Effectiveness and Safety of Everolimus in the Treatment of Autoimmune Hepatitis Related to Anti-Hepatitis C Virus Therapy After Liver Transplant: Three Case Reports

Treatment of recurrent hepatitis C after liver transplantation is indicated in selected cases. During the combined treatment with pegylated interferon and ribavirin, some patients develop immune-mediated liver dysfunction similar to the previously described de novo autoimmune hepatitis. Herein we have presented three liver transplant patients who during or after combined antiviral treatment were diagnosed as autoimmune hepatitis related to interferon based on their clinical, biochemical, and liver histology features. There were two women and one man, of ages 49, 52, and 49 years who were transplanted due to cirrhosis related to hepatitis C virus genotype 1. In two patients, elevated liver enzymes occurred during antiviral therapy and in the third, after the therapy. The diagnosis of autoimmune hepatitis was reached after excluding other possible causes. One patient had a sustained viral response; and two cases were nonresponders. Antinuclear antibodies were present in two subjects and antinuclear antibodies and anti-smooth muscle antibodies in the other case. First-line treatment of autoimmune hepatitis with prednisone and azathioprine stabilized clinical and biochemical parameters'. In order to avoid the long-term use of prednisone, everolimus was introduced in the three patients. Interestingly, hepatitis C did not progress and clinical, biochemical, as well as histological parameters stabilized. In one patient, the liver fibrosis stage as assessed by histology showed improvement. However, one subject experienced repeated cerebral hemorrhage and died. Although this is heterogeneous population with partially known characteristics, with a difficult differential diagnosis, the objectives of preserving liver function and avoiding recurrent progressive hepatitis C seemed to be achieved by adding everolimus. In addition, we totally stopped prednisone therapy. In conclusion, treatment with everolimus in combination with cyclosporine achieved a partial remission in two liver transplan cases of autoimmune hepatitis related to interferon therapy.