27 research outputs found
Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis
We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P \u3c 1 × 10−4) identified in a previous genome-wide association study. Combined analysis of the genome-wide association and replication datasets identified IRF5-TNPO3 (combined P = 8.66 × 10−13), 7q12-21 (combined P = 3.50 × 10−13) and MMEL1 (combined P = 3.15 × 10−8) as new primary biliary cirrhosis susceptibility loci. Fine-mapping studies showed that a single variant accounts for the IRF5-TNPO3 association. As these loci are implicated in other autoimmune conditions, these findings confirm genetic overlap among such diseases
Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.
Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC
The specificity of fatigue in primary biliary cirrhosis:evaluation of a large clinic practice
Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis
IgG4 related disease - a retrospective descriptive study highlighting Canadian experiences in diagnosis and management
BACKGROUND: Appreciating the utility of published diagnostic criteria for autoimmune pancreatitis, when compared to the characteristics of patients clinically managed as having disease, informs and refines ongoing clinical practice. METHODS: Comparative retrospective descriptive evaluation of patients with autoimmune pancreatitis including dedicated radiology review. RESULTS: 66 subjects with radiographic OR clinical features of autoimmune pancreatitis were initially identifiable (Male: n = 50), with 55 confirmed for evaluation. The most common presentation included pain (67%), weight loss (65%), and jaundice (62%). Diffuse enlargement of the pancreas was evident in 38%, whilst multifocal, focal, or atrophic changes were seen in 7%, 33% and 9% respectively. 13% had no pancreatic parenchymal involvement. Peripheral rim enhancement was seen in 23 patients (42%). Where discernible, disease was a) Sclerosing pancreatitis and cholangitis, n = 21; b) Sclerosing cholangitis, n = 9; c) Sclerosing pancreatitis, n = 4; d) Sclerosing pancreatitis and cholangitis with pancreatic pseudotumour, n = 7; e) Sclerosing cholangitis with hepatic pseudotumour, n = 3; f) Sclerosing pancreatitis with pancreatic pseudotumour, n = 1. 56% of the patients had systemic manifestations and the median serum IgG4 at diagnosis was 5.12 g/L. The Korean criteria identified most patients (82%) compared to HISORt (55%) or the Japan Pancreas Society (56%). The majority (HISORt 60%; Japan Pancreas Society 55%; Korean 58%) met diagnostic criterion by radiological findings and elevated serum IgG4. Treatment and response did not differ when stratified by diagnostic criteria. CONCLUSION: Our descriptive and retrospective dataset confirms that in non-expert practice settings, autoimmune pancreatitis scoring systems with a focus on radiology and serology capture most patients who are clinically felt to have disease
A validated clinical tool for the prediction of varices in PBC: The Newcastle Varices in PBC Score
Background & Aims - Gastro-oesophageal varices (GOV) can occur in early stage primary biliary cirrhosis (PBC), making it difficult to identify the appropriate time to begin screening with oesophageo-gastro-duodenoscopy (OGD). Our aim was to develop and validate a clinical tool to predict the probability of finding GOV in PBC patients.
Methods - A cross-sectional retrospective study analysing clinical data of 330 PBC patients who underwent an OGD at the Freeman Hospital, Newcastle was used to create a predictive tool, the Newcastle Varices in PBC (NVP) Score, that was externally validated in PBC patients from Cambridge (UK) and Toronto (Canada).
Results - 48% of the Newcastle, 31% of the Cambridge, and 22% of the Toronto cohorts of PBC patients had GOV. Twenty-five percent (95% CI 18–32%) of the Newcastle cohort had GOV diagnosed at an index variceal bleed. Of the others, 37% (95% CI 28–46%) bled after a median of 1.5 years (IQR 3.75). Transplant-free survival was significantly better in those without GOV than in those with GOV (p <0.001), but similar in patients with GOV that bled and those that did not (p = 0.1). The NVP score (%Probability) = 1/[1 + exp^−(9.186 + 0.001 * alkaline phosphatase in IU − 0.178 * albumin in g/L − 0.015 * platelet × 109) was validated in 2 external cohorts and was highly discriminant (AUROC 0.86). Cost consequences analyses revealed the NVP score to be as accurate as, but more economical than using either OGD directly or other risk scores for screening PBC patients.
Conclusions - The NVP score is an inexpensive, non-invasive, externally validated tool that accurately predicts GOV in PBC
MOESM3 of The human, F-actin-based cytoskeleton as a mutagen sensor
Additional file 3. BLCA2 mut counts
Optimising risk stratification in primary biliary cirrhosis:AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response
Background & Aims: Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). Such stratification inadequately captures cirrhosis/portal hypertension, recognised factors associated with adverse events. Methods: We evaluated a cohort of PBC patients (n = 386) attending the Liver Unit in Birmingham (derivation cohort), seeking to identify risk-variables associated with transplant-free survival independent of UDCA-response. A validation cohort was provided through well-characterised patients attending the Toronto Center for Liver Diseases (n = 479) and Jena University Hospital (n = 150). Results: On multivariate analysis, factors at diagnosis associated with liver transplant (LT)/death were patient age (HR:1.06; p 0.54 at baseline was predictive of LT/death (adjusted HR: 2.40; p 0.54 vs. biochemical-responders with a lower APRI-r1 (p <0.01 and p <0.001, respectively); non-responders with high APRI-r1 had the poorest outcomes (p <0.001 and p <0.001). Conclusion: In PBC, elevated APRI is associated with future risk of adverse events, independently and additively of UDCA-response. This cross-centre, robustly validated observation will contribute to ongoing efforts to refine existing risk-stratification tools, as well as direct focus for new therapies in patients with PBC. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved