Alberti A B, Belli L S, Airoldi A, de Carlis L, Rondinara G, Minola E, Vangeli M, Cernuschi A, D'Amico M, Forti D, Pinzello G
Department of Medicine Crespi, Center for Liver Diseases, Milan, Italy.
Liver Transpl. 2001 Oct;7(10):870-6. doi: 10.1053/jlts.2001.27871.
Recurrent hepatitis C is a common problem after liver transplantation that can progress to liver cirrhosis of the graft. Preliminary reports of combination treatment with interferon (IFN) and ribavirin have been promising, but long-term follow-up data are not yet available. We report our experience with 1 year of combination therapy with IFN (3 million units thrice weekly) and low-dose ribavirin (600 mg/d), followed by long-term ribavirin monotherapy in 18 patients with moderate to severe recurrent hepatitis C and a median follow-up of 32 months after the completion of combined therapy. All patients were followed up clinically and histologically at regular intervals. Overall, in an intention-to-treat analysis, 15 patients had normal alanine aminotransferase levels (biochemical end-treatment response [ETR], 83%), and 8 patients were also hepatitis C virus RNA negative in serum (virological ETR, 44%) at the end of combined treatment. At last follow-up after the completion of combined therapy (median, 32 months; range, 18 to 73 months), 13 patients were biochemical responders (biochemical long term-sustained response [LT-SR], 72%), and 5 patients also maintained viral clearance (virological LT-SR, 27%). Comparison of liver biopsy specimens before and after 12 months of combined therapy showed improvement in grading scores of at least two points in the majority of the patients (73%). Notably, a trend toward fibrotic progression was only noted in nonresponders. Regarding side effects, despite the low dose of ribavirn, almost half the patients developed hemolytic anemia requiring dose reductions. In addition, long-term ribavirin monotherapy was not associated with iron accumulation. We conclude that combined therapy with low-dose ribavirin followed by long-term ribavirin monotherapy can be recommended because it favorably modifies the natural history of recurrent hepatitis C in most patients and possibly halts histological disease progression without causing iron accumulation.
复发性丙型肝炎是肝移植后常见的问题，可进展为移植肝肝硬化。干扰素（IFN）与利巴韦林联合治疗的初步报告显示前景良好，但长期随访数据尚未可得。我们报告了18例中重度复发性丙型肝炎患者接受IFN（300万单位，每周3次）与低剂量利巴韦林（600mg/d）联合治疗1年，随后长期接受利巴韦林单药治疗的经验，联合治疗结束后中位随访32个月。所有患者均定期接受临床和组织学随访。总体而言，在意向性治疗分析中，联合治疗结束时15例患者丙氨酸氨基转移酶水平正常（生化治疗结束反应[ETR]，83%），8例患者血清丙型肝炎病毒RNA也呈阴性（病毒学ETR，44%）。联合治疗结束后的最后随访（中位时间32个月；范围18至73个月）时，13例患者为生化反应者（生化长期持续反应[LT-SR]，72%），5例患者也维持病毒清除（病毒学LT-SR，27%）。联合治疗12个月前后肝活检标本比较显示，大多数患者（73%）分级评分至少提高2分。值得注意的是，仅在无反应者中观察到纤维化进展趋势。关于副作用，尽管利巴韦林剂量较低，但几乎一半的患者出现溶血性贫血需要减少剂量。此外，长期利巴韦林单药治疗与铁蓄积无关。我们得出结论，低剂量利巴韦林联合治疗后长期利巴韦林单药治疗值得推荐，因为它能在大多数患者中有利地改变复发性丙型肝炎的自然病程，并可能阻止组织学疾病进展而不引起铁蓄积。
