Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation.
OBJECTIVE
To determine whether increased immunosuppression is a contributor to poor outcome in hepatitis C-infected orthotopic liver transplant (OLT) recipients, we retrospectively analyzed the consequences of using OKT3 in our program for steroid-resistant rejection (SRR).


METHODS
We compared the histological recurrence of HCV in two contemporary cohorts of OLT recipients. Group 1 consisted of HCV-positive patients who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of age-, gender-, and initial immunosuppression-matched HCV-positive controls who were treated with at least one steroid pulse for acute cellular rejection but who did not require treatment with OKT3. Liver biopsies were obtained per protocol within the first month and as necessary to evaluate abnormalities in serum liver chemistries.


RESULTS
Mean and median follow-up were comparable for the two groups. Recurrence of HCV was diagnosed by histological verification and was documented in 16 of 19 (84.2%) group 1 patients versus 17 of 33 (51.5%) group 2 patients (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 the first year post-OLT (p = 0.0004). The histological severity score, based on the most recent liver biopsy at long-term follow-up or the explant biopsy if the patient required retransplantation, was significantly higher in group 1. Moreover, cirrhosis was demonstrable in a greater proportion of allografts in patients who had received OKT3 at some point (26.3% vs. 6%, p = 0.028). Long-term follow-up revealed a trend toward higher alanine aminotransferase levels (p = 0.05) and total bilirubin (p = 0.08) in group 1 patients.


CONCLUSIONS
Our data suggest that allograft hepatitis in patients with preexisting HCV occurs earlier and with greater severity in patients treated with OKT3 for SRR, compared with age-, gender-, and initial immunosuppression-matched contemporary controls. Treatment of SRR with OKT3 may jeopardize long-term allograft function and survival in HCV-infected recipients by enhancing viral hepatitis recurrence. Clearly, the recognition of recurrent HCV and differentiation from acute cellular rejection remains a crucial issue in managing the OLT recipient with HCV.
Rosen
H R
HR
Department of Medicine, UCLA School of Medicine and The Dumont-UCLA Transplant Center, Los Angeles, California 90095, USA.
Shackleton
C R
CR
Higa
L
L
Gralnek
I M
IM
Farmer
D A
DA
McDiarmid
S V
SV
Holt
C
C
Lewin
K J
KJ
Busuttil
R W
RW
Martin
P
P
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D015331:Cohort Studies; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy / Q000628:therapy; D006085:Graft Survival; D006526:Hepatitis C / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008099:Liver / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D016031:Liver Transplantation / Q000473:pathology; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000009:adverse effects*; D012008:Recurrence; D012086:Reoperation; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D000410:Alanine Transaminase; D001663:Bilirubin; D008775:Methylprednisolone