Improved Liver Function and Decreased Hepatitis C Viral Load After Tacrolimus Was Replaced by Cyclosporine R. Lorho, B. Turlin, A.S. de Lajarte-Thirouard, C. Camus, M. Lakehal, P. Compagnon, B. Meunier, K. Boudjema, and M. Messner ABSTRACT Potential antiviral properties of cyclosporine against hepatitis C virus have been high- lighted in several publications. Therefore, we investigated the effect of a switch from tacrolimus to cyclosporine in a liver transplant recipient with recurrent hepatitis C who did not respond to antiviral therapy. The patient received a liver transplant for hepatitis C cirrhosis. Initial immunosuppressive treatment was based on tacrolimus. Because of viral activity, a combined therapy was initiated 20 months later including interferon and ribavirine. Then, due to a lack of virological and biochemical response, tacrolimus was replaced by cyclosporine (Neoral), while maintaining the same antiviral therapy. Decreases in the viral load and transaminases levels were observed. T HE POSSIBILITY THAT cyclosporine may be active against hepatitis C virus (HCV) in vitro, especially when combined with alpha-interferon, 1 has been raised in a number of articles. Cyclosporine suppresses both viral replication and expression of its proteins. 2 Its mechanism of action appears to be independent of that of interferon, but there may be some synergy between them. 3 Since no such effect has been observed with tacrolimus, cyclosporine may be a more suitable immunosuppressive agent to treat HCV following liver transplantation. We therefore attempted to replace tacrolimus with cyclosporine in a patient with HCV who was failing to respond to antiviral treatment. CASE REPORT The patient presented signs of chronic non-A, non-B hepatitis in 1987. The investigations suggested that he had probably been infected in 1971 at which time he was 17 years old. During a road traffic accident his left kidney had been damaged; he required transfusions before a nephrectomy to stop the bleeding. He was later shown to carry the HCV genotype 1b. No treatment was instigated. In June 2001, the patient presented with signs of severe liver failure (Child-Pugh C) combined with portal hypertension. He was placed on the waiting list and was given a donor liver on September 11, 2001. After the operation, his condition improved rapidly on the following regimen: tacrolimus (residual concentra- tion 5 to 10 ng/mL); mycophenolate mofetil (MMF) (3 g/d then 1 g/d until withdrawal in March 2003); and prednisone (20 mg/d, gradually stepped down to 5 mg/d). An examination on April 2002 showed an initially satisfactory outcome with transaminase activities just slightly above normal (SGOT = 28 IU/L, SGPT = 55 IU/L) and low viral load (60  10 3 IU/mL). However, in July of the following year (2003), there were clear signs of viral reactivation: SGOT = 480 IU/L and SGPT = 647 IU/L, Metavir histological score was A2F2, and viral load was 3323  10 3 IU/mL. Bitherapy was instigated with peginterferon 2a combined with ribavirin. After an initial decrease in the transaminases in January (SGOT 165 IU/L and SGPT 178 IU/L), 3 months later the cytolytic activity was increased (SGOT = 219 IU/L and SGPT = 175 IU/L) and the viral load remained high (126  10 3 IU/mL). It was concluded that the virus was not responding to the antiviral drugs. Given the lack of response, it was decided to replace the tacrolimus by cyclosporine (Neoral) without changing the antiviral bitherapy (April 2004). The patient’s condition then improved markedly (Fig. 1) with a significant reduction in viral load (45  10 3 IU/mL on July 5, 2004), and decreased transaminase activities (SGOT = 96 IU/L and SGPT = 106 IU/L on September 3, 2004). The switch did not result in either increased blood pressure or impaired kidney function. DISCUSSION In this liver transplant patient on tacrolimus, the viral response to treatment for recurrent HCV was poor. The From the Department of Liver Disease (R.L., M.M.), Depart- ment of Pathology and Cytology (A.S.D.L.-T., B.T.), Department of Infectious Diseases and Intensive Care (C.C.), and Depart- ment of Internal Surgery (M.L., P.C., B.M., K.B.), CHU Pontchail- lou, Rennes, France. Address reprint requests to Dr Richard Lorho, Service des Maladies du Foie, Hôpital Pontchaillou, 2 rue Henri le Guilloux, 35033 Rennes cedex 9, France. E-mail: richard.lorho@ chu-rennes.fr © 2005 by Elsevier Inc. All rights reserved. 0041-1345/05/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2005.05.019 Transplantation Proceedings, 37, 2871–2872 (2005) 2871