Department of digestive surgery and liver transplantation, Aix-Marseille University, hôpital La Conception, Assistance publique-hôpitaux de Marseille, 13005 Marseille, France.
J Hepatol. 2013 Dec;59(6):1223-30. doi: 10.1016/j.jhep.2013.07.032. Epub 2013 Aug 6.
BACKGROUND & AIMS: Calcineurin inhibitors represent the cornerstone immunosuppressants after liver transplantation despite their side effects. As liver graft is particularly well tolerated, low doses may be proposed. The aim of this study was to assess the prevalence of chronic rejection in patients with low calcineurin inhibitors regimen and to compare their characteristics with patients under standard doses.
All patients with liver transplantation between 1997 and 2004 were divided into two groups. Low-dose patients (n=57) had tacrolimus baseline levels <5ng/ml or cyclosporine levels <50ng/ml at t0 or <100ng/ml at t+2h and were prospectively proposed a liver biopsy, searching for chronic rejection according to Banff criteria. The remaining patients constituted the standard-doses group (n=40).
Among the low-dose group, 36 patients in the low-dose group were assessed by biopsy. No chronic rejection was found. Fifty-six percent had only calcineurin inhibitors and 8% received other immunosuppressants only. The median time between liver transplantation and biopsy was 90 months (64-157) and between IS regimen decrease and biopsy was 41 months (11-115). Liver tests were normal in 72% of the patients. Low-dose patients had more often hepatitis B (p=0.045), less past acute rejection episodes (p=0.028), and better renal function (p=0.040). Decrease of calcineurin inhibitors failed in 15% of standard-dose patients without impacting the graft function. In the low-dose group, co-prescription of other immunosuppressants facilitated the decrease (p=0.051).
The minimization, or even cessation, of calcineurin inhibitors may be an achievable goal in the long term for most of the liver graft recipients.
钙调磷酸酶抑制剂是肝移植后免疫抑制的基石，但存在副作用。由于肝移植物具有良好的耐受性，因此可以使用低剂量。本研究旨在评估低钙调磷酸酶抑制剂方案患者慢性排斥反应的发生率，并比较其与标准剂量患者的特征。
1997 年至 2004 年间所有接受肝移植的患者分为两组。低剂量组（n=57）在 t0 时他克莫司基线水平<5ng/ml 或环孢素水平<50ng/ml 或 t+2h 时<100ng/ml，前瞻性地建议进行肝活检，根据 Banff 标准寻找慢性排斥反应。其余患者构成标准剂量组（n=40）。
低剂量组中，36 例患者接受了活检。未发现慢性排斥反应。56%的患者仅使用钙调磷酸酶抑制剂，8%的患者仅使用其他免疫抑制剂。肝移植与活检之间的中位时间为 90 个月（64-157），免疫抑制方案减少与活检之间的中位时间为 41 个月（11-115）。72%的患者肝功能正常。低剂量组乙型肝炎发生率较高（p=0.045），过去急性排斥反应发作较少（p=0.028），肾功能较好（p=0.040）。标准剂量组中有 15%的患者减少钙调磷酸酶抑制剂治疗失败，但未影响移植物功能。在低剂量组中，同时使用其他免疫抑制剂有助于减少剂量（p=0.051）。
对于大多数肝移植受者，钙调磷酸酶抑制剂的最小化甚至停止使用可能是一个长期可行的目标。
