Safety and efficacy of current direct‐acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV‐TARGET study

Saxena, Varun; Khungar, Vandana; Verna, Elizabeth C.; Levitsky, Josh; Brown, Robert S.; Hassan, Mohamed A.; Sulkowski, Mark S.; O’Leary, Jacqueline G.; Koraishy, Farrukh M.; Galati, Joseph; Kuo, Alexander; Vainorius, Monika; Akushevich, Lucy; Nelson, David R.; Fried, Michael; Terrault, Norah A.; Reddy, K. Rajender

doi:10.1002/hep.29258

Cited by 155 publications

(137 citation statements)

References 23 publications

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“…Despite this, HCV-positive organs continue to be discarded at higher rates than HCV-negative organs of similar quality (14, 34–37). Because direct- acting antivirals are now widely available to cure HCV infection, including in transplant recipients (38–40), organs from infected donors should be considered more broadly. In 2 recent single-center pilot trials (41, 42), kidneys from HCV-infected donors were successfully used for transplant in uninfected recipients in combination with direct-acting antivirals.…”

Section: Discussionmentioning

confidence: 99%

The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States

et al. 2018

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Background: The epidemic of drug overdose deaths in the United States has led to an increase in organ donors. Objective: To characterize donors who died of overdose and to analyze outcomes among transplant recipients. Design: Prospective observational cohort study. Setting: Scientific Registry of Transplant Recipients, 1 January 2000 to 1 September 2017. Participants: 138 565 deceased donors; 337 934 transplant recipients at 297 transplant centers. Measurements: The primary exposure was donor mechanism of death (overdose-death donor [ODD], trauma-death donor [TDD], or medical-death donor [MDD]). Patient and graft survival and organ discard (organ recovered but not transplanted) were compared using propensity score-weighted standardized risk differences (sRDs). Results: A total of 7313 ODDs and 19 897 ODD transplants (10 347 kidneys, 5707 livers, 2471 hearts, and 1372 lungs) were identified. Overdose-death donors accounted for 1.1% of donors in 2000 and 13.4% in 2017. They were more likely to be white (85.1%), aged 21 to 40 years (66.3%), infected with hepatitis C virus (HCV) (18.3%), and increased-infectious risk donors (IRDs) (56.4%). Standardized 5-year patient survival was similar for ODD organ recipients compared with TDD organ recipients (sRDs ranged from 3.1% lower to 3.9% higher survival) and MDD organ recipients (sRDs ranged from 2.1% to 5.2% higher survival). Standardized 5-year graft survival was similar between ODD and TDD grafts (little difference for kidneys and lungs, marginally lower [sRD, −3.2%] for livers, and marginally higher [sRD, 1.9%] for hearts). Kidney discard was higher for ODDs than TDDs (sRD, 5.2%) or MDDs (sRD, 1.5%); standardization for HCV and IRD status attenuated this difference. Limitation: Inability to distinguish between opioid and nonopioid overdoses. Conclusion: In the United States, transplantation with ODD organs has increased dramatically, with noninferior outcomes in transplant recipients. Concerns about IRD behaviors and hepatitis C among donors lead to excess discard that should be minimized given the current organ shortage.

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Section: Discussionmentioning

confidence: 99%

The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States

et al. 2018

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“…However, the landscape of HCV changed in 2013 with the introduction of direct-acting antiviral (DAAs) with high cure rates even in KT. (13–17) In 2015, the once daily fixed-dose combination of the NS3/4A protease inhibitor grazoprevir (GZR) and the NS5A inhibitor elbasvir (EBR) was approved for use in individuals with impaired renal function and HCV genotype 1a infection. (18) For genotype 2 and 3 infection, the NS5B inihibitor sofosbuvir (SOF) is highly active (19).…”

Section: Introductionmentioning

confidence: 99%

Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus–Infected Donors to Noninfected Recipients

et al. 2018

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Background Given the high mortality rate for those with end-stage kidney d sease on dialysis and the efficacy and safety of current hepatitis C virus (HCV) treatments, currently-discarded kidneys from HCV-infected (HCV+) donors may be a neglected public health resource. Objective To determine the tolerability and feasibility of kidney transplantation (KT) from HCV+ donors to HCV-uninfected recipients (HCV D+/R−) in combination with direct-acting antivirals (DAAs) as pre- and post-transplant prophylaxis. Design Open-label, non-randomized trial. (ClinicalTrials.gov: NCT02781649) Setting Single-center. Participants 10 HCV-uninfected KT candidates over the age of 50 years with no available living donors. Intervention KT from deceased donors ages 13–50 years with a positive HCV RNA and HCV antibody test. All recipients received a dose of grazoprevir 100 mg/elbasvir 50 mg (GZR/EBR) immediately prior to transplant. For genotype 1 donors, recipients continued GZR/EBR for 12 weeks post-transplant; for genotype 2 or 3 donors, sofosbuvir 400 mg was added to GZR/EBR for 12 weeks of triple-therapy. Measurements The primary safety outcome was the incidence of adverse events related to GZR-EBR. The primary efficacy outcome was the proportion recipients with HCV RNA less than the lower limit of quantification 12 weeks after prophylaxis. Results Among 10 HCV D+/R− there were no treatment-related adverse events and HCV RNA was not detected in any recipient 12 weeks after treatment. Limitations Nonrandomized study design and small number of patients. Conclusions Pre- and post-transplant HCV treatment was safe and prevented chronic hepatitis C in HCV D+/R− KT. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for HCV− KT candidates.

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“…The therapeutic success increased significantly to 95%-97% Sustained Viral Response (SVR) depending on the fibrosis stage and cirrhosis [5][6][7][8][9]. Therefore a necessity of earlier diagnosis became indubitable to prevent the future complications and deaths.…”

Section: Introductionmentioning

confidence: 99%

Screening and diagnosis of chronic HCV infection in Bulgaria: A review of the current practice

Dimitrova¹,

Kamusheva²,

Mitov³

et al. 2018

biomedicalresearch

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Background: Chronic HCV infection is one of the leading causes of chronic liver disease and places significant health and economic burden worldwide. In Bulgaria blood and blood products weren`t screened before 1992. Currently there is no official national screening program and diagnosis is usually accidental and in more advanced stages of the disease. Methods and materials: A synthetic, population-based decision tree with Markov chain model compares the current practice (No screening) with possible screening program among (Screening) the people aged 39-64 as a part of the routine prophylaxis program. A Markov chain model was built at the end every decision node of the patients without Sustained Viral Response (SVR) to find how they will progress for the observed period. Results: Possible national screening would lead to almost 4 times higher number of patients diagnosed at early stages of the infection, almost 2 to 4 times higher number of patients with access to treatment and decrease in the HCV-related expected mortality. Expected life years gained in the Screening alternative are almost 2 (10 417 LYGs) and 4 times (22 715 LYGs) higher compared to the current situation (4798 LYGs), respectively. Only 45% of the people however perform routine prophylaxis. Conclusion: National screening is considered as effective health care measure to fight chronic diseases because through active search we can find asymptomatic patients. Initiation of treatment in early stages of hepatitis C infection is more effective and decreases the mortality rates.

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Safety and efficacy of current direct‐acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV‐TARGET study

Cited by 155 publications

References 23 publications

The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States

The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States

Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus–Infected Donors to Noninfected Recipients

Screening and diagnosis of chronic HCV infection in Bulgaria: A review of the current practice

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