Steroid-Free Immunosuppression for Liver Transplantation Recipients with Hepatitis C

Recurrence of Hepatitis C (Hep C) has been a difficult dilemma in liver transplantation (OLT). Effect of immunosuppresion including the use of steroid, mycofenolate mofetil (MMF), and IL-2 antibody has been reported in a quite large discrepancy.

Researchers have been performing prospective randomized study comparing immunusuppression protocols that includes steroid-free regimen in patients with Hep C since 1999. T first 50 patients were randomized to Daclizumab+tacrolimus (FK) or Steroids +FK without preemptive antiviral strategy (Phase I). Results were mixed.

The investigators are currently conducting second phase with a modified protocol. Reported here are their early results from the Phase II study.

OLT recipients with Hep C were randomized to 2 treatment arms: Daclizumab+FK+MMF (study arm) and Steroids+FK+MMF (control arm). Study group received no steroids except for the treatment of biopsy proven rejection.

Both arms received pre-emptive anti-viral therapy with Pegasys (peginterferon alfa-2a) and ribavirin.

Results 

Twenty-six patients have been enrolled (10 in study arm and 16 in control). All patients are alive. One patient in the study arm had suspected profound neurological toxicity from tacrolimus and was withdrawn from the study.

Incidences of rejection in the first 3 months were 0% in study arm and 40% in control arm. However, a patient in the study arm developed severe rejection after 6 months requiring OKT 3. This patient was crossed over to the steroid (control) arm.

Only 7 had reached protocol 1-year biopsy. There were 2 patients in the control arm (33%) showed advanced fibrosis (Stage3) but 3 (50%) are stage 0-1. Only one in the study arm reached 1-year showing stage 2 fibrosis.

Comparing the common side effects of steroids (study vs control): hypertension (33% vs 63%), PTDM (11% vs 44%), and wound infection (22% vs 31%) (all of them, p=NS).

The authors conclude, “OLT recipients with Hep C tolerated steroid free protocol. There is a trend in lowering steroids related side effects in steroid-fee patients. However, its effect on Hep C recurrence has yet to be determined at the completion of the study.”

05/21/04

Reference
T Kato and others. Steroid-Free Immunosuppression for Liver Transplantation Recipients with Hepatitis C - A Prospective Randomized Study. Abstract 1174 (poster).  Digestive Disease Week 2004. May 15-20, 2004. New Orleans, LA.