Prospective Multicenter Study of Early Antiviral Therapy in Liver and Kidney Transplant Recipients of HCV‐Viremic Donors

Terrault, Norah A.; Burton, James R.; Ghobrial, R. Mark; Verna, Elizabeth C.; Bayer, Johanna; Klein, Christina L.; Victor, David W.; Mohan, Sumit; Trotter, James F.; Dodge, Jennifer L.; Niemann, Claus U.; Rubin, Raymond A.

doi:10.1002/hep.31551

Cited by 35 publications

(66 citation statements)

References 21 publications

(34 reference statements)

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“…Our initial search terms resulted in a set of 2186 articles, of which 35 studies satisfied the inclusion and exclusion criteria (Figure 1), 13‐46 including one paper identified with reference search 47 . There were 852 SOTs, which included 343 kidney, 233 heart, 204 liver and 72 lung transplants.…”

Section: Resultsmentioning

confidence: 99%

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Systematic review: hepatitis C viraemic allografts to hepatitis C‐negative recipients in solid organ transplantation

Raasikh

Jamali

Flores

et al. 2021

Aliment Pharmacol Ther

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Summary Background Given the success of direct‐acting antivirals (DAAs) in treating hepatitis C (HCV), interest is growing in utilizing solid organs from allografts with active HCV to expand donor availability. Aim To review post‐transplant outcomes and patient survival in HCV‐negative recipients receiving solid organ transplants (SOT) from viraemic, that is, HCV+/NAT+ (nucleic acid testing) allografts. Methods A literature search was conducted on PubMed and EMBASE from 01/01/2007 to 4/17/2021 for articles matching eligibility criteria. Two authors independently screened titles and abstracts. Disagreements were solved by a third independent reviewer. Methodological quality assessment was done using a modified Newcastle‐Ottawa scale (NOS). Data synthesis was done qualitatively using median, ranges and percentages. Results Thirty‐five studies were included (or 852 SOTs): 343 kidney, 233 heart, 204 liver, and 72 lung transplants from viraemic allografts. Of the recipients eligible for sustained virological response at 12 weeks (SVR12) calculation, 100% achieved cure from HCV. No deaths/graft failures were reported to be related to HCV transmission. Seven SOT recipients had viral relapse, with all seven patients treated successfully. Four patients developed fibrosing cholestatic hepatitis with complete resolution post‐treatment. Conclusions Transplanting viraemic organs into uninfected individuals can become the standard of care for patients who do not have contraindications to DAAs.

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Section: Resultsmentioning

confidence: 99%

“…The remaining two studies had the hospital cover the cost of DAA treatment if personal insurance was unable to, 47 and the other study had costs of DAAs covered through research funds (Table S3). 44 …”

Section: Resultsmentioning

confidence: 99%

Systematic review: hepatitis C viraemic allografts to hepatitis C‐negative recipients in solid organ transplantation

Raasikh

Jamali

Flores

et al. 2021

Aliment Pharmacol Ther

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“…Regimens provided with safety and efficacy towards all HCV genotypes, even in patients with advanced CKD, should be adopted. Overall, a total of 201 kidney transplants were collected ( Table 3 ); as listed in Table 3 and Table 4 , the majority of the reports had high efficacy and safety [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. However, some studies were externally funded, and this is a source of bias [ 48 ].…”

Section: Kidney Transplant From Hcv-positive/nat-positive (Hcv Rna-positive) Donors In Naïve Recipientsmentioning

confidence: 99%

“…Most individuals ( n = 21) who completed the 24 weeks of observation period achieved SVR24. No serious adverse events occurred [ 47 ].…”

Section: Kidney Transplant From Hcv-positive/nat-positive (Hcv Rna-positive) Donors In Naïve Recipientsmentioning

confidence: 99%

“…Nonetheless, pre-emptive and prophylactic approaches are two strategies that are not easily reproducible in the “real-world” where access to DAAs can be biased by barriers such as insurance approval. Many studies reported in Table 3 and Table 4 received funding [ 38 , 39 , 40 , 42 , 43 , 47 ] and did not generate “real-world” evidence. It is difficult to understand whether some AEs were related to the transmission of HCV infection, use of DAAs, or kidney transplant per se.…”

