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
• 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 Female Genotype Hepacivirus Hepatitis C, Chronic Humans Male Middle Aged Pyrrolidines Quinoxalines RNA Viruses Sulfonamides Tissue Donors Transplant Recipients Transplants Viral Load

  More +
• Keywords:
  Buprenorphine Direct-acting Antivirals Ezetimibe Hepatitis C Virus (HCV) Methadone Mortality Naltrexone Organ Transplantation Prevention 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
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:61c1ad7b4f84dce66fbd50cb5a47e311b6104e7fee8fbfa408798bc9ce1eca1882c18b69c1d7213829245237aabd9cafe9caf4174b007eb8652786b42cf1f7bc
• Download URL:
  https://stacks.cdc.gov/view/cdc/103491/cdc_103491_DS1.pdf
• File Type:
  [PDF - 593.38 KB ]