Dataset Information

Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C-Viremic Donor to Uninfected Recipient Kidney Transplantation.

ABSTRACT:

Introduction

Long wait times for kidney transplants have prompted investigation into strategies to decrease the discarding of potentially viable organs. Recent reports suggest that kidneys from hepatitis C virus (HCV)-infected donors may be transplanted into HCV-naive donors followed by direct-acting antiviral therapy.

Methods

This was a pilot clinical trial to transplant kidneys from HCV-infected donors into HCV-naive recipients with preemptive use of elbasvir and grazoprevir for 12 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy. Secondary outcomes were safety, quality of life, and early viral kinetics.

Results

A total of 33 patients were screened, and 8 underwent kidney transplantation from a HCV-viremic donors from August 2017 to March 2019. The median donor kidney donor profile index was 31% (range, 29%-65%), and patients who underwent transplantation waited a median of 6.5 months (range, 1-19 months). None had detectable HCV viremia beyond 2 weeks post-transplantation, and all achieved sustained virologic response 12 weeks after therapy (SVR12). There were no study-related severe adverse events. One patient experienced early graft loss due to venous thrombosis, whereas the remaining 7 patients had excellent allograft function at 6 months.

Conclusion

Preemptive elbasvir and grazoprevir eliminated HCV infection in HCV-naive patients who received a kidney transplant from an HCV-infected donor.

SUBMITTER: Sise ME

PROVIDER: S-EPMC7136432 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C-Viremic Donor to Uninfected Recipient Kidney Transplantation.

Sise Meghan E ME Strohbehn Ian A IA Chute Donald F DF Gustafson Jenna J Van Deerlin Vivianna M VM Smith Jennifer R JR Gentile Caren C Wojciechowski David D Williams Winfred W WW Elias Nahel N Chung Raymond T RT

Kidney international reports 20200113 4

<h4>Introduction</h4>Long wait times for kidney transplants have prompted investigation into strategies to decrease the discarding of potentially viable organs. Recent reports suggest that kidneys from hepatitis C virus (HCV)-infected donors may be transplanted into HCV-naive donors followed by direct-acting antiviral therapy.<h4>Methods</h4>This was a pilot clinical trial to transplant kidneys from HCV-infected donors into HCV-naive recipients with preemptive use of elbasvir and grazoprevir for ...[more]

PMID: 32280841

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Project description:Background:There is a low utilization rate of donated donor lungs. Historically, transplantation of lungs from hepatitis C-viremic donors to hepatitis C (HCV) negative recipients was avoided due to concern for worse graft survival. In the past few years with the advent of direct acting antiviral (DAA) therapy, there are emerging data suggesting the safety and efficacy of transplanting thoracic organs from HCV-viremic donors. This study assessed the differences in donor characteristics and allograft-specific clinical features at the time of organ offer and investigated whether these variables differed in HCV-viremic versus HCV-negative donors and impacted recipient outcomes. Methods:We conducted a single-center, retrospective cohort study of adult patients who underwent a lung transplant at Brigham and Women's Hospital between March 2017 and October 2018. Patients were stratified based on their donor HCV status (HCV-viremic versus HCV-negative). Donor and allograft-specific characteristics and clinical features including chest imaging and bronchoscopy reports, respiratory cultures, and the donor's oxygenation as measured by the arterial partial pressure of oxygen (PaO2) were collected as well as recipient baseline characteristics and transplant outcomes. Results:During the study period, 42 and 57 lung transplants were performed from HCV-viremic and HCV-negative donors, respectively. Donor age was similar in both cohorts. More HCV-viremic donors died from drug intoxication (71% versus 19%, P=0.0001) and had a history of cigarette use (83% versus 5%, P=0.0001) and drug use (76% versus 49%, P=0.007). There were differences in the baseline recipient characteristics including a lower median lung allocation score in the HCV-viremic cohort. The organ-specific clinical characteristics including the terminal PaO2, chest imaging and bronchoscopy findings, and evidence of pulmonary infection were similar between the two cohorts. The recipient outcomes overall were excellent and did not differ significantly in both cohorts in terms of graft and patient survival at 6 and 12 months. Conclusions:Despite a greater proportion of HCV-viremic donors being increased risk with a history of drug and cigarette use and having died as a result of drug intoxication, the quality of the HCV-viremic donor organs did not differ from the HCV-negative donor organs or impact graft and recipient survival. Due to an increasing number of transplants from increased risk donors and in order to develop safe and effective protocols to perform lung transplants from HCV-infected donors, further characterization of the donor and allograft-specific clinical features and longer-term recipient outcomes is greatly needed.

