Increased early acute cellular rejection events in hepatitis C-positive heart transplantation

• Published in: The Journal of heart and lung transplantation Vol. 39; no. 11; pp. 1199 - 1207
• Main Authors: Gidea, Claudia G., Narula, Navneet, Reyentovich, Alex, Fargnoli, Anthony, Smith, Deane, Pavone, Jennifer, Lewis, Tyler, Karpe, Hannah, Stachel, Maxine, Rao, Shaline, Moreira, Andre, Saraon, Tajinderpal, Raimann, Jochen, Kon, Zachary, Moazami, Nader
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: Acute Disease; Adult; Aged; direct-acting antivirals; Female; Follow-Up Studies; Graft Rejection - epidemiology; Graft Rejection - etiology; Graft Rejection - immunology; Heart Transplantation; Hepacivirus - immunology; hepatitis C; Hepatitis C Antigens - immunology; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - virology; Humans; Male; Middle Aged; Prospective Studies; rejection; Time Factors; Tissue Donors; viremia; heart transplantation; viremia; hepatitis C; direct-acting antivirals; rejection
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2020.06.022

Increased utilization of hepatitis C virus (HCV)-positive donors has increased transplantation rates. However, high levels of viremia have been documented in recipients of viremic donors. There is a knowledge gap in how transient viremia may impact acute cellular rejections (ACRs). In this study, 50 subjects received hearts from either viremic or non-viremic donors. The recipients of viremic donors were classified as nucleic acid amplification testing (NAT)+ group, and the remaining were classified as NAT-. All patients were monitored for viremia levels. Endomyocardial biopsies were performed through 180 days, evaluating the incidence of ACRs. A total of 50 HCV-naive recipients received hearts between 2018 and 2019. A total of 22 patients (44%) who received transplants from viremic donors developed viremia at a mean period of 7.2 ± 0.2 days. At that time, glecaprevir/pibrentasvir was initiated. In the viremia period (<56 days), 14 of 22 NAT+ recipients (64%) had ACR vs 5 of 28 NAT- group (18%) (p = 0.001). Through 180 days, 17 of 22 NAT+ recipients (77%) had a repeat rejection biopsy vs 12 of 28 NAT– recipients (43%) (p = 0.02). NAT+ biopsies demonstrated disparity of ACR distribution: negative, low-grade, and high-grade ACR in 84%, 12%, and 4%, respectively, vs 96%, 3%, and 1%, respectively, in the NAT– group (p = 0.03). The median time to first event was 26 (interquartile range [IQR]: 8–45) in the NAT+ group vs 65 (IQR: 44–84) days in the NAT–. Time to first event risk model revealed that NAT+ recipients had a significantly higher rate of ACR occurrences, adjusting for demographics (p = 0.004). Transient levels of viremia contributed to higher rates and severity of ACRs. Further investigation into the mechanisms of early immune activation in NAT+ recipients is required.