PLASMATIC MEASUREMENT OF RIBAVIRIN LEVELS DURING TREATMENT OF RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION WITH PEGINTERFERON ALFA-2B AND RIBAVIRIN COMBINATION:

O373 Aims: After liver transplantation (LT) for HCV-related cirrhosis, recurrence of HCV infection is universal and the risk of progression to cirrhosis is high. The modalities and efficacy of antiviral therapy in this indication are still controversial. We recently reported that combination therapy by pegylated-interferon alfa2b and ribavirin may be well tolerated and beneficial in this field. Sustained virological response was obtained in 9/20 patients. Deceptive results obtained in all previously published studies of treatment with alfa-interferon and ribavirin were related to its poor tolerance. We present herein the results of plasmatic measurement of ribavirin levels in transplanted patients when using increasing dosage of ribavirin (from 400 to 1000-1200 mg/day), in comparison to a control cohort of non transplant patients. Patients and Methods : Seventeen control patients (9 women and et 8 men, median age 51, 5 years (range 33-73)) were compared to twelve liver transplant patients (2 women and 10 men, median age 55 years (range 44-65)). In 76% of patients, HCV infection was genotype 1. All patients were treated by a combination of ribavirin and pegylated-interferon alfa2b for more than 1 month. A total of 54 blood samples were taken (1.8 per patient) for ribavirin trough levels. Results: Virological response was obtained in 8/17 patients in the control group and in 6/12 in LT patients. Ribavirin dose was lower in the LT group (8,785 vs 12,975 mg/kg/day) but trough plasmatic levels were the same in both group (2,568 vs 2,477 mg/l) This was probably related to impaired renal function in the LT group (serum creatinine: 112,6 vs 73,5 microm/l). No discontinuation of ribavirin therapy was observed in both groups. Hemoglobin level was the same in both groups (109,5 g/l in LT patients vs 119,5 g/l in control group). Conclusion: These results demonstrate the feasibility of ribavirin monitoring and suggest the interest of plasmatic measurement of ribavirin trough levels during therapy. Ribavirin dosage can also be adapted according to hematological tolerance and kidney function without compromising its efficacy.