Sharma R K, Bansal S B, Gupta A, Gulati S, Kumar A, Prasad N
Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Clin Transplant. 2006 Nov-Dec;20(6):677-83. doi: 10.1111/j.1399-0012.2006.00534.x.
Chronic hepatitis C virus (HCV) infection is a common cause of liver disease in post-renal transplant period and causes poor patient and graft survival. We analyzed the effects of antiviral therapy using ribavirin monotherapy or ribavirin in combination with interferon (IFN)-alpha in our kidney transplant recipients with chronic hepatitis C.
Total of 14 patients received antiviral therapy, all of whom had stable graft function, raised aminotransferases and positive HCV viremia at the start of treatment. Eight patients received ribavirin alone for a period of six months to two yr, in doses of 400-800 mg daily. Five patients received IFN-alpha therapy for a period of two months to 1.5 yr, in doses of 1.5 million units daily or three million units thrice weekly with ribavirin. One patient received pegylated IFN 50 microg once weekly in combination with ribavirin. The response was seen in terms of biochemical and virological improvement at the end of study period.
In patients treated with ribavirin alone (n = 8), mean alanine aminotransferase (ALT) levels before and after treatment were significantly different (198.4 +/- 147.6 and 104.8 +/- 66.5 IU/L respectively; p < 0.05). ALT levels normalized completely in three patients at the end of treatment, improved in three patients and deteriorated in two. Only in one of eight patients on ribavirin alone, HCV-RNA became negative after six months of treatment while in the rest (n = 7) HCV-RNA continued to be positive. In subjects on IFN plus ribavirin (n = 6), the mean ALT levels decreased significantly (from 280.2 +/- 114.9 IU/L at baseline to 71 +/- 49 IU/L at end of therapy; p < 0.05). Two patients had sustained remission (33.3%) on IFN plus ribavirin (persistently negative HCV-RNA), two patients relapsed after initial remission and in two patients treatment was stopped after two months because of graft dysfunction. Totally four patients developed graft dysfunction at some time during the course of IFN therapy (66.6%), but it was discontinued in only two (33.3%). All patients regained normal creatinine levels after discontinuation of IFN, although one patient developed chronic allograft nephropathy as shown by kidney biopsy. Four patients in IFN group developed leucopenia. Two patients developed severe anemia one of whom required blood transfusion and one developed severe flu-like syndrome requiring stoppage of therapy.
Ribavirin monotherapy in renal transplant recipients with chronic hepatitis C infection results in good biochemical response but is not associated with virological clearance. IFN in combination with ribavirin is effective in two-thirds of patients after a minimum therapy of six months, but it is poorly tolerated, results in graft dysfunction in significant number of patients, and relapse can occur after stopping treatment.
慢性丙型肝炎病毒（HCV）感染是肾移植术后肝病的常见病因，会导致患者及移植物存活率降低。我们分析了利巴韦林单药治疗或利巴韦林联合α干扰素（IFN）抗病毒治疗对我们肾移植术后慢性丙型肝炎患者的影响。
共有14例患者接受抗病毒治疗，所有患者在治疗开始时移植肾功能稳定、转氨酶升高且HCV病毒血症呈阳性。8例患者单独接受利巴韦林治疗6个月至2年，每日剂量为400 - 800 mg。5例患者接受IFN-α治疗2个月至1.5年，每日剂量为150万单位，或每周三次，每次300万单位，同时服用利巴韦林。1例患者接受聚乙二醇化IFN 50 μg每周一次联合利巴韦林治疗。在研究期末根据生化和病毒学改善情况评估疗效。
单独接受利巴韦林治疗的患者（n = 8），治疗前后平均丙氨酸转氨酶（ALT）水平有显著差异（分别为198.4±147.6和104.8±66.5 IU/L；p < 0.05）。治疗结束时3例患者ALT水平完全恢复正常，3例有所改善，2例恶化。单独接受利巴韦林治疗的8例患者中，仅1例在治疗6个月后HCV - RNA转为阴性，其余7例HCV - RNA仍为阳性。接受IFN联合利巴韦林治疗的患者（n = 6），平均ALT水平显著下降（从基线时的280.2±114.9 IU/L降至治疗结束时的71±49 IU/L；p < 0.05）。2例患者在接受IFN联合利巴韦林治疗后持续缓解（33.3%）（HCV - RNA持续阴性），2例患者在初始缓解后复发，2例患者因移植肾功能障碍在治疗2个月后停药。在IFN治疗过程中，共有4例患者在某个时间出现移植肾功能障碍（66.6%），但仅2例（33.3%）停药。停用IFN后所有患者肌酐水平恢复正常，尽管1例患者经肾活检显示发生了慢性移植肾肾病。IFN组4例患者出现白细胞减少。2例患者出现严重贫血，其中1例需要输血，1例出现严重流感样综合征需要停药。
利巴韦林单药治疗肾移植术后慢性丙型肝炎感染患者可产生良好的生化反应，但与病毒学清除无关。IFN联合利巴韦林治疗至少6个月后，三分之二的患者有效，但耐受性差，导致相当数量的患者出现移植肾功能障碍，且停药后可能复发。
