Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

The serum concentrations of CA19-9 and carcinoembryonic antigen (CEA) were measured in 150 consecutive patients with histologically proven liver disease admitted to a liver unit for transplant assessment. A significant proportion of the cases studied had a CA19-9 above the upper limit of the reference range (35 kU/L): alcoholic liver disease (73%), primary sclerosing cholangitis (61%), primary biliary cirrhosis (60%), chronic hepatitis B (71%), chronic hepatitis C (84%), autoimmune hepatitis (36%) and hepatocellular carcinoma (54%). CEA was only elevated in a small proportion of the patients with benign liver disease and the degree of elevation was small (15-37 micrograms/L). Significantly raised CEA was observed in two patients (15%) with hepatocellular carcinoma. Statistically significant correlations were observed between the serum CA19-9 concentration and standard parameters of liver dysfunction: positive correlations with aspartate aminotransferase, alkaline phosphatase and bilirubin and negative correlations with albumin and gamma-glutamyltransferase. Positive relationships were also observed between CA19-9 and both CEA and creatinine. Both increased production of CA19-9 from biliary epithelial cells and decreased clearance due to cholestasis may be contributing to the elevation of CA19-9 in the bloodstream. Our data indicate that caution is needed in the interpretation of CA19-9 results in the presence of liver dysfunction.

This study investigated the presence of mRNA coding for interferon gamma

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The isolation of gliadin specific HLA-DQ2