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

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

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22 Scopus citations


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.

Original languageEnglish
Pages (from-to)2506-2512
Number of pages7
JournalAmerican Journal of Transplantation
Issue number10
StatePublished - Oct 2018


  • antibiotic: antiviral
  • clinical research/practice
  • immunosuppression/ immune modulation
  • infection and infectious agents—viral: hepatitis C
  • infectious disease
  • liver allograft function/dysfunction
  • liver disease: infectious
  • liver transplantation/hepatology
  • rejection


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