Guitard J, Sandres-Sauné K, Kamar N, Ribes D, Faguer S, Esposito L, Lavit M, Muscari F, Péron J M, Lavayssière L, Durand D, Rostaing L
Department of Nephrology, Dialysis, and Multiorgan Transplant Unit, CHU Rangueil, 1 avenue Jean Poulhès, 31059 Toulouse, France.
Transplant Proc. 2007 Oct;39(8):2603-5. doi: 10.1016/j.transproceed.2007.08.086.
We assessed whether conversion from tacrolimus (TAC) to cyclosporine (CsA) was associated with a reduction in hepatitis C virus (HCV) viral load among HCV-positive liver transplant (OLT) patients.
Nine OLT patients with recurrent HCV have TAC and prednisone immunosuppression. None received any HCV antiviral therapy. After the last intake of TAC, the patients underwent a 12-hour area under the curve (AUC(12)) measurement of both TAC and HCV viral loads. The next morning (D(0)) patients were given CsA (4 mg/kg bid). At the first intake of CsA and at 1 month (M(1)) later, the patients underwent AUC(12) for CsA and HCV viral loads. Biological data, including aspartate (AST) and alanine (ALT) aminotransferase, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), and bilirubin levels, were collected during AUC(12), and at M(1) and M(3).
With respect to liver enzymes (AST, ALT, GGT), there was no significant difference between D(0), M(1), and M(3). Conversely, there was a significant decrease in AP between D(0) and M(3) (P = .02), and a significant increase in total bilirubin between D(0) and M(1) (P = .04), and between D(0) and M(3) (P = .01). HCV viral load significantly increased by M(3) (P = .01). At no time (D(0), M(1)) was there any correlation between the AUC(12) of TAC or CsA, and between AUC(12) HCV viral load.
This pilot study found no acute or chronic anti-HCV effects from CsA that were evident within 12 hours after CsA administrations or beyond 1 month of CsA therapy, respectively.
我们评估了在丙型肝炎病毒（HCV）阳性肝移植（OLT）患者中，从他克莫司（TAC）转换为环孢素（CsA）是否与HCV病毒载量降低有关。
9例复发性HCV的OLT患者接受TAC和泼尼松免疫抑制治疗。均未接受任何HCV抗病毒治疗。在最后一次服用TAC后，患者接受了TAC和HCV病毒载量的12小时曲线下面积（AUC(12)）测量。次日早晨（第0天），患者给予CsA（4mg/kg，每日两次）。在首次服用CsA时以及1个月（第1个月）后，患者接受CsA和HCV病毒载量的AUC(12)测量。在AUC(12)测量期间以及第1个月和第3个月收集生物学数据，包括天冬氨酸（AST）和丙氨酸（ALT）转氨酶、γ-谷氨酰转肽酶（GGT）、碱性磷酸酶（AP）和胆红素水平。
就肝酶（AST、ALT、GGT）而言，第0天、第1个月和第3个月之间无显著差异。相反，AP在第0天和第3个月之间显著降低（P = 0.02），总胆红素在第0天和第1个月之间（P = 0.04）以及第0天和第3个月之间（P = 0.01）显著升高。到第3个月时HCV病毒载量显著增加（P = 0.01）。在任何时间（第0天、第1个月），TAC或CsA的AUC(12)与HCV病毒载量的AUC(12)之间均无相关性。
这项初步研究发现，CsA在给药后12小时内或CsA治疗1个月后均未分别显示出明显的急性或慢性抗HCV作用。
