Curing Hepatitis C Virus (HCV) Infection in a Heart and Kidney Transplant Recipient with Direct Acting Antiviral (DAA) Therapy: A Novel Case Report

Abstract

Introduction: The estimated HCV infection prevalence is 8.9-31.6% and 2% respectively in kidney (KT) and heart transplant (HT) recipients. Progression of HCV infection after organ transplantation (txp) adversely impacts graft and patient (pt) survival. HCV treatment (Rx) in solid organ txp pts with interferon (IFN) and ribavirin has been limited by low efficacy, intolerable side effects and risk for IFN-induced graft rejection. All-oral DAA Rx is highly efficacious and well-tolerated in non-txp and liver txp pts. Data are limited on DAA Rx in non-liver solid organ txp pts. Here we report a case of a KT and HT recipient successfully treated for HCV with sofosbuvir/ledipasvir (SOF/LDV). Case description: A 32-year-old female who had orthotopic HT in 1988 for viral cardiomyopathy, KT in 2000 for cyclosporine nephrotoxicity, hypertension and headache was diagnosed with HCV infection during KT workup. At the time, liver biopsy showed minimal fibrosis. She deferred IFN Rx, and re-presented for HCV Rx in 2015. She denied symptoms or complications of liver disease. Pt was on tacrolimus, mycophenolate mofetil, prednisone, aspirin, atenolol, pravastatin, amitriptyline and an oral contraceptive. Exam revealed no signs of chronic liver or heart disease, and benign abdomen. Baseline labs: HCV RNA 986,000 IU/mL, genotype 1b, ALT 21, AST 23, ALP 62, Alb 3.6, TB 0.5, WBC 8K, Hgb 12.1, Plt 304K, Cr 1.36 (GFR 45), no proteinuria, and INR 0.9. US abdomen showed normal liver. FibroScan was 3.5 kPa. She was treated with SOF/LDV for 12 wks. HCV RNA was undetectable at wk 4 of Rx, end of Rx and 12 wks post-Rx (i.e. SVR12). Liver and kidney function and tacrolimus level remained stable. She reported headache and fatigue at Rx onset, but overall tolerated Rx well without evidence of organ rejection. Discussion: In contrast to IFN and ribavirin, which act as immunomodulators, the 3 major classes of DAA Rx - inhibitors of the NS3/4A protease, NS5A replication complex and NS5B polymerase - act directly on HCV binding sites, making DAAs more potent and well-tolerated than IFN-based Rx. The lack of drug interactions with immunosuppressants reduces risk of graft rejection. To our knowledge, this is the first report of a HT and KT recipient treated successfully with SOF/LDV. Successful Rx in this pt population will improve survival, reduce morbidity, and may expand HT listing criteria to include HCV pts and increase utilization of high-risk donor organs to reduce waitlist mortality.