Daily low-dose Tacrolimus (TAC) is a save and efficient immunosuppressive regimen during triple drug therapy post liver transplant
Aims: Graft loss from hepatitis C virus (HCV) recurrence remains a major problem after liver transplantation (LT), and the response to standard therapy is poor. Triple therapy opens a new perspective for better graft and patient survival but severe drug interactions are a potential limitation in LT patients. We report our experience using low-dose tacrolimus (TAC) on a daily base in patients who undergo HCV triple therapy due to post LT recurrence of HCV infection.
Methods: 16 patients with HCV genotype (GT) 1 recurrence after liver transplant were treated with telaprevir (TVR), pegylated interferon-alpha (PEG) and ribavirin (RBV) for 12 weeks followed by 12 or 36 weeks of dual therapy. After initiating TVR, TAC dosage was skipped until start of decline of therapeutic level and then administered as 0,1 mg with once or twice daily dosing. Levels of TAC as well as other lab values were monitored closely. Once TVR was stopped the TAC was reinstituted with a goal to achieve pre-TVR doses gradually. Safety and efficacy data were gathered for time of treatment.
Results: All of the 13 male and 3 female patients completed the 12 weeks of triple therapy. At week 4, 15 of the patients were found to be HCV-RNA < 12 IU/mL (RealTime-HCV-Assay). Moreover, the target was not detected below the quantification limit of the test. All patients are still under treatment at present and no viral break through has been experienced so far. Therapeutic TAC levels were closely monitored and kept stable all throughout the triple phase. No drug toxicity and no episodes of rejection were seen during the TVR period of therapy. 70% of the patients exhibited hematological side effects requiring RBV dose reduction, the administration of erythropoietin or blood transfusions. All patients tolerated the medications, no one stopped early.
Conclusion: We report a large single center experience for treating HCV GT1 recurrence after LT with TVR based triple therapy. Our data provide evidence that drug-drug interactions between TVR and Tacrolimus can be handeled appropriately through close monitoring of trough levels. Adequate dosage adjustment is possible, avoiding toxicity or rejection in these patients, together with a high early viral response (EVR).