Jain Ashok, Mazariegos George, Pokharna Renu, Parizhskaya Maria, Kashyap Randeep, Kosmach-Park Beverly, Smith Amy, Fung John J, Reyes Jorge
Thomas E. Starzl Transplantation Institute, Department of Surgery, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.
Transplantation. 2003 Apr 15;75(7):1020-5. doi: 10.1097/01.TP.0000056168.79903.20.
Although the outcome of liver transplantation has improved significantly during the past two decades, graft loss caused by chronic rejection after liver transplantation still occurs in 2% to 20% of recipients. The overall incidence of chronic rejection is also reported to be low in adult recipients, and risk factors have been identified. Chronic rejection is associated with the inability to maintain baseline immunosuppression. Additionally, the diagnoses of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, hepatitis B virus, and hepatitis C virus, common indications for liver transplantation in adults, are associated with a higher incidence of chronic rejection. Fortunately, these diagnoses are rarely seen in children. Little is known about chronic rejection in long-term pediatric liver transplant survivors. The purpose of this longitudinal study was to examine the incidence of biopsy-proven chronic rejection in long-term survivors of primary pediatric liver transplantation under tacrolimus-based immunosuppression.
From October 1989 to December 1992, 166 children (boys=95, girls=71; mean age=5.0+/-2.9 years) received a primary liver transplant. These patients were followed until March 2000 with a mean follow-up of 9+/-0.8 (range, 7.4-10.4) years. All liver biopsy specimens and explanted grafts were evaluated for evidence of chronic rejection using the International Banff Criteria.
The mortality rate during the follow-up period was 15% (n=25). Retransplantation was required in 11% (n=18) of recipients. Actuarial patient and graft survival rates at 10 years were 84.9% and 80.1%, respectively. There were 535 liver biopsy samples available for evaluation, including the 18 explanted allografts. Biopsy specimens of three other functioning allografts showed evidence of chronic rejection. Immunosuppression had been discontinued or drastically reduced in these recipients because of life-threatening infections, noncompliance, or both. On restoring baseline immunosuppression, all three children had normalized liver function and the allografts were maintained; the liver transplant patients who are alive currently have normal liver functions.
The findings of this study suggest that chronic rejection does not occur in pediatric liver transplant recipients receiving tacrolimus-based immunosuppression, provided baseline immunosuppression is maintained.
尽管在过去二十年中肝移植的结果有了显著改善，但肝移植后由慢性排斥反应导致的移植物丢失仍发生在2%至20%的受者中。据报道，成人受者中慢性排斥反应的总体发生率也较低，并且已经确定了危险因素。慢性排斥反应与无法维持基线免疫抑制有关。此外，原发性胆汁性肝硬化、原发性硬化性胆管炎、自身免疫性肝炎、乙型肝炎病毒和丙型肝炎病毒这些成人肝移植的常见适应证，与慢性排斥反应的较高发生率相关。幸运的是，这些诊断在儿童中很少见。关于长期小儿肝移植存活者的慢性排斥反应知之甚少。这项纵向研究的目的是在基于他克莫司的免疫抑制下，检查原发性小儿肝移植长期存活者中经活检证实的慢性排斥反应的发生率。
从1989年10月至1992年12月，166名儿童（男95名，女71名；平均年龄5.0±2.9岁）接受了原发性肝移植。对这些患者进行随访直至2000年3月，平均随访时间为9±0.8（范围7.4 - 10.4）年。使用国际班夫标准对所有肝活检标本和切除的移植物进行慢性排斥反应证据的评估。
随访期间的死亡率为15%（n = 25）。11%（n = 18）的受者需要再次移植。10年时的精算患者和移植物存活率分别为84.9%和80.1%。有535份肝活检样本可供评估，包括18份切除的同种异体移植物。另外三份功能正常的同种异体移植物的活检标本显示有慢性排斥反应的证据。在这些受者中，由于危及生命的感染、不依从或两者兼而有之，免疫抑制已停止或大幅减少。在恢复基线免疫抑制后，所有三名儿童的肝功能恢复正常，同种异体移植物得以维持；目前存活的肝移植患者肝功能正常。
本研究结果表明，在接受基于他克莫司的免疫抑制的小儿肝移植受者中，只要维持基线免疫抑制，就不会发生慢性排斥反应。
