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). There are differing reports concerning the effect of immunosuppression including the use of steroid, mycofenolate mofetil (MMF) and IL-2 antibody.

A group of researchers has been conducting a prospective randomized study comparing immune suppression protocols that include steroid-free regimens in patients with Hep C since 1999. In the first 50 patients randomized to Daclizumab + tacrolimus (FK) or Steroids + FK without preemptive antiviral strategy (Phase I), results have been mixed.

The group is currently conducting second phase with a modified protocol. 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). The study group received no steroids except for the treatment of biopsy proven rejection. Both arms received pre-emptive antiviral therapy with Pegasys and ribavirin.

Results

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 One patient in the study arm had suspected profound neurological toxicity from tacrolimus and was withdrawn from the study.

Incidence of rejection in the first 3 months were 0% in study arm and 40% in control arm. However, one 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%) who showed advanced fibrosis (Stage 3) 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).

Conclusions

The authors conclude, “OLT recipients with hepatitis C tolerated steroid free protocol. There is a trend in lowering steroids-related side effects in steroid-fee patients. However, its effect on hepatitis C recurrence cannot be determined until the completion of the study.”

Results of Protocol 1-year Biopsy

06/07/04

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. May 15-20, 2004. New Orleans, LA.