Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada.
Center for Liver Research & NIHR Birmingham BRC, University of Birmingham & University Hospital Birmingham NHS Foundation Trust, Institute of Immunology and Immunotherapy, University of Birmingham, UK.
J Hepatol. 2022 Jul;77(1):84-97. doi: 10.1016/j.jhep.2022.01.022. Epub 2022 Feb 8.
BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.
We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.
AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001).
Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH.
Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.
自身免疫性肝炎（AIH）患者在肝移植（LT）后可能会复发，尽管复发对患者和移植物存活率的影响尚未得到很好的描述。我们评估了一个大型的国际多中心队列，以确定与 AIH 复发相关的概率和危险因素，以及疾病复发与患者和移植物存活率之间的关系。
我们纳入了 736 名 AIH 患者（77%为女性，平均年龄 42±1 岁），他们于 1987 年 1 月至 2020 年 6 月期间在北美、南美、欧洲和亚洲的 33 个中心接受 LT。分析 LT 前后的临床数据、LT 后 12 个月内的生化数据以及 LT 后的免疫抑制数据，以根据组织学诊断确定 AIH 复发风险较高的患者。
5 年后，20%的患者出现 AIH 复发，10 年后，31%的患者出现 AIH 复发。LT 时年龄≤42 岁（风险比[HR]3.15；95%置信区间[CI]1.22-8.16；p=0.02）、LT 后使用霉酚酸酯（HR 3.06；95%CI 1.39-6.73；p=0.005）、供体和受体性别不匹配（HR 2.57；95%CI 1.39-4.76；p=0.003）和 LT 前 IgG 水平较高（HR 1.04；95%CI 1.01-1.06；p=0.004）与 AIH 复发风险增加相关。在多变量 Cox 回归中，复发性 AIH（作为时变协变量）与移植物丢失（HR 10.79，95%CI 5.37-21.66，p<0.001）和死亡（HR 2.53，95%CI 1.48-4.33，p=0.001）显著相关。
LT 后 AIH 的复发较为常见，与 LT 时年龄较小、LT 后使用霉酚酸酯、性别不匹配和 LT 前 IgG 水平较高有关。我们证明了 AIH 患者疾病复发与移植物和总体存活率受损之间存在关联，这突显了需要努力更好地描述、预防和治疗复发性 AIH。
LT 后自身免疫性肝炎（AIH）的复发较为常见，与某些受者特征和免疫抑制药物的使用类型有关。复发性 AIH 会对 LT 后的结果产生负面影响。因此，需要采取改进措施来预防和治疗这种情况。
