THE PROBLEM OF VIRAL HEPATITIS IN LIVER TRANSPLANTATION

G. Klintmalm¹, C.G. Fasola², G. Netto³, L. Jennings⁴, H..C..V..-.3. Study group^4
1, Baylor University Medical Center, Dallas/TX/UNITED STATES OF AMERICA, ²Transplantation Services, Scott and White Healthcare, Temple/UNITED STATES OF AMERICA, ³, Johns Hopkins, Baltimore/MD/UNITED STATES OF AMERICA, ⁴Transplantation Surgery, Baylor University Medical Center, Dallas/TX/UNITED STATES OF AMERICA

Body: The HCV-3 study was designed to assess the efficacy and safety of an steroid (Pred)-freeimmunosuppression (IS) regimen using daclizumab (DAC), tacrolimus (TAC) and mycophenolate mofetil (MMF) to minimize the rates of acute rejection, HCV recurrence (R) and adverse events (AE) post OLT.This was an open label, prospective, multicenter study (n=18) on 312 adults HCV-OLT recipients randomized (1:1:2) to 3 IS arms: Arm 1 (n=80): TAC + Pred; Arm 2 (n=79): TAC + Pred + MMF; Arm 3(n=153): DAC (3 doses, on days (d) 1, 3 and 8) + TAC + MMF. This study is now completed. The most relevant findings are presented, respectively, for arms 1, 2 and 3:
1.- No differences found regarding safety data (AE: new onset of diabetes, HTN, dyslipidemia, infections or malignancy).
2.- Similar overall 2-year patient (83.1%, 80.9% and 86.7%, p= NS) and graft survivals (78.6%,78.4% and 84.2%, p= NS).
3.- No differences in acute rejection rates. Day 90: 14%, 6% and 9%; day 730: 14%, 13% and 14%.
4.- Biochemical hepatitis (ALT or AST > 100 IU or, T. Bilirubin > 1.5 mg/dl) was less in arm 3 (45%, 37% and 27%, p=0.022) at day 90, but no different afterwards.
5.- At year 2, severe HCVR (stage > 3 fibrosis) rate was lesser in arm 3: 34%, 27% and 20%, p=0.04.
6.- Accelerate HCVR (recipients with stage > 3, at year 1, censored) analysis focused on the 2nd year fibrosis progression and, it affected more arm 1 (34%) than arm 3 (16%, p= 0.002); moresteroids-treated (Rx) patients (arms 1 + 2: 29%) than no-steroid Rx (arm 3: 16%, p= 0.01) and, more no-MMF Rx (arm 1: 34%) than MMF Rx (arms 2 + 3: 19%, p= 0.004)
7.- Significant inflammation (grade >2), at year 1, was associated with more severe HCV recurrence (stage > 3) at year 2 in arm 1 (39%) vs 2 (24%) or 3 (11%), p= 0.002, becomingan early marker for severe fibrosis.
8.- Risk factors found for severe HCV recurrence (stage > 3) included: a) Donor age > 50-64 years(y), hazard ratio (HR): 1.8 (p= 0.02) and donor age > 65 y., HR: 3.0(p=0.002); b) cold ischemia time > 7 hours, HR: 1.88, (p< 0.001) and, c) arm 1 (compared to arm 3) HR: 4.6, (p< 0.001).
CONCLUSIONS: A limitation of this study is the short-term follow up (2 years). However, this study suggests that HCV-OLT recipients exposed to IS based on an steroid-free regimen, MMF, tacrolimus andIL-2R antibody induction - as in arm 3 - can have a superior outcome compared to other IS regimens.

Disclosure: All authors have declared no conflicts of interest.