Evaluation of short-course direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: A single-centre, open-label study

Details

• Alternative Title:
  Lancet Gastroenterol Hepatol
• Personal Author:
  Feld, Jordan J ; Cypel, Marcelo ; Kumar, Deepali ; Dahari, Harel ; Ribeiro, Rafaela Vanin Pinto ; Marks, Nikki ; Kamkar, Nellie ; Bahinskaya, Ilona ; Onofrio, Fernanda Q ; Zahoor, Mohamed A ; Cerrochi, Orlando ; Tinckam, Kathryn ; Kim, S Joseph ; Schiff, Jeffrey ; Reichman, Trevor W ; McDonald, Michael ; Alba, Carolina ; Waddell, Thomas K ; Sapisochin, Gonzalo ; Selzner, Markus ; Keshavjee, Shaf ; Janssen, Harry LA ; Hansen, Bettina E ; Singer, Lianne G ; Humar, Atul
  More +
• Description:
  Background ; An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). 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 antivirals 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. ; Methods ; HCV-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 one dose before and daily for 7 days after transplantation from HCV-infected donors under age 70 without HIV or HBV co-infection. HCV RNA was assessed daily for 14 days and then weekly to 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection by intention-to-treat as evidenced by undetectable serum HCV RNA 12 weeks after transplant (registration NCT04017338). ; Findings ; 30 patients (23 male, median age 61) received transplants (13 lung, 10 kidney, 6 heart and 1 kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5.11 log10IU/mL (range 1.18–7.13, IQR 4.55–5.63 log10IU/mL) and included different HCV genotypes (9 genotype 1, 2 genotype 2, 5 genotype 3 and 2 genotype unknown). All 30 of 30 (100%) patients met the primary endpoint with undetectable HCV RNA at 12 weeks post-transplant and remain HCV RNA negative at last follow-up (median 36 weeks, range 14–54, IQR 25–47 weeks post-transplant). Low-level viremia was transiently detectable in 20 (67%) of 30 recipients in the early post-transplant period but never beyond day 11. Treatment was well tolerated with no dose reductions or treatment discontinuations; there were 27 serious adverse events in 18 (60%) of 30 patients with one grade 3 ALT elevation possibly related to treatment. Transient ALT and CK elevations during treatment resolved with treatment completion. Two recipients died of unrelated causes and neither was ever viremic for HCV. ; Interpretation ; Ezetimibe combined with glecaprevir/pibrentasvir given one dose before and for 7 days after transplant prevented establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study demonstrates that an ultra-short course of DAAs and ezetimibe can prevent establishment of chronic HCV infection in the recipient, alleviating many of the concerns of using HCV-infected organs for transplantation.
• Subjects:
  • Adult
  • Aged
  • Anticholesteremic Agents
  • Antiviral Agents
  • Benzimidazoles
  • Canada
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Ezetimibe
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• Keywords:
  • organ transplantation
  • hepatitis C virus (HCV)
  • prevention
  • ezetimibe
  • direct-acting antivirals
  • Naltrexone
  • Buprenorphine
  • Methadone
  • Mortality
  • Treatment
• Source:
  Lancet Gastroenterol Hepatol. 5(7):649-657
• Pubmed ID:
  32389183
• Pubmed Central ID:
  PMC7391837
• Document Type:
  Journal Article
• Funding:
  U01 AI063594–11/AI/NIAID NIH HHSUnited States/ ; R01 AI144112/AI/NIAID NIH HHSUnited States/ ; U01 AI063594/AI/NIAID NIH HHSUnited States/ ; U01 DK082874/DK/NIDDK NIH HHSUnited States/ ; R01 AI078881/AI/NIAID NIH HHSUnited States/ ; U51 PS004607/PS/NCHHSTP CDC HHSUnited States/ ; I01 CX001398/CX/CSRD VAUnited States/ ; R01 GM121600/GM/NIGMS NIH HHSUnited States/ ; R01 AI146917/AI/NIAID NIH HHSUnited States/
• Volume:
  5
• Issue:
  7
• Download URL:
  https://stacks.cdc.gov/view/cdc/103491/cdc_103491_DS1.pdf
• File Type:
  [PDF - 593.38 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:61c1ad7b4f84dce66fbd50cb5a47e311b6104e7fee8fbfa408798bc9ce1eca1882c18b69c1d7213829245237aabd9cafe9caf4174b007eb8652786b42cf1f7bc