Oton E, Barcena R, Castillo M, Barreales M, Blesa C, Moreno-Planas J M, Barrios C, Garrido A, Cuervas V
Gastroenterology and Hepatology Service, Hospital Ramón y Cajal, Madrid.
Transplant Proc. 2006 Oct;38(8):2499-501. doi: 10.1016/j.transproceed.2006.08.055.
Cyclosporine has recently been reported to produce in vitro suppression of hepatitis C virus replication driven by blockade of cyclophilins, an effect not shown for tacrolimus. However, the clinical consequence of this in vitro finding have not been well studied in vivo. We compared viral load and fibrosis in transplanted patients receiving monotherapy with tacrolimus or cyclosporine. Patients with recurrent hepatitis C after transplantation were selected from two tertiary centers with the following inclusion criteria: monotherapy with tacrolimus or cyclosporine for more than 12 months before viral load measurement, no antiviral treatment, corticosteroids stopped within 12 months after transplantation. HIV, hepatitis B, and active infection by cytomegalovirus were excluded. Patient characteristics, viral load, and fibrosis were compared by univariate analysis between the cyclosporine and tacrolimus groups. Significant variables, viral load, and fibrosis were included in a multivariate model. Sixty-six patients were included, 46 on tacrolimus and 20 on cyclosporine. Fifty-six were male, and the mean age was 55.3 +/- 10.1 years. Fibrosis (Ishak score) was 3.9 +/- 1.9 in the cyclosporine group and 2.7 +/- 1.9 in the tacrolimus group (P = .019). Viral load (log(10)IU/mL) was 5.8 +/- 0.5 and 5.9 +/- 0.5, respectively (P = .7) and time since liver transplantation was 95.3 +/- 47.7 and 41.1 +/- 16.8 months (P = .0001). In the multivariate model, viral load (P = .65) and fibrosis (P = .24) were not significantly different and only time since transplantation remained significant (P = .0001). In conclusion, viral load was not different in patients with tacrolimus as compared with cyclosporine, and the lower fibrosis observed in the cyclosporine group lacked significance when considered together with time since liver transplantation.
最近有报道称,环孢素可通过阻断亲环蛋白在体外抑制丙型肝炎病毒复制,而他克莫司未显示出这种作用。然而,这一体外研究结果的临床后果在体内尚未得到充分研究。我们比较了接受他克莫司或环孢素单一疗法的移植患者的病毒载量和纤维化情况。从两个三级中心选取移植后复发性丙型肝炎患者,纳入标准如下:在测量病毒载量前,接受他克莫司或环孢素单一疗法超过12个月,未接受抗病毒治疗,移植后12个月内停用皮质类固醇。排除HIV、乙型肝炎和巨细胞病毒活动性感染。通过单因素分析比较环孢素组和他克莫司组的患者特征、病毒载量和纤维化情况。将显著变量、病毒载量和纤维化纳入多变量模型。共纳入66例患者,46例使用他克莫司,20例使用环孢素。56例为男性,平均年龄为55.3±10.1岁。环孢素组的纤维化(Ishak评分)为3.9±1.9,他克莫司组为2.7±1.9(P = 0.019)。病毒载量(log₁₀IU/mL)分别为5.8±0.5和5.9±0.5(P = 0.7),肝移植后的时间分别为95.3±47.7个月和41.1±16.8个月(P = 0.0001)。在多变量模型中,病毒载量(P = 0.65)和纤维化(P = 0.24)无显著差异,仅移植后的时间仍具有显著性(P = 0.0001)。总之,与环孢素相比,使用他克莫司的患者病毒载量无差异,且环孢素组观察到的较低纤维化与肝移植后的时间综合考虑时缺乏显著性。