肝移植术后迟发型急性排斥反应的发生和治疗

Late acute rejection following orthoptic liver transplantation

目的探讨肝移植术后迟发型急性排斥反应（lateacuterejection，LAR）的发生率、处理和预后。方法回顾性分析我科2004年8月至2006年8月收治的15例迟发型急性排斥反应（肝移植术6个月后发生的急性排斥反应）患者的临床资料。结果15例LAR发生在术后6．6—27个月，平均（14．7±7．5）个月。其中男14例，女1例。年龄32～66岁，平均年龄（49．5±12．7）岁。原发疾病为重症肝炎或肝功能衰竭者8例，占53．3％（8／15）；发生于血型不合移植者2例，免疫抑制治疗方案为单一普乐可复（FK506）治疗8例，单一环孢素A（CsA）治疗3例，已经停用激素13例，占86．7％。属于免疫抑制剂量不足者共10例，占66．7％。免疫抑制剂浓度正常范围者5例。按Banff分级标准排斥反应的程度为轻度者9例，中度6例，无重度排斥反应发生。治疗方法均首先加强或调整免疫抑制治疗，包括提高药物浓度、FK506／CsA转换、联合其他免疫抑制剂和激素冲击治疗，3例患者需长期口服激素。总的治愈率为80％，3例患者逐渐出现缺血型胆道病变，其中1例行再移植后死亡。结论迟发型急性排斥反应是肝移植术后常见但预后较好的并发症之一，免疫抑制不足是其发生的主要原因，及时地加强免疫抑制治疗可逆转排斥反应。

Objective To evaluate the incidence, treatment and outcome of late acute rejection （LAR） following liver transplantation. Methods A retrospective analysis was made on 15 cases suffering from LAR after liver transplantation from Aug 2004 to Aug 2006. LAR was defined as biopsy proven rejection occurring 〉 6 months post-transplant. Results LAR was diagnosed in 15 patients with a mean observation period of 14. 7 ±7. 5 months （6. 6 -27 months）, among them 14 were male and 1 was female with a mean age of 49. 5 ± 12. 7 years. Indications for LT were： acute or chronic liver failure due to hepatitis B infection （ n = 8 ） , hepatocellular carcinoma （ n = 4 ） , posthepatitic cirrhosis （ n = 2 ） , alcoholic cirrhosis （ n = 1 ）. Immunosuppressive protocol was tacrolimus （ FK506 ） monotherapy （ n = 8 ）, cyclosporine （ CsA ） monotherapy （n = 3）,FK506 combined with mycophenolate mofetil （MMF）（ n = 2）, FK506 combined with steroid （n = 1 ） , CsA combined with steroid （n = 1 ）. Steroid had been withdrawn before the rejection developed in 13 patients（86. 7% ）. Serum immunosuppressant level was within normal range in 5 out of the 15 patients. According to Banff grade 9 were mild and 6 were moderate. Management included increasing sennn level of the immunosuppressive drugs or a switch from cyclosporine to tacrolimus in those not responding to reestablished level of immunosuppression. Three patients were treated with intravenous steroid bolus and were on maintenance dose of steroid （ methylprednisolone, 5 - 10mg per day）. The overall patient survival was 80%. Three patients have progressed to ischemic-type biliary lesions（ITBLs） at the time of last follow-up and 1 died. Conclusions LAR is a common occurrence but has a benign outcome following liver transplantation. Prompt intervention to correct inadequate immunosuppression is essential for the salvage of this complication.