Faisal Nabiha, Bilodeau Marc, Aljudaibi Bandar, Hirsch Geri, Yoshida Eric M, Hussaini Trana, Ghali Maged P, Congly Stephen E, Ma Mang M, Leonard Jennifer, Cooper Curtis, Peltekian Kevork, Renner Eberhard L, Lilly Leslie B
1 Multiorgan Transplant, University Health Network/Toronto General Hospital, University of Toronto, Toronto, ON, Canada. 2 Liver Unit, Department of Medicine, Université de Montréal, Montréal, Québec, Canada. 3 Department of Gastroenterology, London Health Sciences, University of Western Ontario, London, ON, Canada. 4 King Saud University, Riyadh, Saudi Arabia. 5 Department of Hepatology, Dalhousie University/Queen Elizabeth II health Science Center, Halifax, NS, Canada. 6 Department of Gastroenterology, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada. 7 Solid organ Transplantation, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada. 8 Department of Gastroenterology and Hepatology, University of McGill, Montreal, Québec, Canada. 9 Department of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada. 10 Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada. 11 Department of Gastroenterology, Memorial University, St. John's, NL, Canada. 12 Division of Infectious diseases, University of Ottawa, Ottawa, ON, Canada. 13 Division of Gastroenterology, Dalhousie University/Queen Elizabeth II Health Science Center, Halifax, NS, Canada.
Transplantation. 2016 May;100(5):1059-65. doi: 10.1097/TP.0000000000001126.
This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers.
One hundred twenty liver transplantation recipients from across Canada with HCV recurrence were started on SOF-based regimens (SOF + simeprevir ± ribavirin (RBV), n = 53; SOF + pegylated interferon + RBV, n = 25; SOF + RBV, n = 36; and SOF + ledipasvir, n = 6) between January and November 2014. Mean age 58 ± 6.85 years, majority (83%) were genotype 1, male (81%), and treatment experienced (82%). Twenty-seven percent had fibrosing cholestatic hepatitis/early aggressive HCV in the graft, and 48% had F3/4 fibrosis. The primary outcomes included patient and graft survival, on- and end-of-treatment response and sustained virological response at 12 weeks after treatment end (SVR12), and adverse events.
One hundred thirteen of 120 (94%) patients were HCV RNA undetectable at end of treatment, and SVR12 was achieved in 102/120 (85%) patients, with 7 relapses, 1 nonresponder, and 10 deaths (liver-related complications). Sixty-three percent had HCV RNA levels below the lower limit of quantification at week 4. Serum creatinine levels remained stable throughout the treatment. Severe anemia occurred in 13% of patients, primarily in RBV-based regimens.
Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.
本研究评估了含索磷布韦（SOF）方案在加拿大所有移植中心的非临床试验患者中治疗所有基因型丙型肝炎病毒（HCV）复发的疗效、安全性和耐受性。
2014年1月至11月期间，来自加拿大各地的120例HCV复发的肝移植受者开始接受基于SOF的方案治疗（SOF + 西米普明 ± 利巴韦林（RBV），n = 53；SOF + 聚乙二醇干扰素 + RBV，n = 25；SOF + RBV，n = 36；以及SOF + 来迪派韦，n = 6）。平均年龄58 ± 6.85岁，大多数（83%）为1型基因型，男性（81%），且有治疗史（82%）。27%的患者移植肝出现纤维性胆汁淤积性肝炎/早期侵袭性HCV，48%的患者有F3/4级纤维化。主要结局包括患者和移植物存活情况、治疗期间和治疗结束时的反应以及治疗结束后12周的持续病毒学应答（SVR12）和不良事件。
120例患者中有113例（94%）在治疗结束时HCV RNA检测不到，102/120例（85%）患者实现了SVR12，有7例复发，1例无反应者，10例死亡（肝脏相关并发症）。63%的患者在第4周时HCV RNA水平低于定量下限。整个治疗过程中血清肌酐水平保持稳定。13%的患者出现严重贫血，主要发生在基于RBV的方案中。
肝移植后HCV复发的基于索磷布韦的抗病毒治疗耐受性良好，总体SVR12率较高（85%），包括疾病复发严重和F3 - 4级肝硬化的患者。轻度HCV复发患者的应答率更高（91%），提示早期治疗可能有益。