Section: Kidney Transplant From Hcv/nat-positive Donors To Naïve Recipients: Pros and Consmentioning

confidence: 99%

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Updated View on Kidney Transplant from HCV-Infected Donors and DAAs

2021

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Background: The discrepancy between the number of potential available kidneys and the number of patients listed for kidney transplant continues to widen all over the world. The transplant of kidneys from hepatitis C virus (HCV)-infected donors into HCV naïve recipients has grown recently because of persistent kidney shortage and the availability of direct-acting antiviral agents. This strategy has the potential to reduce both waiting times for transplant and the risk of mortality in dialysis. Aim: We made an extensive review of the scientific literature in order to review the efficacy and safety of kidney transplant from HCV-viremic donors into HCV naïve recipients who received early antiviral therapy with direct-acting antiviral agents (DAAs). Results: Evidence has been rapidly accumulated on this topic and some reports have been published (n = 11 studies, n = 201 patients) over the last three years. Various combinations of DAAs were administered—elbasvir/grazoprevir (n = 38), glecaprevir/pibrentasvir (n = 110), and sofosbuvir-based regimens (n = 53). DAAs were initiated in a range between a few hours before renal transplant (RT) to a median of 76 days after RT. The sustained virological response (SVR) rate was between 97.5% and 100%. A few severe adverse events (SAEs) were noted including fibrosing cholestatic hepatitis (n = 3), raised serum aminotransferase levels (n = 11), and acute rejection (n = 7). It remains unclear whether the AEs were related to the transmission of HCV, the use of DAAs, or kidney transplant per se. It appears that the frequency of AEs was greater in those studies where DAAs were not given in the very early post-kidney transplant phase. Conclusions: The evidence gathered to date encourages the expansion of the kidney donor pool with the adoption of HCV-infected donor organs. We suggest that kidney transplants from HCV-viremic kidneys into HCV-uninfected recipients should be made in the context of research protocols. Many of the studies reported above were externally funded and we need research generating “real-world” evidence. The recent availability of pangenotypic combinations of DAAs, which can be given even in patients with eGFR < 30/min/1.73 m2, will promote the notion that HCV-viremic donors are a significant resource for kidney transplant.

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A systematic review of direct acting antiviral therapies in hepatitis C virus‐negative liver transplant recipients of hepatitis C‐viremic donors

et al. 2022

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The introduction of safe and highly effective direct acting antivirals (DAAs) has significantly improved hepatitis C virus (HCV) treatment outcomes after transplant. The solid organ transplant community has sought to identify strategies aimed at increasing the donor pool including the utilization of HCV‐viremic organs in HCV‐negative recipients. We will review the existing literature to evaluate DAA use for the treatment of HCV viremia post‐liver transplant in patients who receive HCV‐viremic allografts. A PubMed search was conducted and references for each study were also reviewed to identify additional articles. Randomized controlled trials, cohort studies, case series, and case reports were included if: published in English language, evaluated DAA treatment outcomes after liver only or simultaneous liver‐kidney transplantation with HCV‐viremic allografts in HCV‐negative recipients, and had full‐text article availability. Our review included 16 studies and 2 case reports. The majority of liver transplant recipients were treated with a pangenotypic DAA for 12 weeks with a heterogeneous median time to initiation (range 1.7–118 days). Sustained virologic response was assessed in 253 liver transplant patients with 99.6% achieving cure with minimal DAA‐attributed adverse drug events. There were 23 reported episodes of rejection, 12 deaths, and 1 graft loss among all studies. Treatment with DAA after transplantation of HCV‐viremic livers into HCV‐negative recipients appears to be safe and effective; however, long‐term outcomes remain unknown. Transplant pharmacists play a key role in the development of center‐specific protocols to optimize post‐transplant outcomes in this unique patient population.

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Prospective Multicenter Study of Early Antiviral Therapy in Liver and Kidney Transplant Recipients of HCV‐Viremic Donors

Cited by 35 publications

References 21 publications

Systematic review: hepatitis C viraemic allografts to hepatitis C‐negative recipients in solid organ transplantation

Systematic review: hepatitis C viraemic allografts to hepatitis C‐negative recipients in solid organ transplantation

Updated View on Kidney Transplant from HCV-Infected Donors and DAAs

A systematic review of direct acting antiviral therapies in hepatitis C virus‐negative liver transplant recipients of hepatitis C‐viremic donors

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