see related editorial on page x LIVER 1 © 2017 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY ORIGINAL CONTRIBUTIONS INTRODUCTION Primary biliary cholangitis (PBC), formerly known as pri- mary biliary cirrhosis (1), is a chronic cholestatic liver disease that may eventually result in severe illness, leading to death or liver transplantation (2,3). Despite the presumed autoimmune pathogenesis the efective therapies are those basically acting on improving cholestasis, mainly ursodeoxycholic acid (UDCA) (4), and more recently obeticholic acid (5). Te favorable efects with a probability of survival free of transplantation have been reported with UDCA, but still a signifcant proportion of patients deserve further treatments addressed to improve out- come (4). In the past two decades, fbrates, and particularly bezafbrate, commonly associated with UDCA, have demonstrated favorable efects in PBC, in terms of improving liver biochemistries with no or minor adverse efects (6–20). However, the studies lacked a sig- nifcant number of patients, had low doses of UDCA, or a very short period of treatment. Moreover, a controlled study including a small number of patients indicated that long-term bezafbrate treatment may result in renal insufciency (21). We have confrmed the encouraging efects of adding bezafbrate to UDCA for 1 year in 28 patients with PBC (20). Moreover, this report indicates that bezafbrate alleviated itching in 12 patients, an efect that resumed afer bezafbrate discontinuation. Four cases Effects of Bezafibrate on Outcome and Pruritus in Primary Biliary Cholangitis With Suboptimal Ursodeoxycholic Acid Response Anna Reig, MD 1 , Pilar Sesé, RN 1 and Albert Parés, MD, PhD 1 OBJECTIVES: Adding fibrates improves liver biochemistries in patients with primary biliary cholangitis (PBC) and suboptimal response to ursodeoxycholic acid (UDCA). As there are no consistent data regarding the course and outcome, we have assessed the effects of the combined treatment with UDCA and bezafibrate on a long-term basis. METHODS: A total of 48 patients (45 female) with PBC treated with UDCA and alkaline phosphatase (ALP) above 1.5 times upper normal levels (×UNL) were treated with bezafibrate (400 mg/day) plus UDCA (13–16 mg/kg/day). Changes in clinical features, liver biochemistries, and prognosis after therapy were assessed, as well as pruritus, using a visual analog scale (43 patients) and the 5-D descriptive pruritus scale. RESULTS: After a median of 38 months, 26 patients (54%) had normalized ALP. In these patients, jaundice, pruritus, and liver stiffness was lower, and age was higher than in patients who remained with elevated ALP. Biochemical improvement was less prominent in patients without ALP normalization. Five of these patients (23%) developed events of disease progression: 1 died, 3 were transplanted, and 1 developed hepatocellular carcinoma. Partial or complete itching relief was reported in all but one case with pruritus. Itching recurrence or worsening was observed after bezafibrate discontinuation. CONCLUSIONS: The long-term treatment with UDCA and bezafibrate results in excellent response, and is associated with a complete or partial itching relief. Incomplete ALP normalization was observed in patients with advanced disease who remained at risk for developing severe events. The combined treatment is mainly effective in patients with lower fibrosis and severity of cholestasis. Am J Gastroenterol advance online publication, 10 October 2017; doi:10.1038/ajg.2017.287 1 Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain. Correspondence: Albert Parés, MD, PhD, Liver Unit, Hospital Clínic, University of Barcelona, C/Villarroel 170, Barcelona 08036, Spain. E-mail: pares@ub.edu Received 16 May 2017; accepted 1 August 2017