫性肝炎的发病率及其相关（风险）因素。在419例连续的成年LT受者中，29例（6.9%；95%置信区间[CI]，4.9 - 9.8）供体/受体GSTT1不匹配的患者检测到抗GSTT1自身抗体。在27例可评估的患者中，20例（74%）在中位随访26个月（95% CI，19.2 - 32.8）后发生了新发自身免疫性肝炎。LT后12、24和36个月时，新发自身免疫性肝炎的发生率分别为11%、44%和60%。新发自身免疫性肝炎与受者性别、供体和受者年龄、排斥反应、免疫抑制方案、等位基因GSTT1表达、人类白细胞抗原分布或巨细胞病毒感染之间均无关联。多因素分析确定男性供体[风险比（HR），3.3；95% CI，1.18 - 9.26；P = 0.018]、非酒精性病因（HR，4.67；95% CI，1.64 - 13.3；P = 0.002）和高抗GSTT1滴度（HR，2.98；95% CI，1.04 - 8.57；P = 0.035）是新发自身免疫性肝炎的独立预测因素。大多数抗GSTT1抗体阳性且供体/受体GSTT1不匹配的患者在LT后出现了临床明显的新发自身免疫性肝炎。男性供体性别、原发病的非酒精性病因以及高抗GSTT1滴度会增加患该病的风险。
