IL-2 receptor antagonist [basiliximab] is associated with rapid fibrosis progression in patients with recurrent hepatitis c after liver transplantation using serial biopsy specimens

ABSTRACT

Recurrence of hepatitis C virus [HCV] infection following orthotopic liver transplantation [OLT] is universal. There is paucity of data on the safety and efficacy of interleukin [IL]-2 receptor antagonist [IL-2RA] when added to the standard immunosuppression regimen in OLT recipients with recurrent HCV infection. To evaluate the efficacy of IL-2RA [Basiliximab] in preventing acute cellular rejection [ACR] in patients with recurrent HCV infection after OLT and to assess the impact of IL-2RA in promoting fibrosis progression in post-OLT recurrent HCV infection. Using an electronic pathology database, we identified all OLT/HCV patients with at least 2 post-OLT liver biopsies [1998-2006]. Standard immunosuppression consisted of steroids and calcineurin inhibitor with and without mycophenolate mofetil. All patients who were transplanted after May 2004 received IL- 2RA induction therapy. The Ludwig-Batts system was used to stage all biopsies [593 biopsies from 124 patients]. The first biopsy that showed post-OLT fibrosis or the last follow-up biopsy was used for time- to-progression analysis. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify factors associated with the progression of fibrosis. ACR was significantly [p<0.001] lower in patients who received IL-2RA [20 of 70, 29%] compared to those who did not [33 of 54, 61%]. The median [25%ile, 75%ile] follow-up was 12.1 [6.1, 23.9] months during which 61% of patients had progression of fibrosis. Univariate analysis revealed that a higher HCV RNA load at 4 months post-OLT [p=0.002], cytomegalovirus [CMV] infection [p<0.001], use of steroid therapy for ACR [p=0.043], and use of IL-2RA [p<0.001] were associated with higher hazards for the pro- gression of fibrosis. Viral load at 4 months post-OLT was significantly [p=0.025] higher in patients who had IL-2RA therapy [median [25%ile, 75%ile] 2.9 [1.0, 5.0] _10[6] vs. 1.4 [1.0, 2.3] _10[6]]. In multivariate analysis, patients who received IL-2RA therapy were 3.1 [95% CI 1.8-5.3] times more likely to develop fi- brosis than those who did not treated with IL-2RA. Steroid therapy for ACR remained significantly [Hazard Ratio=2.9, p=0.002] associated with the progression of fibrosis. IL-2RA [Basiliximab] decreases the rate of ACR. However, it may be associated with more rapid histological progression of the disease in post-OLT recurrent HCV