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.

No abstract

The acid perfusion test (APT) is a test of esophageal acid sensitivity. In gastroesophageal reflux disease (GERD), the APT has largely been superseded by indexes derived from 24-hr esophageal pH monitoring: symptom index (SI), symptom sensitivity index (SSI), and symptom association probability (SAP). To evaluate the role of APT in patients with GERD we compared values of SI, SSI, and SAP in 126 APT+ and 146 APT- patients. Median values for SI, SSI, and SAP were higher in the APT+ compared with the APT- group (P < 0.001). More patients had a positive SI, SSI, and SAP in the APT+ compared with the APT- group (SI, P < 0.0001; SSI and SAP, P < 0.001). Patients with a negative APT were unlikely to have symptoms caused by acid reflux (negative predictive value, 86%). APT may be useful in detecting acid sensitivity in patients who do not report symptoms on 24-hr esophageal pH monitoring.

No abstract

No abstract