AN OPEN - LABEL PILOT STUDY OF AMANTADINE IN THE TREATMENT OF RECURRENT HEPATITIS C VIRUS (HCV) INFECTION FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION(OLT).

Abstract

736 Recurrent HCV infection is a major cause of allograft dysfunction following OLT. Treatment of recurrent HCV with currently available medications such as alpha interferon is effective. Preliminary data suggest that amantadine may have anti - viral activity against HCV. Aim: To assess the efficacy of amantadine in the treatment of recurrent HCV infection following OLT.Methods: Seven consecutive patients with recurrent hepatitis C following OLT were studied. All patients had histological evidence of recurrent hepatitis and detectable HCV RNA. The patients were treated with amantadine using an oral dose of 100 mg twice daily for 12 weeks. Pre and post treatment biochemical parameters and viral levels were obtained. No alterations in immunosuppression were made as part of the study.Results: The mean time to diagnosis of recurrent hepatitis C was 3.3 months following OLT (range 1 - 6 months). One patient had a normal pre treatment ALT level. Prior to the institution of therapy, the median RNA level was 2.8 million copies / ml. The median RNA level following treatment was 7.1 million copies/ ml. No patient experienced clearance of viral RNA during treatment. Of the patients treated, 4 had a reduction in the level of detectable viral RNA; 3 patients were noted to have increases in the level of viral RNA. Of the patients who experienced a reduction in the level of HCV viral RNA, the mean reduction was 3.9 million copies / ml (range 440,000 - 5.7 million copies / ml). Of the patients who had increased levels of HCV during treatment, the mean increase in viral level was 4.8 million copies / ml (range 4.3 - 8.2 million copies / ml). No significant improvements were seen in the mean pre and post treatment ALT (128 vs. 131 U/L respectively), AST (124 vs. 118 U/L), total bilirubin (1.3 vs. 1.2 mg/dL), or alkaline phosphatase (152 vs. 150 U/L). There was no correlation between the reduction or increase in viral RNA and a reduction or increase in ALT level. One patient developed rapidly progressive liver failure and died while receiving therapy. Two patients (29%) reported an improvement or stabilization in symptoms of fatigue. Side effects were common, with 4 patients (57%) experiencing orthostatic symptoms and / or increased symptoms of fatigue. Two patients required discontinuation of the drug (at 1 and 4 weeks of therapy, respectively), one because of orthostatic symptoms and one because of the development of a rash. Conclusions: In patients with recurrent hepatitis C following OLT, amantadine therapy did not clear viral RNA. Moreover, no consistent virological response pattern was seen with amantadine therapy; some patients had a reduction in the level of HCV RNA, however a similar number of patients had an increase in viral RNA with treatment. No significant improvement in biochemical parameters or symptoms of fatigue was observed. Side effects of amantadine therapy were frequent. Amantadine does not appear to have a role as monotherapy in the treatment of recurrent hepatitis C following OLT.