Ischemic Type Biliary Lesions nach orthotoper Lebertransplantation - ein immunologisches Problem?

Abstract

Ischemic type biliary lesions (ITBL) are a major complication following orthotopic liver transplantation (OLT). In many cases re-OLT is indicated. Multiple factors have been claimed to be reasonable for ITBL; here we present a new immunological risk factor: CC-Chemokines play a key role in the recruitment of leukocytes during ischemia-reperfusion damage and acute rejection. Therefore the CC-chemokine-receptor 5 (CCR5) and its functionless CCR5-delta-32-polymorphism (CCR5Δ32) might have an influence on the grafts pathology after OLT. In 146 patients after OLT the CCR5 was analyzed with regard to the CCR5Δ32 by PCR. 120 patients (82,1%) showed a normal receptor (wildtype) whereas 26 patients suffered from the CCR5 Δ32 (17,9%) (25 hétérozygote, 1 homozygote). ITBL occurred in 14 patients out of 120 with normal CCR5 and in 8 cases out of 26 patients with CCR5Δ32 (p = 0,01). The univariate analysis of donor and recipient conditions (CCR5 wildtype vs. CCR5Δ32) showed no differences in donor gamma GT (48 vs. 39 U/1, p = 0,615), donor age (45 vs. 50 years, p = 0,210), cold ischemia time (529 vs. 566 min, p = 0,382), and warm ischemia time (36 vs. 39 min, p = 0,333). Acute rejection occurred in 34% in the wildtype group and in 31% in the CCR5Δ32 group (p = 1,000). The CMV-infection rate was 25% in the wildtype group and in 37,5% in the CCR5Δ32 group (p = 0,356). The multivariate analysis showed a significant influence on the development of ITBL by CCR5Δ32 (p = 0,003, OR 9,35). The hereditary CCR5Δ32 has a significant influence on the development of ITBL and should therefore be screened before OLT. This can be subclassified new as immunogen-etic-biliary-lesions. Ongoing investigations must show if an increased immunosuppression could be beneficial in patients suffering from CCR5Δ32-polymorphism.