Tisone Giuseppe, Orlando Giuseppe, Cardillo Andrea, Palmieri Giampiero, Manzia Tommaso Maria, Baiocchi Leonardo, Lionetti Raffaella, Anselmo Alessandro, Toti Luca, Angelico Mario
Liver Transplant Unit, Surgical Clinic, University of Rome Tor Vergata, S. Eugenio Hospital, Viale dell'Umanesimo 10, 00144, Rome, Italy.
J Hepatol. 2006 Apr;44(4):702-9. doi: 10.1016/j.jhep.2005.11.047. Epub 2006 Jan 4.
BACKGROUND/AIMS: HCV-related disease recurrence progresses rapidly after liver transplantation. We hypothesised that withdrawal of immunosuppression might favourably impact on disease progression.
Weaning off immunosuppression was attempted in 34 HCV-RNA positive patients (mean age 62+/-6.4 years) transplanted 63.5+/-20.1 months earlier, under cyclosporine A monotherapy. Patients were followed for 3 years including yearly protocol liver biopsies. Primary endpoints were feasibility of weaning off immunosuppression and its impact on disease progression. Secondary endpoint was to identify predictors of an immunosuppression-free state and fibrosis progression.
Complete and permanent immunosuppression withdrawal was achieved in 8 patients (23.4%), whereas 14 (41.2%) developed rejection within eight months despite an initial response and 12 (35.2%) rejected during tapering. After a mean follow-up 45.5+/-5.8 months weaned patients showed stabilisation/improvement of histological fibrosis (P<0.01), lower necro-inflammation (P<0.02) and improved liver function (P<0.05) compared to weaning-intolerants. Multiple logistic regression identified low blood cyclosporine A trough levels during the first post-transplant week (P=0.004) and initial steroid-free immunosuppression (P<0.008) as independent predictors of sustained weaning. Achievement of immunosoppression freedom (P=0.02) and baseline staging score (P<0.0001) were independently associated with stabilisation/improvement of histological fibrosis.
Reconstitution of immune-competence in the host improves the natural history of HCV recurrence in the graft.
背景/目的：肝移植后丙型肝炎病毒（HCV）相关疾病复发进展迅速。我们推测停用免疫抑制可能对疾病进展产生有利影响。
对34例HCV-RNA阳性患者（平均年龄62±6.4岁）尝试停用免疫抑制，这些患者在63.5±20.1个月前接受移植，采用环孢素A单一疗法。对患者进行3年随访，包括每年的常规肝脏活检。主要终点是停用免疫抑制的可行性及其对疾病进展的影响。次要终点是确定无免疫抑制状态和纤维化进展的预测因素。
8例患者（23.4%）实现了完全且永久性的免疫抑制停用，而14例（41.2%）尽管最初有反应但在8个月内发生了排斥反应，12例（35.2%）在减量过程中发生了排斥反应。在平均随访45.5±5.8个月后，与不耐受停用的患者相比，成功停用免疫抑制的患者组织学纤维化稳定/改善（P<0.01），坏死性炎症减轻（P<0.02），肝功能改善（P<0.05）。多因素逻辑回归分析确定移植后第一周血中环孢素A谷浓度低（P=0.004）和初始无类固醇免疫抑制（P<0.008）是持续停用免疫抑制的独立预测因素。实现无免疫抑制状态（P=0.02）和基线分期评分（P<0.0001）与组织学纤维化的稳定/改善独立相关。
宿主免疫能力的重建改善了移植物中HCV复发的自然病程。
