USE OF OKT3 IS ASSOCIATED WITH EARLY AND SEVERE RECURRENCE OF HEPATITIS-C AFTER LIVER-TRANSPLANTATION

Objective: To determine whether increased immuno-suppression is a cont ributor to poor outcome in hepatitis C-infected orthotopic liver trans plant (OLT) recipients, we retrospectively analyzed the consequences o f using OKT3 in our program for steroid-resistant rejection (SRR). Met hods: We compared the histological recurrence of HCV in two contempora ry cohorts of OLT recipients. Group 1 consisted of HCV-positive patien ts who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of a ge-, gender-, and initial immunosuppression-matched HCV-positive contr ols who were treated with at least one steroid pulse for acute cellula r rejection but who did not require treatment with OKT3. Liver biopsie s were obtained per protocol within the first month and as necessary t o evaluate abnormalities in serum liver chemistries. Results: Mean and median follow-up were comparable for the two groups. Recurrence of HC V was diagnosed by histological verification and was documented in 16 of 19 (84.2%) group I patients versus 17 of 33 (51.5%) group 2 patient s (p = 0.03). The interval to recurrence was significantly shorter in patients who received OKT3 (p = 0.028). Logistic regression identified OKT3 as a significant risk factor for the recurrence of HCV within th e first year post-OLT (p = 0.0004). The histological severity score, b ased on the most recent liver biopsy at long-term follow-up or the exp lant biopsy if the patient required retransplantation, was significant ly higher in group 1. Moreover, cirrhosis was demonstrable in a greate r proportion of allografts in patients who had received OKT3 at some p oint (26.3% vs. 6%,p = 0.028). Long-term follow-up revealed a trend to ward higher alanine aminotransferase levels (p = 0.05) and total bilir ubin (p = 0.08) in group 1 patients. Conclusions: Our data suggest tha t allograft hepatitis in patients with preexisting HCV occurs earlier and with greater severity in patients treated with OKT3 for SRR, compa red with age-, gender-, and initial immunosuppression-matched contempo rary controls. Treatment of SRR with OKT3 may jeopardize long-term all ograft function and survival in HCV-infected recipients by enhancing v iral hepatitis recurrence. Clearly, the recognition of recurrent HCV a nd differentiation from acute cellular rejection remains a crucial iss ue in managing the OLT recipient with HCV.