The rate of SVR was strongly associated with the IL28B genotype of both the recipient and donor liver. The rate of SVR according
to recipient IL28B genotype was 58% versus 47% versus 0% for CC versus CT versus TT, respectively, odds ratio (OR) = 3.43; 95% CI, 1.42-8.3; P = 0.0062 (Fig. 1A). The rate of SVR according to donor genotype was 59% versus 30% versus 0% for CC versus CT versus TT, respectively; OR = 4.00; 95% CI = 1.46-10.98; P = 0.0071 (Fig. 1B). Notably, no patient with either recipient or donor TT genotype attained SVR (n = 14). SVR was independently associated with both recipient and donor IL28B genotype in a regression model that included both as predictors (P = 0.0026 and P = 0.0030, respectively). We then considered treatment outcome according to combined
recipient:donor IL28B genotype Rapamycin cell line pairing (CC versus non-CC genotype, given the primary results and data from the nontransplant literature that shows that the major benefit of the IL28B polymorphism occurs in CC homozygotes).9, 10 SVR was lowest in non-CC recipients of a non-CC donor liver, increased if either the recipient or the donor was CC at the IL28B polymorphism and was maximal in the setting of CC recipients of a CC liver (SVR rates 3/19 [16%] versus 11/22 [50%]/5/12 [42%] versus 6/7 [86%], P = 0.0095; Fig. 1C). No other clinical/biochemical variable Copanlisib was associated with virological clearance in this cohort. Recipient IL28B CC genotype was associated with significantly less fibrosis formation in the early posttransplant period than recipients with non-CC genotypes. A total of 172 patients underwent a biopsy
at year 1. Twenty-six had genotype TT, 48 had genotype CC, 80 had the heterogeneous CT genotype, and the IL28B genotype could not be determined in 18. At 1 year after transplantation, when biopsy data were most complete, 9/28 (32%) patients with recipient IL28B TT genotype had fibrosis stage 2 or higher, compared to 6/52 (12%) patients with genotype CC and 20/80 (25%) patients with the heterogeneous CT genotype (Pearson chi-square P = 0.024 for heptaminol the comparison CC versus TT). Donor IL28B genotype was not significantly associated with fibrosis at 1 year. Allograft inflammation at 1 year, measured by histologic activity index, did not vary significantly with donor or recipient genotype (Mann-Whitney TT versus CC P = 0.430). Histologic activity index was higher, but not significantly so, at the time of recurrence of HCV in recipients with a recipient IL28B genotype: CC, 5.0 (range, 3.0-7.0); CT, 4.0 (range, 3.0-6.0); and TT, 3.0 (range, 2.5-4.0), Kruskal-Wallis (overall) P = 0.165. ALT levels were lower for recipient IL28B genotype CC than for TT at 3-6 months post-OLT (138 U/L for TT, 93 U/L for CT, and 60 U/L for CC; Mann-Whitney P = 0.030 for CC versus TT).