摘要
目的:评估HCV阳性供肾移植给HCV阴性受者并接受索磷布韦(SOF)/维帕他韦(VEL)抗病毒治疗的安全性和有效性，观察移植肾功能及受者预后情况。方法:回顾性分析2019年10月至2021年10月树兰(杭州)医院行肾移植的供受者临床资料，根据是否接受HCV阳性供肾移植将受者分为HCV组(n＝30)和对照组(n＝330)。HCV组受者术后接受SOF/VEL(400/100 mg，1次/d)治疗12周。观察HCV组完成抗病毒治疗后12周HCV RNA阴性受者比例，分析HCV感染或抗病毒治疗相关不良事件。比较两组受者不同时间点血清肌酐、ALT和AST，观察两组受者移植肾功能恢复和生存情况。正态分布计量资料采用成组t检验比较，非正态分布计量资料采用Mann-Whitney U检验比较，计数资料采用χ2检验或Fisher确切概率法比较。采用Kaplan-Meier法绘制两组受者生存曲线，并采用log-rank检验比较生存率。P<0.05为差异有统计学意义。结果:HCV组受者中6例(20.0%)术后检测到HCV RNA，治疗4周后均转阴。在完成抗病毒治疗后12周，HCV组30例(100%)受者均达到SVR，8例(26.7%)受者抗-HCV阳性。HCV组受者均未发生急性排斥反应。1例受者移植肾失功，1例在术后3个月时出现一过性转氨酶升高，6例术后出现白细胞减少，3例发生出血，13例检测到尿多瘤病毒阳性，7例检测到CMV-IgM阳性，1例考虑耶氏肺孢子菌肺炎。上述不良事件均无明确证据表明与HCV感染或抗病毒治疗有关。术后1个月HCV组受者ALT低于对照组[12.0(10.0，18.3)和16.0(11.0，25.0) U/L]，差异有统计学意义(Z＝－2.096，P<0.05)。术后1、3个月HCV组受者AST均低于对照组，差异均有统计学意义(Z＝－3.833和－2.758，P均<0.05)。其余时间点两组受者血清肌酐、ALT和AST差异均无统计学意义(P均>0.05)。截至2022年10月，HCV组受者均存活，对照组死亡4例(1.2%)，两组受者死亡率差异无统计学意义(P>0.05)。HCV组和对照组受者移植肾功能延迟恢复发生率分别为43.3%(13/30)和36.4%(120/330)，移植肾失功发生率分别为3.3%(1/30)和5.8%(19/330)，差异均无统计学意义(χ2＝0.573和0.019，P均>0.05)。HCV组受者术后1、2年累积生存率分别为100%、100%，移植物存活率分别为96.7%、96.7%；对照组受者术后1、2年累积生存率分别为98.8%、98.8%，移植物存活率分别为94.2%、94.2%。两组受者术后2年累积生存率及术后2年移植物存活率差异均无统计学意义(χ2＝0.371和0.333，P均>0.05)。结论:HCV阳性供肾移植给HCV阴性受者并接受SOF/VEL抗病毒治疗安全、有效，移植肾功能及受者预后均良好。
Abstract
Objective:To evaluate the safety and efficacy of transplanting the kidneys from HCV-positive donors to HCV-negative recipients and receiving the antiviral therapy of sofosbuvir (SOF)/velpatasvir (VEL), and to observe the function of transplanted kidneys and prognosis of recipients.Methods:The clinical data of recipients who underwent kidney transplantation in Shulan (Hangzhou) Hospital from October 2019 to October 2021 were retrospectively analyzed. Patients were divided into HCV-positive group (n=30) and control group (n=330) according to whether donors were HCV-positive or not. Patients in the HCV-positive group received the antiviral therapy of SOF/VEL (400/100 mg, once daily) for 12 weeks after surgery. The proportion of HCV RNA-negative recipients in the HCV-positive group 12 weeks after completion of antiviral therapy was observed, and adverse events related to HCV infection or antiviral therapy were analyzed. The serum creatinine, ALT and AST at different time points of the two groups were compared. The recovery of transplanted kidney function and the survival situation of the recipients in the two groups were observed. The measurement data conforming to normal distribution were compared by group t test. Non-normal distribution measurement data were compared by Mann-Whitney U test. The counting data were compared with Chi-square test or Fisher exact test. Kaplan-Meier method was used to draw the survival curve of the two groups, and log-rank test was used to compare the survival rate. A P<0.05 was considered statistically significant.Results:In the HCV-positive group, six recipients (20.0%) were HCV RNA-positive after surgery and all turned negative after 4 weeks of treatment. At 12 weeks after completing antiviral therapy, thirty recipients (100%) in the HCV-positive group achieved SVR and a total of eight recipients (26.7%) were anti-HCV-positive. None of the recipients in the HCV-positive group experienced acute rejection. One patient was allograft renal dysfunction. One patient had transient elevation of aminotransferases at 3 months after surgery. Six patients had leukopenia. Three patients had bleeding. Thirteen cases were positive for uropolyomavirus, seven cases were positive for CMV-IgM, and one case was considered for Pneumocystis jirovecii pneumonia. None of these adverse events had clear evidence of association with HCV infection or antiviral therapy. The ALT level of recipients in the HCV-positive group was lower than that in the control group at one month after surgery [12.0(10.0, 18.3) and 16.0(11.0, 25.0) U/L], and the difference was statistically significant (Z=-2.096, P<0.05). The AST level of recipients in the HCV-positive group at 1 and 3 months after surgery was lower than that in the control group, and the differences were statistically significant (Z=-3.833 and -2.758, all P<0.05). There were no significant differences in serum creatinine, ALT and AST between the two groups at the remaining time points (all P>0.05). Until October 2022, all recipients in the HCV-positive group survived, while four cases (1.2%) died in the control group. There was no significant difference in mortality between the two groups (P>0.05). The incidence rates of delayed graft function in the HCV-positive group and the control group were 43.3% (13/30) and 36.4% (120/330), and the incidence rates of transplanted kidney failure were 3.3% (1/30) and 5.8% (19/330), respectively. The differences were not statistically significant (χ2=0.573 and 0.019, all P>0.05). In the HCV-positive group, the 1- and 2-year cumulative survival rates of recipients were 100% and 100%, respectively, and the transplanted kidneys survival rates were 96.7% and 96.7%, respectively. The 1- and 2-year cumulative survival rates of recipients in the control group were 98.8% and 98.8%, respectively, and the transplanted kidneys survival rates were 94.2% and 94.2%, respectively. There was no significant difference in the 2-year cumulative survival rates of recipients and transplanted kidneys between the two groups (χ2=0.371 and 0.333, all P>0.05).Conclusions:The kidney transplantation from HCV-positive donors to HCV-negative recipients, receiving the antiviral therapy of SOF/VEL, is safe and effective. Moreover, the function of transplanted kidneys and prognosis of recipients are all good.
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