Project description:PurposePeople chronically infected with hepatitis C virus (HCV) have diminished patient-reported outcomes (PROs). This study aimed to compare the impact of elbasvir/grazoprevir (EBR/GZR) treatment versus sofosbuvir with pegylated interferon and ribavirin (SOF/PR) on changes in PROs: 1) during the treatment period and 2) at posttreatment follow-up.Patients and methodsPRO data collected during the Phase III C-EDGE Head-2-Head (H2H) open-label study was analyzed. In this trial, patients infected with HCV were randomized 1:1 to receive either EBR/GZR or SOF/PR for 12 weeks. Patients self-administered the Short Form-36 version 2 (SF-36v2®) Health Survey Acute (1-week recall) Form and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at baseline, during treatment, and posttreatment. Between-group differences in mean change of PRO scores from baseline were estimated during the treatment period and also at the posttreatment follow-up. Effect sizes were calculated to evaluate if the detected change in mean PRO scores is clinically meaningful between groups.ResultsThere were 255 patients (99.2% White, 54.1% female, 74.9% treatment naïve) included in the analysis. During the treatment period, significant declines in SF-36v2 scores were observed across all domains for the SOF/PR group. Compared to the SOF/PR group, the EBR/GZR group reported more improvement in scores across all SF-36v2 domain scores at the end of the treatment period. At treatment week 12, the between-group differences for 6 out of the 8 domain scores for these patients reflected at least moderate effects (effect sizes >0.5). No significant between-group differences in change in SF-36v2 scores from baseline were detected posttreatment. The decline in SF-36v2 scores observed during the treatment period for the SOF/PR group returned to near baseline scores or above posttreatment. Treatment with EBR/GZR did not impact fatigue scores, but treatment with SOF/PR led to increased fatigue scores during treatment which resolved by posttreatment follow-up week 12.ConclusionThis study demonstrated that HCV treatment with EBR/GZR resulted in a significantly better PRO profile as compared to SOF/PR. PROs are an important consideration as worsening PROs experienced during treatment may negatively influence adherence and ultimately contribute to an unfavorable clinical outcome.Clinicaltrialsgov identifierNCT02358044.

Project description:ObjectiveThis study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the reporting quality and to summarize the results.MethodsA literature search was undertaken using Medline, Embase, the Cochrane Library, EconLit, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP to identify original articles containing economic evaluations of EBR/GZR for CHC published between 1 January 2000 and 31 December 2020. The Consolidated Health Economic Evaluation Reporting Standards statement was used to assess the quality of reporting of the articles.ResultsOf 93 articles identified, 13 studies fulfilled the inclusion criteria. These studies were conducted in 4 countries, and 8 active interventions were assessed. The target population was patients infected with CHC genotype 1 infection in all studies. Eight out of 13 studies that compared EBR/GZR vs. other direct antiviral agents suggested that EBR/GZR was generally more cost-effective or dominant than daclatasvir/asunaprevir (DCV/ASV), sofosbuvir/velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir (3D) but not more cost-effective than glecaprevir/pibrentasvir (GLE/PIB). Two studies from China and one study from the USA that compared EBR/GZR vs. pegylated interferon and ribavirin (PegIFN/RBV) consistently indicated that EBR/GZR was generally more cost-effective than PegIFN/RBV. One study from Italy compared EBR/GZR with SOF + PegIFN/RBV and suggested that EBR/GZR had a lower cost and higher effectiveness. One study from France and one study from the USA confirmed that compared with non-therapy for patients with chronic kidney disease, EBR/GZR was cost-effective at commonly accepted current standards. All included studies were of good quality of reporting, with an average score of 21.9 (range 19-23).ConclusionEBR/GZR for CHC genotype 1 might be cost-effective or dominant compared with PegIFN/RBV and other direct antiviral agents (SOF/VEL, 3D, DCV/ASV, LDF/SOF) or non-therapy. However, under certain assumptions, EBR/GZR was not a cost-effective alternative for CHC patients vs. GLE/PIB.

Dataset Information

Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C-Viremic Donor to Uninfected Recipient Kidney Transplantation.

Introduction

Methods

Results

Conclusion

Publications

Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C-Viremic Donor to Uninfected Recipient Kidney Transplantation.

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