肝移植（LT）后发生肾功能不全较常见，>75％的接受LT患者在> 3年随访期出现血清肌酐>1.6 mg /dL。LT后HCV复发几乎是普遍的，〜30％的患者在5年内进展为肝硬化；一些患者因1年内迅速进展为纤维化淤胆性肝炎死亡。使用干扰素和基于利巴韦林方案治疗LT患者，当存在肾功能不全（RI）时存在治疗挑战。LT前应用SOF/ SIM能提高80-90％患者的持续病毒学应答率（SVR），但LT后的公布数据尚缺乏。至少理论上担忧在肾功能不全时使用sofosbuvir，因为主要代谢物GS-331007经肾脏排泄，RI时堆积。
因此，一项研究旨在评估sofosbuvir加simeprevir治疗（SOF+SIM）对LT术后复发性丙型肝炎病毒（HCV）感染患者肾功能的影响，即使存在RI。这是在紧急寻找LT术后安全、有效的治疗方案。研究结果将在AASLD2014上公布。
研究方法
前瞻性研究SOF/ SIM对26例LT后复发性丙型肝炎基因型1患者（男17例，女9例）肾功能的效果，比较治疗开始时（T0）和治疗12周结束（EOT）时的GFR（mL/min）；未校正剂量。GFR变化定义为差别5> mL/min，≤5 mL/min定义为“无变化”。
研究结果
16例患者的GFR无变化，7例改善，3例下降。7例改善患者的GFR改变分别为：42-57; 47-60; 36-50; 7-36（发生治疗期间透析）; 52-59; 37-60; 40-54。下降患者的GFR分别为30-20（DM+ HTN和治疗前进行性肾功能不全）; 15-7（治疗前肾穿刺激发HCV，导致肾功能衰竭）; 60-49（液体摄入减少后降低）。 T0时GFR>60:30-59:<30 mL/min的患者比例为13：11：2，与此相比，EOT时比例为16：8：2。5例患者在LT后一个月开始SOF+ SIM治疗，12例患者在<12月开始治疗，范围0-72个月，平均为LT后18个月。迄今HCV病毒应答取得了巨大成功，方案耐受性良好。
结论
Sofosbuvir加Simepravir对于即使在近期进行移植术的患者和LT后肾功能不全的患者是安全的。肾功能无持续下降，改善的患者（7）多于下降的患者（3），1例出现透析。 3/26例患者GFR下降，在开始治疗前或可由与SOF/ SIM治疗无关的因素解释。
英文原文
Renal function in liver transplant patients treated for recurrent hepatitis C with sofosbuvir and simeprevir.（摘要号：LB-24）
Purpose: To assess the effect of sofosbuvir plus simeprevir treatment (sof/sim) on renal function in post liver transplant (LT) patients treated for recurrent hepatitis C (HCV), even in the presence of renal insufficiency (RI).
Background: Renal insufficiency is common after LT, serum creatinine >1.6 mg/dL is found in >75% of LT recipients after >3 years of follow up. HCV recurrence post-LT is nearly universal and ~30% of patients progress to cirrhosis within 5 years; some succumb to a rapidly progressing fibrosing cholestatic hepatitis within a year. Hence there is some urgency in finding safe and effective regimens for use post-LT even with RI. Treatment of LT patients with interferon and ribavirin-based therapies is challenging with RI. Sustained virological response (SVR) rates have improved to 80-90% with sof/sim pre-LT, but there is little published data post-LT. There are at least theoretical concerns in using sofosbuvir in renal insufficiency since the main metabolite GS-331007 is renally excreted and accumulates in RI.
Methods: Prospective study of the effect of sof/sim on renal function in 26 post-LT patients (17 male, 9 female) with recurrent hepatitis C genotype 1 by comparison of GFR (mL/min) at the start of treatment (T0) and end of treatment (EOT) week 12; no dose adjustments were made. A change in GFR was defined as a difference of >5 mL/min, less as “unchanged”.
Results: GFR was unchanged in 16 patients, improved in 7 and declined in 3. The GFR of those 7 who improved went from: 42 to 57; 47-60; 36-50; 7-36 (came off dialysis during treatment); 52-59; 37-60; 40-54. The GFR of those who declined went from 30 to 20 (DM+HTN and progressive renal insufficiency PRE-treatment); 15-7 (renal biopsy pre-treatment invoked HCV as contributing to renal failure); 60-49 (declined after reduced fluid intake). The distribution of patients having a GFR of >60:30-59:<30 mL/min was 13:11:2 at T0 compared to 16:8:2 at EOT. Treatment with sof+sim was started <1 month post-LT in 5 patients and <12 months in 12 patients, range 0-72, median 18 months post-LT. HCV viral response to date has been highly successful and the regimen well tolerated.
Conclusion: Sofosbuvir plus Simepravir seems to be safe even in recently transplanted patients and in those post-LT patients with renal insufficiency. There was no consistent decline in renal function, more patients (7) improved than declined (3), one came off dialysis. 3/26 patients had a decline in GFR either starting before treatment or explicable by factors unrelated to the sof/sim treatment.
