Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients: A Single-Group Trial

Ann Intern Med. 2018 Sep 4;169(5):273-281. doi: 10.7326/M18-0749. Epub 2018 Aug 7.

Abstract

Background: Organs from hepatitis C virus (HCV)-infected deceased donors are often discarded. Preliminary data from 2 small trials, including THINKER-1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), suggested that HCV-infected kidneys could be safely transplanted into HCV-negative patients. However, intermediate-term data on quality of life and renal function are needed to counsel patients about risk.

Objective: To describe 12-month HCV treatment outcomes, estimated glomerular filtration rate (eGFR), and quality of life for the 10 kidney recipients in THINKER-1 and 6-month data on 10 additional recipients.

Design: Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897).

Setting: Single center.

Participants: 20 HCV-negative transplant candidates.

Intervention: Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir-grazoprevir on posttransplant day 3.

Measurements: The primary outcome was HCV cure. Exploratory outcomes included 1) RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) quality-of-life scores at enrollment and after transplant, and 2) posttransplant renal function, which was compared in a 1:5 matched sample with recipients of HCV-negative kidneys.

Results: The mean age of THINKER participants was 56.3 years (SD, 6.7), 70% were male, and 40% were black. All 20 participants achieved HCV cure. Hepatic and renal complications were transient or were successfully managed. Mean PCS and MCS quality-of-life scores decreased at 4 weeks; PCS scores then increased above pretransplant values, whereas MCS scores returned to baseline values. Estimated GFRs were similar between THINKER participants and matched recipients of HCV-negative kidneys at 6 months (median, 67.5 vs. 66.2 mL/min/1.73 m2; 95% CI for between-group difference, -4.2 to 7.5 mL/min/1.73 m2) and 12 months (median, 72.8 vs. 67.2 mL/min/1.73 m2; CI for between-group difference, -7.2 to 9.8 mL/min/1.73 m2).

Limitation: Small trial.

Conclusion: Twenty HCV-negative recipients of HCV-infected kidneys experienced HCV cure, good quality of life, and excellent renal function. Kidneys from HCV-infected donors may be a valuable transplant resource.

Primary funding source: Merck.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use
  • Benzofurans / therapeutic use
  • Creatinine / blood
  • Drug Combinations
  • End Stage Liver Disease / complications
  • End Stage Liver Disease / physiopathology
  • End Stage Liver Disease / surgery*
  • Female
  • Genotype
  • Glomerular Filtration Rate
  • Hepacivirus / genetics
  • Hepatitis C* / drug therapy
  • Humans
  • Imidazoles / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Quality of Life
  • Quinoxalines / therapeutic use
  • RNA, Viral / blood
  • Tissue Donors*
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Benzofurans
  • Drug Combinations
  • Imidazoles
  • Immunosuppressive Agents
  • Quinoxalines
  • RNA, Viral
  • elbasvir-grazoprevir drug combination
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT02743897