| 1 | Recurrence and rejection in liver transplantation for primary sclerosing cholangitis显示文摘Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to f ibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can infl uence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible infl uence of rejection on the risk of recurrent disease in the allograft. | Bjarte Fosby Tom H Karlsen Espen Melum | 2012 | World Journal of Gastroenterology2012，18，1： | 8 |
| 5 | HLA variants related to primary sclerosing cholangitis influence rejection after liver transplantation显示文摘AIM:To investigate influence of human leukocyte antigen(HLA)and killer immunoglobuline-like receptor(KIR)genotypes on risks of acute rejection(AR)after liver transplantation(LTX).METHODS:In this retrospective study we included143 adult donor-recipient pairs with a minimum of 6mo follow-up after LTX for whom DNA was available from both donor and recipients.Clinical data,all early complications including episodes and severity of AR and graft/patient survival were registered.The diagnosis of AR was based on clinical,biochemical and histological criteria.All suspected episodes of AR were biopsy confirmed.Key classical HLA loci(HLA-A,HLA-B,HLA-C and HLA-DRB1)were genotyped using Sanger sequencing.16 KIR genes were genotyped using a novel real time PCR approach which allows for determination of the diploid copy number of each KIR gene.Immunohistochemical staining for T(CD3),B(CD20)and natural killer(NK)cells(CD56 and CD57)were performed on liver biopsies from 3 different patient groups[primary sclerosing cholangitis(PSC),primary biliary cirrhosis and non-autoimmune liver disease],10 in each group,with similar grade of AR.RESULTS:Fourty-four(31%)patients were transplanted on the basis of PSC,40%of them had AR vs 24%in the non-PSC group(P=0.04).No significant impact of donor-recipient matching for HLA and KIR genotypes was detected.In the overall recipient population an increased risk of AR was detected for HLA-B*08(P=0.002,OR=2.5;95%CI:1.4-4.6),HLA-C*07(P=0.001,OR=2.4;95%CI:1.4-4.0)and HLA-DRB1*03(P=0.03,OR=1.9;95%CI:1.0-3.3)and a decreased risk for HLA-DRB1*04(P=0.001,OR=0.2;95%CI:0.1-0.5).For HLA-B*08,HLA-C*07 and DRB1*04 the associations remained evident in a subgroup analysis of non-PSC recipients(P=0.04,P=0.003 and P=0.02,respectively).In PSC recipients corresponding P values were 0.002,0.17 and 0.01 for HLA-B*08,HLA-C*07and DRB1*04,respectively.A dosage effect of AR prevalence according to the PSC associated HLA alleles was also notable in the total recipient population.For HLA-B*08 the frequency of AR was 56%in HLA-B*08homozygous recipients,39%in heterozygous recipients and 21%in recipients lacking HLA-B*08(P=0.02).The same was observed for the HLA-C*07 allele with AR in 57%,27%and 18%in recipients being homozygous,heterozygous and lacking HLA-C*07 respectively(P=0.003).Immunohistochemical analysis showed similar infiltration of T,B and NK cells in biopsies with AR in all three groups.CONCLUSION:We found significant associations between the PSC-associated HLA-B*08,HLA-C*07,HLADRB1*03 and HLA-DRB1*04 alleles and risk of AR in liver transplant recipients. | Bjarte Fosby Sigrid Nss Johannes R Hov James Traherne Kirsten M Boberg John Trowsdale Aksel Foss Pl-Dag Line Andre Franke Espen Melum Helge Scott Tom H Karlsen | 2014 | World Journal of Gastroenterology2014，20，14： | 0 |
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