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

Use of chromoendoscopy versus white light endoscopy for colorectal cancer surveillance in inflammatory bowel disease patients with primary sclerosing cholangitis cohort: A six year experience

Patients with inflammatory bowel disease (IBD) are at increased risk for development of dysplasia and colorectal cancer (CRC), with a further 6-fold increased risk in those with primary sclerosing cholangitis (PSC) versus their non-PSC-IBD counterparts. Preneoplastic tissue in IBD patients is often flat and multifocal and may not be appreciated in up to one-third of colonoscopies. The dysplasia yield from surveillance colonoscopy can be improved by spraying dyes that highlight subtle changes in the architecture of the colonic mucosa. Limited data exists on outcomes of chromoendoscopy in PSC-IBD population

Transferrin Metabolism in Alcoholic Liver-Disease

The metabolism of transferrin was studied using purified 125I\u2010labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 \ub1 0.3 gm per liter vs. 2.9 \ub1 0.2; p < 0.01), resulting from diminished total body synthesis (0.9 \ub1 0.2 mg per kg per hr vs. 1.8 \ub1 0.2; p < 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 \ub1 0.3 mg per kg per hr) was significantly increased when compared with controls (p < 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p < 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerate

Use of chromoendoscopy versus white light endoscopy for colorectal cancer surveillance in inflammatory bowel disease patients with primary sclerosing cholangitis cohort: A six year experience

Patients with inflammatory bowel disease (IBD) are at increased risk for development of dysplasia and colorectal cancer (CRC), with a further 6-fold increased risk in those with primary sclerosing cholangitis (PSC) versus their non-PSC-IBD counterparts. Preneoplastic tissue in IBD patients is often flat and multifocal and may not be appreciated in up to one-third of colonoscopies. The dysplasia yield from surveillance colonoscopy can be improved by spraying dyes that highlight subtle changes in the architecture of the colonic mucosa. Limited data exists on outcomes of chromoendoscopy in PSC-IBD population

Ulcerative colitis and persistent liver dysfunction

Six hundred and eighty-one patients with ulcerative colitis who attend the outpatient clinic in Oxford have been screened for the presence of persistently abnormal liver function tests. Of the 21 patients (3.0 per cent) found with abnormal liver function 17 (2.4 per cent) were shown by cholangiography to have primary sclerosing cholangitis. The liver biopsies from those patients demonstrated a wide range of histological features and were diagnostic of primary sclerosing cholangitis in only 50 per cent of the patients. When persistently abnormal liver function tests are demonstrated in patients with ulcerative colitis it is likely that primary sclerosing cholangitis will be present (81 per cent of patients in this study), and in order to make a reliable diagnosis it is necessary to perform cholangiography in addition to liver biopsy. A close association with primary sclerosing cholangitis and histocomptability antigens HLA B8 and DR3 is also reported