探究索非布韦联合雷迪帕韦抗病毒治疗方案在肾移植HCV感染受者中的临床疗效。

回顾性分析2011年7月1日至2016年5月1日西安交通大学第一附属医院肾移植术后接受索非布韦联合雷迪帕韦治疗的11例HCV感染受者临床资料。主要观察指标包括快速病毒学应答、早期病毒学应答和持续病毒学应答(SVR)。治疗有效性和安全性评价指标包括血清HCV RNA、AST、ALT、估算肾小球虑过率(eGFR)、血清肌酐及免疫抑制剂血药浓度。同时记录抗病毒药物所引起的不良反应发生情况，如恶心、头晕和失眠等。采用重复测量资料的方差分析或混合线性模型进行比较。P<0.05为差异有统计学意义。

11例受者均顺利完成抗病毒治疗，随访至抗病毒治疗结束后12周，均获得SVR，在治疗结束时均未检测到HCV RNA。11例受者治疗前HCV RNA载量为2.1×10⁶ IU/mL(5.6×10³，7.3×10⁶)IU/mL，治疗第8周及治疗结束时HCV RNA载量为4.5×10² IU/mL(3.2×10²，5.7×10²)IU/mL和1.2×10² IU/mL(0.8×10²，2.5×10²)IU/mL，差异有统计学意义(F＝0.515，P<0.05)。11例受者抗HCV治疗前ALT、AST和谷氨酰转肽酶水平分别为(58±31)U/L(18~211 U/L)、(47±29)U/L(21~109 U/L)和(147±68)U/L(32~404 U/L)，治疗结束时分别为(17±8)U/L(10~38 U/L)、(19±7)U/L(12~36 U/L)和(32±22)U/L(17~106 U/L)，差异均有统计学意义(t＝4.350、2.159和7.251，P均<0.05)；抗HCV治疗前eGFR为(71±23)mL·min^－1·(1.73 m²)^－1[38~106 mL·min^－1·(1.73 m²)^－1]，治疗结束时为(70±25)mL·min^－1·(1.73 m²)^－1[41~110 mL·min^－1·(1.73 m²)^－1]，差异无统计学意义(t＝0.760，P>0.05)；抗HCV治疗前、治疗第4周、治疗结束时他克莫司血药浓度谷值分别为(7.3±2.8)、(7.2±2.6)和(6.9±1.9)ng/mL，差异无统计学意义(F＝0.423，P>0.05)。随访期间4例受者出现不良反应，其中失眠、头晕、腹泻和下肢疼痛各1例。

索非布韦联合雷迪帕韦治疗方案对慢性HCV感染肾移植受者具有良好的耐受性、安全性和有效性。

To investigate the clinical efficacy of sofosbuvir combined with ledipasvir antiviral therapy in renal transplant recipients with HCV infection.

The clinical data of 11 HCV-infected recipients treated with sofosbuvir combined with raltegravir after renal transplantation at the First Affiliated Hospital of Xi′an Jiaotong University from July 1, 2011 to May 1, 2016 were retrospectively analyzed. The main observation indexes included rapid virological response, early virological response and sustained virological response (SVR). Indicators of treatment efficacy and safety included serum HCV RNA, AST, ALT, estimate glomerular filtration rate (eGFR), serum creatinine and immunosuppressive drug blood trough levels. The incidence of adverse effects caused by antiviral drugs such as nausea, dizziness and insomnia was also recorded. The repeated measurement data analysis of variance or the mixed linear model were used for comparison. P<0.05 was considered statistically significant.

All 11 recipients completed antiviral treatment and were followed up to 12 weeks after the end of antiviral treatment. All recipients achieved SVR and none had detectable HCV RNA at the end of treatment. HCV RNA loads were 2.1×10⁶ IU/mL (5.6×10³, 7.3×10⁶) before treatment and 4.5×10² IU/mL (3.2×10², 5.7×10²) IU/mL and 1.2×10² IU/mL (0.8×10², 2.5×10²) IU/mL at week 8 and at the end of treatment in 11 recipients, with statistically significant difference (F=0.515, P<0.05). ALT, AST and glutamyl transpeptidase levels were (58±31) U/L (18-211 U/L) , (47±29) U/L (21-109 U/L) and (147±68) U/L (32-404 U/L) respectively before anti-HCV treatment, and (17±8) U/L (10-38 U/L) , (19±7) U/L (12-36 U/L) and (32±22) U/L (17-106 U/L) respectively at the end of antiviral treatment in 11 recipients, all with statistically significant differences (t=4.350, 2.159 and 7.251, P<0.05). The eGFR was (71±23) mL·^-1·(1.73 m²)^-1[38-106 mL·min^-1·(1.73 m²) ^-1] before anti-HCV treatment, and (70±25) mL·min^-1·(1.73 m²) ^-1 [41-110 mL·min^-1·(1.73 m²)^-1] at the end of treatment; the difference was not statistically significant (t=0.760, P>0.05). The trough values of tacrolimus blood concentrations before anti-HCV treatment, at week 4 of treatment and at the end of treatment were (7.3±2.8) , (7.2±2.6) and (6.9±1.9)ng/mL respectively, with no statistically significant difference (F=0.423, P>0.05). During the follow-up period, four recipients experienced adverse effects, including insomnia, dizziness, diarrhoea and lower limb pain in one case each.

Sofosbuvir combined with ledipasvir treatment regimen is well tolerated, safe and effective in renal transplant recipients with chronic HCV infection.