Elisabeth M G de Vries1, Martti Färkkilä2, Piotr Milkiewicz3, Johannes R Hov4,5,6,7, Bertus Eksteen8, Douglas Thorburn9, Olivier Chazouillères10, Albert Pares11, Ståle Nygård12,13,14, Odd H Gilja15,16, Ewa Wunsch17, Pietro Invernizzi18, Marco Carbone18, Francesca Bernuzzi18, Kirsten M Boberg4,5,7, Helge Røsjø14,19, William Rosenberg9, Ulrich H Beuers1, Cyriel Y Ponsioen1, Tom H Karlsen4,5,6,7, Mette Vesterhus4,15. 1. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. 2. Clinic of Gastroenterology, Helsinki University Hospital, Helsinki University, Helsinki, Finland. 3. Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland. 4. Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 5. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 6. K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway. 7. Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway. 8. Snyder Institute of Chronic Diseases, Department of Medicine, University of Calgary, Calgary, Canada. 9. UCL Institute for Liver and Digestive Health, Division of Medicine, University College London & Royal Free London, NHS Foundation Trust, London, UK. 10. Department of Hepatology, Hôpital Saint Antoine, Paris, France. 11. Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain. 12. Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital, Oslo, Norway. 13. Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway. 14. Center for Heart Failure Research, University of Oslo, Oslo, Norway. 15. National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway. 16. Department of Clinical Medicine, University of Bergen, Bergen, Norway. 17. Department of Translational Medicine, Pomeranian Medical University, Szczecin, Poland. 18. Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano (MI), Italy. 19. Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
Abstract
BACKGROUND & AIMS: Biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC) have not been firmly established. Enhanced liver fibrosis (ELF) test was previously reported to predict outcome in PSC. We aimed to validate the prognostic utility of ELF test in an independent, multi-centre, retrospective PSC study population. METHODS: We collected serum samples from PSC patients from seven countries. We estimated rates of transplant-free survival by the Kaplan-Meier method, used Cox proportional hazards regression to explore the association between ELF test and clinical outcome and determined prognostic performance of ELF test by computing the area under the receiver operating characteristic (AUC-ROC) curve. RESULTS: The final analysis included 534 PSC patients (61% males). Features of autoimmune hepatitis or concomitant inflammatory bowel disease affected 44 (8%) and 379 (71%) patients respectively. ELF test levels were higher in patients reaching the combined endpoint liver transplantation or death (median 10.9 [Interquartile range (IQR): 9.8-12.1]; n=24 deaths, 79 liver transplantations) compared to those censored (8.8 [IQR: 8.0-9.8]); P<.001. ELF test expressed as mild, moderate and severe fibrosis was significantly associated with the risk of reaching the endpoint (P<.001). ELF test independently predicted clinical outcome (Hazard ratio 1.31; 95% confidence interval [1.05-1.65]; P=.018), and enabled good discrimination between PSC patients with and without endpoint (AUC-ROC: 0.79). CONCLUSION: Our retrospective data validates the predictive utility of ELF test for clinical outcomes in PSC. The clinical utility of biomarkers for fibrosis in patients with PSC should be assessed in prospective patient cohorts.
BACKGROUND & AIMS: Biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC) have not been firmly established. Enhanced liver fibrosis (ELF) test was previously reported to predict outcome in PSC. We aimed to validate the prognostic utility of ELF test in an independent, multi-centre, retrospective PSC study population. METHODS: We collected serum samples from PSC patients from seven countries. We estimated rates of transplant-free survival by the Kaplan-Meier method, used Cox proportional hazards regression to explore the association between ELF test and clinical outcome and determined prognostic performance of ELF test by computing the area under the receiver operating characteristic (AUC-ROC) curve. RESULTS: The final analysis included 534 PSC patients (61% males). Features of autoimmune hepatitis or concomitant inflammatory bowel disease affected 44 (8%) and 379 (71%) patients respectively. ELF test levels were higher in patients reaching the combined endpoint liver transplantation or death (median 10.9 [Interquartile range (IQR): 9.8-12.1]; n=24 deaths, 79 liver transplantations) compared to those censored (8.8 [IQR: 8.0-9.8]); P<.001. ELF test expressed as mild, moderate and severe fibrosis was significantly associated with the risk of reaching the endpoint (P<.001). ELF test independently predicted clinical outcome (Hazard ratio 1.31; 95% confidence interval [1.05-1.65]; P=.018), and enabled good discrimination between PSC patients with and without endpoint (AUC-ROC: 0.79). CONCLUSION: Our retrospective data validates the predictive utility of ELF test for clinical outcomes in PSC. The clinical utility of biomarkers for fibrosis in patients with PSC should be assessed in prospective patient cohorts.
Authors: Nadine Nagy; Vivekananda G Sunkari; Gernot Kaber; Sonia Hasbun; Dung N Lam; Cate Speake; Srinath Sanda; Tracey L McLaughlin; Thomas N Wight; Steven R Long; Paul L Bollyky Journal: Matrix Biol Date: 2018-09-06 Impact factor: 11.583
Authors: Farhad Peerani; Lillian Du; Ellina Lytvyak; Vincent G Bain; Andrew L Mason; Robert J Bailey; Aldo J Montano-Loza Journal: Can Liver J Date: 2022-02-04
Authors: Michael Trauner; Yevgeniy Gindin; Zhaoshi Jiang; Chuhan Chung; G Mani Subramanian; Robert P Myers; Aliya Gulamhusein; Kris V Kowdley; Cynthia Levy; Zachary Goodman; Michael P Manns; Andrew J Muir; Christopher L Bowlus Journal: JHEP Rep Date: 2019-12-05
Authors: Paul M Trembling; Sophia Apostolidou; Aleksandra Gentry-Maharaj; Julie Parkes; Andy Ryan; Sudeep Tanwar; Matthew Burnell; Scott Harris; Usha Menon; William M Rosenberg Journal: BMC Gastroenterol Date: 2020-04-15 Impact factor: 3.067
Authors: Bertus Eksteen; Christopher L Bowlus; Aldo J Montano-Loza; Eric Lefebvre; Laurent Fischer; Pamela Vig; Eduardo Bruno Martins; Jawad Ahmad; Kidist K Yimam; Paul J Pockros; Jordan J Feld; Gerald Minuk; Cynthia Levy Journal: Hepatol Commun Date: 2020-12-22