Donor/recipient match of IL28B to predict interferon response in recurrent hepatitis C

Background & Aims: The role of pre-treatment predictors of
Interferon (IFN) response has been overshadowed by the strong
predictive power of on-treatment viral kinetics. However, in
recurrent hepatitis C (HCV) following liver transplantation, a
strong negative pre-treatment predictor of IFN response would
have the benefit of further optimizing response-guided therapy
treatment algorithms while also positively impacting on patient
selection to reduce IFN related risks. Methods: Consecutive
patients with recurrent HCV treated with Ribavirin (Rbv) in combination
with PegIFN or IFN, were tested for the IL28B
rs12979860 SNP in DNA extracted from recipients blood sample
and paraffin-embedded donor liver graft. Results: Out of the
110 HCV patients transplanted from 2000 to 2010, 54 (49%)
received anti-HCV treatment and 48 completed post-treatment
follow-up (37 males, median age 54 years, median donor age
57 years, 65% Cyclosporine A, 85% HCV 1-4, median HCVRNA
3.5 x106 UI/ml, 29% S≥4 by Ishak, median interval to
treatment of 19 months, median treatment duration 45 weeks).
The remaining 56 patients were not treated due to non progressive
hepatitis (n=30), contraindications or severe co-morbidities
(n=26). Overall an SVR was achieved in 56% of
patients (49% genotype 1-4 vs. 100% genotype 2-3, p=0.01).
The CC IL28B genotype was less common in recipient blood
than in donor liver (24% vs 58%, p=0.001). In the 41 patients
with genotype1-4, the donor CC IL-28B genotype had more
SVR than CT/TT genotype (62% vs. 29%, p= 0.058), whereas
this was not true for recipient IL-28B genotype (70% vs. 42%,
p=0.15). Interestingly, when matching donor/recipient IL28B
genotype, patients with either donor or recipient CC genotype
had higher SVR rates than those without a CC (75% vs 20%,
p=0.009). By multivariate logistic regression analysis in genotype
1-4, the presence of an IL28B CC genotype either in the
donor or recipient (p=0.006; OR 11.7; 95% CI 2.05 - 66.55)
and Cyclosporine A (p=0.03; OR 5.83; 95% CI 1.13 - 30)
were independently associated with a SVR. Conclusion:
Although the combination of donor/recipient IL28B genotype
emerged as the strongest baseline predictor of treatment outcome
its added value to the existing therapeutic algorithm is
questionable in virtue of its unsatisfactory negative predictive
power.