Journal
LIVER INTERNATIONAL
Volume 31, Issue 8, Pages 1102-1109Publisher
WILEY
DOI: 10.1111/j.1478-3231.2010.02422.x
Keywords
CC chemokine receptor 5-delta32; CCR5-Delta 32; liver transplantation; NAS; nonanastomotic biliary strictures; primary sclerosing cholangitis; PSC
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Background: The role of the immune system in the pathogenesis of nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) is unclear. A loss-of-function mutation in the CC chemokine receptor 5 (CCR5-Delta 32) leads to changes in the immune system, including impaired chemotaxis of regulatory T cells. Aim: To investigate the impact of the CCR5-Delta 32 mutation on the development of NAS. Methods: In 384 OLTs, we assessed the CCR5 genotype in donors and recipients and correlated this with the occurrence of NAS. Results: The CCR5-Delta 32 allele was found in 65 (16.9%) recipients. The cumulative incidence of NAS at 5 years was 6.5% in wild-type (Wt) recipients vs 17.2% for carriers of the CCR5-Delta 32 allele (P < 0.01). In recipients with CCR5-Delta 32, 50% of all NAS occurred >2 years after OLT, compared with 10% in the Wt group. In multivariate regression analysis, the adjusted risk of developing NAS was four-fold higher in recipients with CCR5-Delta 32 (P < 0.01). The highest risk of NAS was seen in patients transplanted for primary sclerosing cholangitis (PSC), who also carried CCR5-Delta 32 (relative risk 5.4, 95% confidence interval 2.2-12.9; P < 0.01). Donor CCR5 genotype had no impact on the occurrence of NAS. Conclusions: Patients with the CCR5-Delta 32 mutation have a four-fold higher risk of developing NAS, compared with Wt recipients. This risk is even higher in patients with CCR5-Delta 32 transplanted for PSC. Late development of NAS is significantly more present in patients with CCR5-Delta 32. These data suggest that the immune system plays a critical role in the development of NAS after OLT.
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