索磷布韦/维帕他韦联合或不联合利巴韦林治疗慢性丙型肝炎伴慢性肾脏病患者的疗效和安全性分析

Effectiveness and safety of sofosbuvir/velpatasvir with or without ribavirin for patients with chronic hepatitis C and chronic kidney disease

目的评估索磷布韦/维帕他韦(SOF/VEL)联合或不联合利巴韦林治疗慢性丙型肝炎(CHC)伴慢性肾脏病(CKD)患者的疗效和安全性。方法纳入2018年6月至2022年5月在昆明市第三人民医院诊断为CHC伴CKD并接受SOF/VEL±利巴韦林治疗的患者75例,收集患者基本资料,观察患者在基线、治疗4周、治疗12周和停药12周的肾功能、肝功能、病毒学应答率及治疗期间的不良反应。统计学分析采用Wilcoxon秩和检验和Kruskal-Wallis秩和检验。结果75例患者中,CKD 2期51例(68.0%),CKD 3期12例(16.0%),CKD 4期4例(5.3%),CKD 5期8例(10.7%);HCV基因3a型26例(34.7%),基因3b型37例(49.3%);肝硬化患者51例(68.0%),其中肝硬化代偿期15例(20.0%),肝硬化失代偿期36例(48.0%)。停药12周时,患者估计肾小球滤过率(eGFR)[81.76(60.94,94.34)mL/(min·1.73 m^(2))]较基线[70.99(52.86,82.38)mL/(min·1.73 m^(2))]升高,差异有统计学意义(Z=8.12,P=0.040)。基线至停药12周时,CKD 2、3期患者的eGFR值均逐渐升高,差异均有统计学意义(H=8.91、8.03,均P<0.05),其中CKD 2期患者从78.82(70.98,84.80)mL/(min·1.73 m^(2))升至86.94(75.91,96.01)mL/(min·1.73 m^(2));CKD 3期患者从51.24(45.92,53.37)mL/(min·1.73 m^(2))升至64.58(44.54,74.34)mL/(min·1.73 m^(2))。21例(28.0%)患者的肾功能恢复至CKD 1期。相较于基线,停药12周时CKD 2期患者天冬氨酸转氨酶和血小板计数比率指数下降,丙氨酸转氨酶和天冬氨酸转氨酶也明显好转,差异均有统计学意义(Z=8.03、21.57、43.74,均P<0.05)。75例患者在治疗结束后12周持续病毒学应答(SVR12)率为98.7%(74/75)。其中CKD 2期、CKD 3期、CKD 4至5期分别有51例、11例、12例患者达到SVR12。32例(42.7%)患者发生不良事件,其中18例轻度溶血性贫血,4例皮肤瘙痒,3例皮疹,2例胸闷,5例乏力。结论SOF/VEL联合或不联合利巴韦林治疗CHC伴CKD患者具有良好的疗效和安全性,抗病毒治疗后肾功能、肝功能和肝纤维化程度均得到一定改善。

Objective To evaluate the effectiveness and safety of sofosbuvir/velpatasvir(SOF/VEL)with or without ribavirin in the treatment of patients diagnosed with chronic hepatitis C(CHC)and chronic kidney disease(CKD).Methods From June 2018 to May 2022,a total of 75 patients with CHC and CKD,and treated with SOF/VEL±ribavirin at the Kunming Third People′s Hospital were enrolled in this study.The basic information of patients were collected.Assessments of renal function,liver function,virologic response rate and adverse events were conducted at baseline,four weeks and 12 weeks of treatment and 12 weeks after treatment withdrawal.Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used for statistical analysis.Results Among the 75 patients,51 cases(68.0%)were classified as CKD stage 2,12 cases(16.0%)as CKD stage 3,four cases(5.3%)as CKD stage 4,eight cases(10.7%)as CKD stage 5.Additionally,26 cases(34.7%)were classified as HCV type 3a,while 37 cases(49.3%)were classified as type 3b.Among the patients,51 cases(68.0%)had cirrhosis,including 15(20.0%)compensated cirrhosis and 36(48.0%)decompensated cirrhosis.Twelve weeks after treatment withdrawal,there was a statistically significant improvement in the estimated glomerular filtration rate(eGFR)compared to baseline(81.76(60.94,94.34)mL/(min·1.73 m^(2))vs 70.99(52.86,82.38)mL/(min·1.73 m^(2)),Z=8.12,P=0.040).From baseline to 12 weeks after treatment withdrawal,eGFR of patients with CKD stage 2 and stage 3 were both gradually increased,with statistical significance(H=8.91 and 8.03,respectively,both P<0.05).For CKD stage 2 patients,eGFR increased from 78.82(70.98,84.80)mL/(min·1.73 m^(2))to 86.94(75.91,96.01)mL/(min·1.73 m^(2)),while CKD stage 3 patients had an increased from 51.24(45.92,53.37)mL/(min·1.73 m^(2))to 64.58(44.54,74.34)mL/(min·1.73 m^(2)).Renal function was improved to CKD stage 1 in 21 patients(28.0%).Compared to baseline,CKD stage 2 patients exhibited a decrease of aspartate aminotransferase to platelet ratio index 12 weeks after treatment withdrawal,and alanine aminotransferase and aspartate aminotransferase levels were also significantly improved with statistical significance(Z=8.03,21.57 and 43.74,respectively,all P<0.05).The rate of sustained virological response(SVR)12 at 12 weeks after treatment withdrawal was 98.7%(74/75).Among these cases,51 patients in CKD stage 2,11 patients in CKD stage 3,12 patients in CKD stage 4 and stage 5 reached SVR12.Adverse events occurred in 32 patients(42.7%),including 18 cases of mild hemolytic anemia,four cases of skin itching,three cases of rash,two cases of chest tightness,and five cases of fatigue.Conclusions SOF/VEL with or without ribavirin for the treatment of patients with CHC and CKD has good effectiveness and safety.The renal function,liver function and liver fibrosis degree have been improved after antiviral treatment.