TY - JOUR T1 - Prevention of endpoints in primary biliary cholangitis with ursodeoxycholic acid: quantifying the benefit JF - Gut JO - Gut SP - 1377 LP - 1378 DO - 10.1136/gutjnl-2019-320355 VL - 69 IS - 8 AU - Jörn M Schattenberg Y1 - 2020/08/01 UR - http://gut.bmj.com/content/69/8/1377.abstract N2 - Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with an established benefit for patients suffering from primary biliary cholangitis (PBC). It was first introduced in the 60s and took until the late 90s to demonstrate a survival benefit in large meta-cohort studies.1 Since then, UDCA is the established first-line therapy according to current guidelines.2 The benefit of UDCA is multidimensional, and patients receiving UDCA experience increased transplant-free survival, a decreased risk of hepatocellular carcinoma and potentially improved quality of life.3–5 The survival benefit is predicted by a number biochemical markers that reflect cholestasis and that are accepted surrogates of the treatment response—a fact that has accelerated drug development and approval. Interestingly, even patients who are considered incomplete responders to UDCA—characterised by persistently elevated alkaline phosphates levels (ALPs) or abnormal bilirubin—a survival benefit compared with patients that are not on UDCA can be detected.4 The mechanism by which UDCA mediates these effects are numerous and involve: (1) protection of chonlangiocytes from cytotoxic hydrophobic bile acids, (2) increased hepatobiliary secretion of bile components and (3) protection of hepatocytes from bile acid-induced apoptosis. UDCA enrichment in the bile is linear to the administered dose and thus a sufficient dose—typically ranging between 13 mg/kg and 15 mg/kg bodyweight—is required to achieve therapeutic efficacy. The safety profile of UDCA is positive with only few patients experiencing dyspepsia, lose stools or mild diarrhoea. Therefore, all patients diagnosed with PBC according to current criteria should be started on UDCA as primary treatment immediately.More recently, second-line therapies—including bezafibrate and the steroidal FXR-agonist obeticholic acid (OCA)—have been trialled in … ER -