benzofurans and End-Stage-Liver-Disease

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.. 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.. Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897).. Single center.. 20 HCV-negative transplant candidates.. Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir-grazoprevir on posttransplant day 3.. 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.. 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).. Small trial.. 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.. Merck.

Topics: Antiviral Agents; Benzofurans; Creatinine; Drug Combinations; End Stage Liver Disease; Female; Genotype; Glomerular Filtration Rate; Hepacivirus; Hepatitis C; Humans; Imidazoles; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Quality of Life; Quinoxalines; RNA, Viral; Tissue Donors; Treatment Outcome; Viral Load

Current national hepatitis C virus (HCV) guidelines do not recommend the use of elbasvir (EBR)/grazoprevir (GZR) in postliver transplantation (LT) patients due to drug-drug interactions with immunosuppression agents. However, recommendations do not address the treatment of HCV in renally impaired post-LT patients. Treatment regimens that are recommended for post-LT patients are not safe in patients with severe renal impairment and patients on dialysis. EBR/GZR is approved for use in patients with renal impairment and patients on dialysis, but not in the post-LT setting.. Authors reviewed the electronic medical records of 3 treatment-naive HCV genotype 1a male post-LT patients on hemodialysis who were treated with EBR/GZR with or without ribavirin for 12 or 16 weeks.. No patients had serious adverse drug events during treatment and no patients stopped treatment early or died. Providers monitored immunosuppression levels; both patients who were taking tacrolimus required immunosuppression dose adjustments during HCV treatment. No patients experienced organ rejection. All patients achieved sustained virologic response.. Current HCV guidelines do not address the treatment options for post-LT patients with severe renal impairment or who are on dialysis, nor do published accounts of use of EBR/GZR in this patient population exist. Clinicians may benefit from exposure to real-world cases of HCV treatment in this historically difficult-to-cure patient population. Providers must address drug-drug interactions with EBR/GZR and monitor for changes in immunosuppression levels to ensure safety with its use in post-LT patients.

Topics: Academic Medical Centers; Aged; Antiviral Agents; Benzofurans; Drug Combinations; Drug Interactions; Drug Monitoring; Electronic Health Records; End Stage Liver Disease; Graft Rejection; Graft Survival; Hepatitis C, Chronic; Humans; Imidazoles; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Quinoxalines; Renal Dialysis; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome