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


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


METHODS
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 (180 μg or 1.5 μg/kg, respectively) once weekly plus weight-based RBV. Median CsA or Tac baseline trough levels were 141 and 7.70 ng/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 (log(10)UI/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.


CONCLUSIONS
In LT, the viral kinetics during peg-IFN+RBV treatment is delayed. HCV-RNA at 48 h. 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.
Hepatology-Liver Transplantation Unit, Digestive Medicine Service, Hospital Universitari La Fe, Spain.
Marina
M
Berenguer
Cecilia
C
Ortíz-Cantó
Juan José
JJ
Abellán
Victoria
V
Aguilera
Angel
A
Rubín
Martín
M
Prieto
F Xavier
FX
López-Labrador
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D016867:Immunocompromised Host; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007700:Kinetics; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a