我们进行了一项随机对照试验来测试移植前采用PEG-INF-α-2b联合利巴韦林(Peg-IFN-α2b/RBV)抗病毒治疗以预防移植后丙肝复发方案的有效性和安全性。受试者为丙肝患者，具有活体供者，肝癌患者MELD评分符合供肝分配标准，他们被列入肝移植名单。基因1/4/6型患者（ n = 44/2/1）以2:1比例被随机分到治疗组(n = 31) 和对照组(n = 16); 基因2/3型患者(n=32)被分到治疗组。最终，59人被治疗，20人未治疗。PEG-INF-α-2b初始剂量为0.75ug/kg，1/周；利巴韦林初始剂量为600mg/d，耐受后再加量。治疗组与对照患者基线特征相似。联合病毒学应答包括移植前SVR和移植后SVR，定义为抗病毒治疗结束和肝移植结束后12w均检测不到HCV RNA。在意向性治疗的分析中，治疗组中12人(19%)和对照组中1人(6%) 实现了CVR(P = 0.29)；每一个治疗方案的值为13 (22%) and 0 (0%) (P = 0.03).治疗组的基因1/4/6型患者中，30例抗病毒治疗患者有23例接受了肝移植，其中22%的患者实现了pTVR；在治疗组的基因2/3型的患者中，29例抗病毒治疗患者有21例接受了肝移植，其中29%的患者实现了pTVR。抗病毒治疗小于8周、8-16周、大于16周的患者pTVR的比率分别为0%, 18%, 50%。在抗病毒治疗病人和未治疗病人中严重不良事件发生率相似（P = 0.30），但每个患者发生不良事件的次数在接受治疗的病人中更高(P = 0.003).入组患者中移植前采用Peg-IFN-α2b/RBV抗病毒治疗预防了移植后丙肝复发，治疗大于16周效果更好，但是潜在发生严重并发症的风险更高。
吉林大学第一医院肝病科 李曼婷 摘译
本文首次发表于[Hepatology,2013,57(5):1752-1762]
A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after livertransplantation.
Abstract
Hepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized, controlled trial to test the efficacy and safety of pretransplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-α2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or Model for End-Stage Liver Disease upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n = 44/2/1) were randomized 2:1 to treatment (n = 31) or untreated control (n = 16); HCV G2/3 (n=32) were assigned to treatment. Overall, 59 were treated and 20 were not. Peg-IFN-α2b, starting at 0.75 μg/kg/week, and RBV, starting at 600 mg/day, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pretransplant sustained virologic response and post-transplant virologic response (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR (P = 0.29); per-protocol values were 13 (22%) and 0 (0%) (P = 0.03). Among treated G1/4/6 patients, 23 of 30 received transplant, of whom 22% had pTVR; among treated G2/3 patients 21 of 29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for <8, 8-16, and >16 weeks, respectively (P = 0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% versus 55%; P = 0.30), but the number of SAEs per patient was higher in the treated group (2.7 versus 1.3; P = 0.003). Conclusion: Pretransplant treatment with Peg-IFN-α2b/RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with >16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.
