Immune-mediated graft dysfunction in liver transplant recipients with hepatitis C virus treated with direct-acting antiviral therapy.

Abstract

Interferon treatment of hepatitis C virus (HCV) infection after liver transplantation (LT) can result in immune-mediated graft dysfunction (IGD). The occurrence of, risk factors for, and outcomes of IGD with direct-acting antiviral (DAA) therapy have not been reported. We conducted a multicenter study of HCV+LT recipients who did or did not develop DAA-IGD (1 case: 2 controls-33 vs 66). Among all treated between 2014 and 2016, DAA-IGD occurred in 3.4% (33/978). IGD occurred only after treatment completion (76.0 [IQR, 47.0;176]). Among those treated, 48% had plasma cell hepatitis, 36% acute cellular rejection, 6% chronic rejection, and 9% combined findings. Median time to liver enzyme resolution was 77.5 days (IQR, 31.5;126). After diagnosis, hospitalizations, steroid-induced hyperglycemia, and infection occurred in a higher percentage of cases vs controls (33% vs 7.5%, 21% vs 1.5%, 9% vs 0%; all P < .05). Only one IGD patient died and none required retransplant. A multivariate regression analysis found that liver enzyme elevations during and soon after DAA therapy completion correlated with subsequent IGD. In conclusion, while DAA-IGD is uncommon, liver enzyme elevations during or after DAA therapy may be a sign of impending IGD. These indicators should guide clinicians to diagnose and treat IGD early before the more deleterious later clinical presentation.

• Authors: Christine Chan, Thomas Schiano, Eliana Agudelo, John Paul Haydek, Maarouf Hoteit, Marcela P Laurito, John P Norvell, Norah Terrault, Elizabeth C Verna, Amy Yang, Josh Levitsky
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 18 Issue 10 Pg. 2506-2512 (10 2018) ISSN: 1600-6143 [Electronic] United States
• PMID: 30075485 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Antiviral Agents

Topics

• Antiviral Agents (administration & dosage)
• Case-Control Studies
• Female
• Follow-Up Studies
• Graft Rejection (etiology)
• Graft Survival (immunology)
• Hepacivirus (drug effects)
• Hepatitis C (drug therapy, virology)
• Humans
• Liver Transplantation (adverse effects)
• Male
• Middle Aged
• Postoperative Complications
• Primary Graft Dysfunction (etiology)
• Prognosis
• Risk Factors