Background:

HCV recurrence is virtually universal in viremic patients at the time of transplant. Long term patient and graft survival is inferior in HCV patients unless sustained virologic response (SVR) is achieved. The introduction of protease inhibitor based therapy has shown promising early results in the treatment of recurrent HCV in transplant recipients.

Aim:

To determine tolerability and treatment response of telaprevir (TPV) based therapy in liver transplant recipients with recurrent HCV (rHCV) disease.

Methods:

Subjects with biopsy proven rHCV (Fibrosis Stage + Hepatitis Grade ≥ 3) were considered. 14 patients initiated tx with TPV + PEG-IFN/Ribavirin (P/R) for 12 weeks, with continuation of P/R for an additional 12 weeks or longer based on virologic response. Immunosuppression (IS) during TPV therapy was dose reduced (tacrolimus 0.5mg q7-10d; everolimus 0.25mg q 3-5d; prednisone 5mg daily) to adjust for CYP3A inhibition by TPV. Patients were monitored for response to therapy, side effects, renal function, and CNI toxicity.

Results:

14 patients initiated therapy with TPV+P/R. 13 failed prior P/R tx alone. 3 pts required early discontinuation of therapy (1 – side effects; 1 – CNI toxicity; 1 – critically ill, achieved RVR). 2 pts failed therapy after a period of dosing noncompliance due to po intolerance unrelated to treatment.

The remaining 9 pts tolerated the duration of therapy without major side effects. Renal function remained stable in 10/11 pts, and worsened from CRI stage 3 to 4 in 1 pt. 2 pts required transfusion for anemia. 33% (3/9) achieved SVR and remain off all therapy. 33% (3/9) discontinued tx due to futility rules (1, week 4; 2, week 12) after showing early partial response. The remaining 33% (3/9) demonstrated eVR, though ultimately relapsed within 10 wks of cessation of P/R therapy. 1 pt developed de novo AIH, and 1 pt had mild acute rejection (both bx proven), both easily treated with addition of mmf and minor increase in CNI dose.

Conclusions:

TPV based therapy can be safely administered and well tolerated with manageable side effects in transplant recipients. Rejection and CNI toxicity did not prove to be problematic. 66% of patients completing TPV tx achieved eVR. Of these, 50% achieved SVR and 50% relapsed after cessation of P/R. Further studies are needed to determine duration of therapy and the effects of IS on rHCV response.

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