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Abstract Details
Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one-year non-responders and predicts survival
Liver Int. 2023 May 8. doi: 10.1111/liv.15592. Online ahead of print.
1Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
2Schiff Center for Liver Diseases, Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida, USA.
3University of Toronto, Toronto, Ontario, Canada.
4National Institute for Health Research Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK.
5Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, Paris, France.
6Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
7Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
8Arizona State University, Phoenix, Arizona, USA.
9Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
10Liver Institute Northwest, Washington, USA.
11Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
12Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
13IRCCS Negrar, Verona, Italy.
14Divison of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada.
15Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
16Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, Italy.
17Division of Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, Department of Biomedical Sciences, Humanitas University, Rozzano (Milan), Italy.
18Digestive and Liver diseases, UT Southwestern Medical Center, Dallas, Texas, USA.
19Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, Full Member of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece.
20The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, UK.
21Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
22Liver Unit, Hospital Clínic de Barcelona, Health Care Provider of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER) CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
23Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract
Background and aims: Patients with primary biliary cholangitis (PBC) and insufficient response to ursodeoxycholic acid (UDCA), currently assessed after 1 year, are candidates for second-line therapy. The aims of this study are to assess biochemical response pattern and determine the utility of alkaline phosphatase (ALP) at six months as a predictor of insufficient response.
Methods: UDCA-treated patients in the GLOBAL PBC database with available liver biochemistries at one year were included. POISE criteria were used to assess response to treatment, defined as ALP <1.67 × upper limit of normal (ULN) and normal total bilirubin at one year. Various thresholds of ALP at six months were evaluated to predict insufficient response based on negative predictive value (NPV) and that with nearest to 90% NPV was selected.
Results: For the study, 1362 patients were included, 1232 (90.5%) female, mean age of 54 years. The POISE criteria were met by 56.4% (n = 768) of patients at one year. The median ALP (IQR) of those who met POISE criteria compared to those who did not was 1.05 × ULN (0.82-1.33) vs. 2.37 × ULN (1.72-3.69) at six months (p < .001). Of 235 patients with serum ALP >1.9 × ULN at six months, 89% did not achieve POISE criteria (NPV) after one year of UDCA. Of those with insufficient response by POISE criteria at one year, 210 (67%) had an ALP >1.9 × ULN at six months and thus would have been identified early.
Conclusions: We can identify patients for second-line therapy at six months using an ALP threshold of 1.9 × ULN, given that approximately 90% of these patients are non-responders according to POISE criteria.