Hepatitis C virus viral kinetics during α-2a or α-2b pegylated interferon plus ribavirin therapy in liver transplant recipients with different immunosuppression regimes

Abstract 

Background

Predictors of sustained virological response (SVR) to antiviral therapy post-liver transplantation (LT) for chronic hepatitis C are needed. In non-transplanted patients, viral kinetics can predict SVR.

Objectives

To determine the early viral kinetics in LT recipients with different immunosuppression (tacrolimus – Tac- vs. cyclosporine – CsA-) during treatment with peg-IFN+RBV.

Study design

Prospective pilot study in HCV-1b infected patients: (LT CsA n=8; Tac n=8; non-LT n=4), treated with IFN α-2a vs. α-2b (180μg or 1.5μg/kg, respectively) once weekly plus weight-based RBV. Median CsA or Tac baseline trough levels were 141 and 7.70ng/mL, respectively. HCV-RNA was quantified before treatment and after 3, 6, 12h; days 1–6; and weeks 4, 12, 24, 48 and 78 (follow-up).

Results

Different kinetics were observed: early viral load declines with shoulder phase (n=12), delayed monophasic without first phase (n=5, all CsA), and biphasic (n=1) or flat (n=1), without influence of IL28B rs12979860 donor/recipient alleles. In LT, median declines (log₁₀UI/mL) at week 4 were −3.62 and −1.49 for Tac vs. CsA; and −2.10 vs.−1.50 for IFN α-2a vs. α-2b (NS), with a trend for faster declines in Tac patients. Generalized additive models suggested a cut-off for predicting response in LT patients of 30 days for Tac, but beyond day 40 for CsA.

Conclusion

In LT, the viral kinetics during peg-IFN+RBV treatment is delayed. HCV-RNA at 48h. may not be predictive of response, and CsA-immunosupressed patients with delayed monophasic declines may potentially achieve ETVR and SVR despite unfavourable or absent early viral load declines.

Abbreviations: PCR, polymerase chain reaction, ALT, alanine aminotransferase, AST, aspartate aminotransferase, GGT, gamma-glutamyl-aminotransferase, HCV-RNA, Hepatitis C virus ribonucleic acid

Keywords: HCV, Antiviral therapy, OLT, Cyclosporine, Tacrolimus