The combination of primary sclerosing cholangitis and CCR5-Δ32 in recipients is strongly associated with the development of nonanastomotic biliary strictures after liver transplantation.

Abstract

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-Δ32) leads to changes in the immune system, including impaired chemotaxis of regulatory T cells.

AIM:

To investigate the impact of the CCR5-Δ32 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-Δ32 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-Δ32 allele (P<0.01). In recipients with CCR5-Δ32, 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-Δ32 (P<0.01). The highest risk of NAS was seen in patients transplanted for primary sclerosing cholangitis (PSC), who also carried CCR5-Δ32 (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-Δ32 mutation have a four-fold higher risk of developing NAS, compared with Wt recipients. This risk is even higher in patients with CCR5-Δ32 transplanted for PSC. Late development of NAS is significantly more present in patients with CCR5-Δ32. These data suggest that the immune system plays a critical role in the development of NAS after OLT.

• Authors: Sanna op den Dries, Carlijn I Buis, Jelle Adelmeijer, Eric J Van der Jagt, Elizabeth B Haagsma, Ton Lisman, Robert J Porte
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 31 Issue 8 Pg. 1102-9 (Sep 2011) ISSN: 1478-3231 [Electronic] United States
• PMID: 21134114 (Publication Type: Journal Article)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

• Receptors, CCR5

Topics

• Adult
• Chi-Square Distribution
• Cholangitis, Sclerosing (complications, mortality, surgery)
• Cholestasis (etiology, genetics, immunology, mortality)
• Constriction, Pathologic
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Graft Survival
• Humans
• Immunity, Innate (genetics)
• Kaplan-Meier Estimate
• Liver Transplantation (adverse effects, mortality)
• Logistic Models
• Male
• Middle Aged
• Mutation
• Netherlands
• Receptors, CCR5 (genetics)
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Survival Rate
• Time Factors