Adult orthotopic liver transplantation in the United Kingdom and Ireland between 1994 and 2005

Background. The UK and Ireland Liver Transplant Audit collects information on all liver transplantations that are carried out in both countries. In this paper, we describe these transplantations and their outcomes in adult patients according to primary liver disease diagnosis, type of transplantation and period. Methods. A prospective cohort study of 7906 orthotopic liver transplantations carried out between April 1994 and June 2005 in the United Kingdom and Ireland. Multivariable logistic regression was used to investigate improvements in mortality according to period of transplantation adjusted for recipient and donor characteristics. Results. A total of 6,850 transplantations were done in adults (patients 16 years or older). Of these, 836 (12.2%) were first super-urgent procedures (33.7% men; median age 36 years), and 5,072 (74.0%) first elective procedures (60.0% men; median age 52 years). The percentage of patients who received a donor organ with abnormal appearance gradually increased, especially in patients receiving an elective transplant. Mortality at 90 days after first super-urgent transplant decreased from 29.6% (95% confidence interval: 23.5% to 36.9%) before October 1, 1996 to 16.0% (11.7% to 21.7%) after October 1, 2002. Considering the same time periods, mortality at 90 days after first elective transplant decreased from 10.6% (8.9% to 12.7%) to 7.7% (6.3% to 9.3%). Multivariable analysis demonstrated that these improvements cannot be explained by changes in the risk profile of recipients and donors. Conclusions. Patients undergoing a liver transplantation in the most recent years had a better survival than patients with similar characteristics transplanted 10 years earlier. Posttransplant survival has improved despite a deteriorating quality of donor organs

Sex and Age Are Determinants of the Clinical Phenotype of Primary Biliary Cirrhosis and Response to Ursodeoxycholic Acid

BACKGROUND, &amp; AIMS: Studies of primary biliary cirrhosis (PBC) phenotypes largely have been performed using small and selected populations. Study size has precluded investigation of important disease subgroups, such as men and young patients. We used a national patient cohort to obtain a better picture of PBC phenotypes.METHODS: We performed a cross-sectional study using the United Kingdom-PBC, patient cohort. Comprehensive data were collected for 2353 patients on diagnosis reports, response to therapy with ursodeoxycholic acid (UDCA), laboratory results, and symptom impact (assessed using the PBC-40 and other related measures).RESULTS: Seventy-nine percent of the patients reported current UDCA, therapy, with 80% meeting Paris response criteria. Men were significantly less likely to have responded to UDCA than women (72% vs 80% response rate; P &lt; .05); male sex was an independent predictor of nonresponse on multivariate analysis. Age at diagnosis was associated strongly and independently with response to UDCA; response rates ranged from 90% among patients who presented with PBC when they were older than age 70, to less than 50% for those younger than age 30 (P &lt; .0001). Patients who presented at younger ages also were significantly more likely not to respond to UDCA therapy, based on alanine aminotransferase and aspartate aminotransferase response criteria, and more likely to report fatigue and pruritus. Women had mean fatigue scores 32% higher than men's (P &lt; .0001). The increase in fatigue severity in women was related strongly (r = 0.58; P &lt; .0001) to higher levels of autonomic symptoms (P &lt; .0001).CONCLUSIONS: Among patients with PBC, response to UDCA, treatment and symptoms are related to sex and age at presentation, with the lowest response rates and highest levels of symptoms in women presenting at younger than age 50. Increased severity of fatigue in women is related to increased autonomic symptoms, making dysautonomia a plausible therapeutic target.</p

Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis

In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P &lt;5 × 10?8) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC