Hepatitis C virus therapy, hepatocyte drug metabolism, and risk for acute cellular rejection
Hepatitis C virus therapy, hepatocyte drug metabolism, and risk for acute cellular rejection
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DOI：
10.1053/jlts.2003.50233
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发表时间：
2003-11-01
影响因子：
4.6
通讯作者：
Everson, GT
中科院分区：
文献类型：
--
作者：
Kugelmas, M;Osgood, MJ;Everson, GT
我们最近报道了一系列在移植后队列中治疗丙型肝炎病毒（HCV）感染期间发生急性细胞排斥反应（ACR）的患者。我们的假设是，HCV清除改善肝微粒体功能，这反过来又导致较低的谷环孢素（CyA）和他克莫司（TAC）水平，使患者易患ACR。我们回顾了1993年至2002年6月在我们中心接受HCV感染移植的所有患者的记录。确定了203名患者。37例患者（18%）接受干扰素联合利巴韦林治疗。选择12例患者进行分析，因为他们在治疗过程中成为HCV RNA阴性，18例无抗病毒应答的患者被选为对照（7例其他患者数据不完整或从一种免疫抑制[IS]治疗转换为另一种）。将基线IS水平与研究组中记录的HCV RNA阴性结果后的第一个可用水平和对照组中的最后一个治疗IS水平进行比较。我们还比较了治疗期间IS水平变化的频率和百分比。研究组的CyA谷浓度平均从基线时的187.28 ng/mL下降至HCV RNA阴性后即刻的118.14 ng/mL（-36.92%; P = 0.018）。TAC水平从基线时的7.34 ng/mL平均下降至HCV RNA阴性后即刻的5.02 ng/mL（-29.17%; P = .044）。总体而言，治疗期间清除HCV RNA的12例患者中有6例发生ACR; 1例患者因ACR死亡。使用从基线IS水平降低的百分比，我们合并了给予CyA和TAC的患者的结果，发现应答者的IS水平从基线显著降低（治疗期间HCV RNA清除后-31.8%; P = .0001）。无应答者在治疗期间IS水平下降0.98%，与应答者组的变化相比差异显著（P = .006）。在治疗期间，抗病毒治疗应答者中IS谷水平较基线降低20%的比例也高于无应答者对照组（P = .0006）。总之，IS水平显着下降，积极响应抗HCV治疗的患者。IS水平的降低可能在这些患者发生ACR的易感性中起关键作用。
We recently reported on a series of patients who experienced acute cellular rejection (ACR) during the treatment of hepatitis C virus (HCV) infection in our posttransplantation cohort. Our hypothesis is that HCV clearance improves hepatic microsomal function, which in turn results in lower trough cyclosporine (CyA) and tacrolimus (TAC) levels, predisposing the patient to ACR. Records of all patients receiving transplants for HCV infection at our center from 1993 to June 2002 were reviewed. Two hundred three patients were identified. Thirty-seven patients (18%) were treated with interferon-hased therapies in combination with ribavirin. Twelve patients were selected for analysis because they became HCV RNA negative during therapy, and 18 patients with no antiviral response were selected as controls (7 other patients had incomplete data or had switched from one immunosuppression [IS) therapy to the other). Baseline IS levels were compared with the first available level after documented negative HCV RNA results in the study group and the last on-treatment IS level in the control group. We also compared frequency and percentage of change in IS levels during therapy. Mean decline in CyA trough levels in the study group was from 187.28 ng/mL at baseline to 118.14 ng/mL immediately after becoming HCV RNA negative (-36.92%; P = .018). Mean decline in TAC levels was from 7.34 ng/mL at baseline to 5.02 ng/mL immediately after becoming HCV RNA negative (-29.17%; P = .044). Overall, 6 of 12 patients who cleared HCV RNA during therapy experienced ACR; 1 patient died as a result of ACR. Using percentage of decrease from baseline IS level, we combined results for patients administered CyA and TAC and found a significant decrease from baseline IS levels in responders (-31.8% after HCV RNA clearance on treatment; P = .0001). Nonresponders experienced a 0.98% decline in IS levels while on treatment, and the difference was significant compared with the change in the responder group (P = .006). A greater proportion of antiviral therapy responders also experienced trough IS levels 20% less than baseline than nonresponder controls during therapy (P = .0006). In conclusion, IS levels decreased significantly in patients responding favorably to anti-HCV therapy. This decrease in IS levels may have a key role in predisposing these patients to ACR.