Recipient levels and function of von Willebrand factor prior to liver transplantation and its consumption in the course of grafting correlate with hepatocellular damage and outcome

Von Willebrand factor (vWF) is a major platelet adhesion molecule at sites of vascular injury, such as observed in ischemia/reperfusion injury following orthotopic liver transplantation (OLT). Thirty-three OLT patients were divided into groups with elevated or low markers of hepatocellular damage (high and low-HD). Whole-blood aggregometry was performed to evaluate platelet function. Multimeric analysis was utilized to evaluate functional vWF levels in the course of OLT. Donor and recipient demographics were comparable among groups. Low-HD patients demonstrated better preserved coagulation parameters on POD 1-6 if contrasted to high-HD patients. One year graft survival for the high-HD group was lower than low-HD patients (P = 0.037). Preoperative vWF-dependent platelet aggregation and functional vWF plasma levels correlated directly with alanine transaminase levels early after OLT as did the decrease of functional vWF to reperfusion. In summary, these data suggest that vWF may serve as a significant mediator of platelet recruitment and hepatocellular injury in the graft following reperfusion

Loci from a genome-wide analysis of bilirubin levels are associated with gallstone risk and composition

BACKGROUND & AIMS: Genome-wide association studies have mapped loci that are associated with serum levels of bilirubin. Bilirubin is a major component of gallstones so we investigated whether these variants predict gallstone bilirubin content and overall risk for gallstones. METHODS: Loci that were identified in a meta-analysis to attain a genome-wide significance level of a P value less than 1.0 107 (UGT1A1, SLCO1B1, LST-3TM12, SLCO1A2) were analyzed in 1018 individuals with known gallstone composition. Gallstone risk was analyzed in 2606 German choleystecomized individuals and 1121 controls and was replicated in 210 cases and 496 controls from South America. RESULTS: By using the presence of bilirubin as a phenotype, variants rs6742078 (UGT1A1; P .003), rs4149056 (SLCO1B1; P .003), and rs4149000 (SLCO1A2; P .015) were associated with gallstone composition. In regression analyses, only UGT1A1 and SLCO1B1 were independently retained in the model. UGT1A1 (rs6742078; P .018) was associated with overall gallstone risk. In a sex-stratified analysis, only male carriers of rs6742078 had an increased risk for gallstone disease (P 2.1 107; odds ratiorecessive, 2.34; Pwomen .47). The sex-specific association of rs6742078 was confirmed in samples from South America (Pmen .046; odds ratiorecessive, 2.19; Pwomen .96). CONCLUSIONS: The UGT1A1 Gilbert syndrome variant rs6742078 is associated with gallstone disease in men; further studies are required regarding the sex-specific physiology of bilirubin and bile acid metabolism. Variants of ABCG8 and UGT1A1 are the 2 major risk factors for overall gallstone disease, they contribute a population attributable risk of 21.2% among men.Fil: Buch, Stephan. University Hospital Schleswig-Holstein; AlemaniaFil: Schafmayer, Clemens. University Hospital Schleswig-Holstein; AlemaniaFil: Völzke, Henry. University of Greifswald; AlemaniaFil: Seeger, Marcus. University Hospital Schleswig-Holstein; AlemaniaFil: Miquel, Juan F.. Pontificia Universidad Católica de Chile; ChileFil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Egberts, Jan H.. University Hospital Schleswig-Holstein; AlemaniaFil: Arlt, Alexander. University Hospital Schleswig-Holstein; AlemaniaFil: Pirola, Carlos Jose. University Hospital Schleswig-Holstein; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lerch, Markus M.. University of Greifswald; AlemaniaFil: John, Ulrich. University of Greifswald; AlemaniaFil: Franke, Andre. University Hospital Schleswig-Holstein; AlemaniaFil: von Kampen, Oliver. University Hospital Schleswig-Holstein; AlemaniaFil: Brosch, Mario. University Hospital Schleswig-Holstein; AlemaniaFil: Nothnagel, Michael. University Hospital Schleswig-Holstein; AlemaniaFil: Kratzer, Wolfgang. Universitat Ulm; AlemaniaFil: Boehm, Bernhard O.. Universitat Ulm; AlemaniaFil: Bröring, Dieter C.. University Hospital Schleswig-Holstein; AlemaniaFil: Schreiber, Stefan. University Hospital Schleswig-Holstein; AlemaniaFil: Krawczak, Michael. University Hospital Schleswig-Holstein; AlemaniaFil: Hampe, Jochen. University Hospital Schleswig-Holstein; Alemani