Long‐term immune response after liver transplantation in patients with spontaneous or post‐treatment HCV‐RNA clearance

Recurrent HCV infection after liver transplantation is universal and sustained clearance of HCV‐RNA rarely occurs. The aim of this study was to characterize cell‐mediated immunity and cytokine production in HCV‐infected patients after liver transplant. The study included 6 pretransplantation patients (PT) and 15 liver transplanted patients, including 5 with spontaneous HCV‐RNA clearance (SC group), 5 with sustained virological response after antiviral treatment (SVR group), and 5 no response (NR group). The control group included 5 HCV‐RNA negative, anti‐HCV negative healthy individuals. This study examines proliferative T‐cell response and cytokine production (gamma‐interferon and IL‐10) after HCV specific and phytohemagglutinin (PHA) stimulation in cultured peripheral blood mononuclear cells (PBMCs) from each group. Multispecific proliferative responses to HCV antigens (mean Stimulation Index; SI) were higher in the SVR group (mean SI 7.4 ± 2) and SC group, as compared with the NR group ( P < .05, vs SVR) and PT group ( P < .05, vs SVR and SC). After PHA stimulation, gamma‐interferon levels were similar to controls (4330 ± 640 pg/ml) in the SC (4474 ± 300 pg/mL) and SVR groups (3647 ± 300 pg/mL), but were significantly lower than controls in the PT (401 ± 331 pg/mL; P < .02) and NR groups (546 ± 360 pg/mL; P < .01). IL‐10 production after PHA stimulation was similar in SC, SVR, and controls (647 ± 279 pg/mL, 674 ± 310 pg/mL and 841 ± 294 pg/mL, respectively), but was lower in PT patients (232 ± 94 pg/mL). The NR group showed high basal IL‐10 production with little increase after stimulation. In conclusion, liver post‐transplantation patients with spontaneous clearance of HCV‐RNA and those with sustained viral response after therapy showed an immune response despite immunosuppression that might have contributed to their favorable outcome. (Liver Transpl 2004;10:584–594.)