Dataset Information

Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis.

ABSTRACT:

Background

With the development of direct-acting antiviral agents (DAAs), the research on kidney transplantation from Hepatitis C virus (HCV)-viremic donors to HCV-negative recipients has grown. The objective of this comprehensive analysis was to evaluate the efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to negative recipients.

Methods

Multiple databases were searched for a systematic and comprehensive up to March 2022. The primary outcomes included the percentage of sustained virological response at week 12 after the end of treatment (SVR12), adverse events (AEs; any grade), and severe adverse events (SAEs) as the endpoints. Publication bias was examined by using the funnel plots and Egger's test.

Results

In total, 16 studies with 454 subjects were included in the study and the pooled estimate of SVR12, AEs, and SAEs rates were 100.0% (95% CI: 99.2-100.0), 1.9%(95%CI: 0.0-4.9), and 0.0% (95%CI: 0.0-1.5). Subgroup analysis showed that pooled SVR12 rates were 100.0% (95%CI: 99.6-100.0) for genotype (GT)1a and 96.3% (95%CI: 83.3-100.0) for GT2; 100.0% (95%CI: 98.9-100.0) for DAAs treatments; and 100.0% (95%CI: 98.2-100.0) for prophylaxis subgroup. Egger's tests showed that no publication bias was found in this study.

Conclusion

This comprehensive analysis showed the high efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to HCV-negative recipients.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=246541.

SUBMITTER: Feng Z

PROVIDER: S-EPMC9158331 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis.

Feng Zepei Z Zhang Jinwei J Tan Weilong W Wang Chunhui C Chen Qiong Q Shen Chao C Fan Haozhi H Zhang Yun Y Huang Peng P Yue Ming M

Frontiers in medicine 20220518

<h4>Background</h4>With the development of direct-acting antiviral agents (DAAs), the research on kidney transplantation from Hepatitis C virus (HCV)-viremic donors to HCV-negative recipients has grown. The objective of this comprehensive analysis was to evaluate the efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to negative recipients.<h4>Methods</h4>Multiple databases were searched for a systematic and comprehensive up to March 2022. The primary outcomes included ...[more]

PMID: 35665327

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Project description:BackgroundAn increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors.MethodsHCV-uninfected organ recipients without pre-existing liver disease were treated with ezetimibe (10 mg; an HCV entry inhibitor) and glecaprevir-pibrentasvir (300 mg/120 mg) before and after transplantation from HCV-infected donors aged younger than 70 years without co-infection with HIV, hepatitis B virus, or human T-cell leukaemia virus 1 or 2. Recipients received a single dose 6-12 h before transplant and once a day for 7 days after surgery (eight doses in total). HCV RNA was assessed once a day for 14 days and then once a week until 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection, as evidenced by undetectable serum HCV RNA at 12 weeks after transplant, and assessed in the intention-to-treat population. Safety monitoring was according to routine post-transplant practice. 12-week data are reported for the first 30 patients. The trial is registered on ClinicalTrials.gov, NCT04017338. The trial is closed to recruitment but follow-up is ongoing.Findings30 patients (23 men and seven women; median age 61 years (IQR 48-66) received transplants (13 lung, ten kidney, six heart, and one kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5·11 log10IU/mL (IQR 4·55-5·63) and at least three HCV genotypes were represented (nine [50%] donors with genotype 1, two [11%] with genotype 2, five [28%] with genotype 3, and two [11%] with unknown genotype). All 30 (100%) transplant recipients met the primary endpoint of undetectable HCV RNA at 12 weeks post-transplant, and were HCV RNA-negative at last follow-up (median 36 weeks post-transplant [IQR 25-47]). Low-level viraemia was transiently detectable in 21 (67%) of 30 recipients in the early post-transplant period but not after day 14. Treatment was well tolerated with no dose reductions or treatment discontinuations; 32 serious adverse events occurred in 20 (67%) recipients, with one grade 3 elevation in alanine aminotransferase (ALT) possibly related to treatment. Non-serious transient elevations in ALT and creatine kinase during the study dosing period resolved with treatment completion. Among the serious adverse events were two recipient deaths due to causes unrelated to study drug treatment (sepsis at 49 days and subarachnoid haemorrhage at 109 days post-transplant), with neither patient ever being viraemic for HCV.InterpretationEzetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors.FundingCanadian Institutes of Health Research; the Organ Transplant Program, University Health Network.

Project description:Introduction. While use of (hepatitis C virus) HCV-viremic kidneys may result in net benefit for the average end-stage kidney disease (ESKD) patient awaiting transplantation, patients may have different values for ESKD-related health states. Thus, the best decision for any individual may be different depending on the balance of these factors. Our objective was to explore the feasibility of sampling health utilities from hemodialysis patients in order to perform patient-specific decision analyses considering various transplantation strategies. Study Design. We assessed utilities on a convenience sample of hemodialysis patients for health states including hemodialysis, and transplantation with either an HCV-uninfected kidney or an HCV-viremic kidney. We performed patient-specific decision analyses using each patient's age, race, gender, dialysis vintage, and utilities. We used a Markov state transition model considering strategies of continuing hemodialysis, transplantation with an HCV-unexposed kidney, and transplantation with an HCV-viremic kidney and HCV treatment. We interviewed 63 ESKD patients from four dialysis centers (Dialysis Clinic Inc., DCI) in the Cincinnati metropolitan area. Results. Utilities for ESKD-related health states varied widely from patient to patient. Mean values were highest for -transplantation with an HCV-uninfected kidney (0.89, SD: 0.18), and were 0.825 (SD: 0.231) and 0.755 (SD: 0.282), respectively, for hemodialysis and transplantation with an HCV-viremic kidney. Patient-specific decision analyses indicated 37 (59%) of the 63 ESKD patients in the cohort would have a net gain in quality-adjusted life years from transplantation of an HCV-viremic kidney, while 26 would have a net loss. Conclusions. It is feasible to gather dialysis patients' health state utilities and perform personalized decision analyses. This approach could be used in the future to guide shared decision-making discussions about transplantation strategies for ESKD patients.

Project description:BackgroundGiven the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource.ObjectiveTo determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation).DesignOpen-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649).SettingSingle center.Participants10 HCV D+/R- kidney transplant candidates older than 50 years with no available living donors.InterventionTransplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy.MeasurementsThe primary safety outcome was the incidence of adverse events related to GZR-EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis.ResultsAmong 10 HCV D+/R- transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment.LimitationNonrandomized study design and a small number of patients.ConclusionPre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R- kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.Primary funding sourceMerck Sharp & Dohme.

Project description:The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.

Dataset Information

Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis.

Background

Methods

Results

Conclusion

Systematic review registration

Publications

Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis.

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