1. Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis
- Author
-
Laura Rubbia-Brandt, Karim Abdelrahman, Astrid Marot, Gene Y. Im, Gianluca Bontempi, Yujin Hoshida, Denis Franchimont, Thierry Gustot, Christine Sempoux, Eric Trepo, Delphine Degré, Won-Min Song, Jacques Devière, Nicolas Goossens, Joan Saldarriaga, Swan N. Thung, Charlotte Minsart, Christophe Moreno, Jean Henrion, Antonio Colaprico, Pierre Deltenre, Valerio Lucidi, Pieter Demetter, Venugopalan D. Nair, Laurent Spahr, Naoto Fujiwara, Thomas Sersté, Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology [Brussels, Belgium], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Experimental Gastroenterology [Brussels, Belgium], Université libre de Bruxelles (ULB), Department of Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Division of Gastroenterology and Hepatology [Geneva, Switzerland], Geneva University Hospital (HUG), Department of Genetics and Genomic Sciences, Interuniversity Institute of Bioinformatics in Brussels (IB2), Université libre de Bruxelles (ULB)-Vrije Universiteit Brussel (VUB), Machine Learning Group [Brussels, Belgium] (Department d'Informatique), Division of Gastroenterology and Hepatology [Lausanne, Switzerland], Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Department of Pathology [Brussels, Belgium], Université libre de Bruxelles (ULB)-Hôpital Erasmes, Department of Clinical Pathology [Lausanne, Switzerland], Lausanne University Hospital-Institute of Pathology [Lausanne, Switzerland], Recanati/Miller Transplantation Institute [New York, NY, USA], Unité d'Hématologie [CH de Jolimont-Lobbes, Belgium], Centre Hospitalier de Jolimont-Lobbes [Haine Saint-Paul, Belgium], Department of Abdominal Surgery [Brussels, Belgium], Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Centre de Chirurgie Hépato-Biliaire de l'ULB [Brussels, Belgium], Department of Pathology and Immunology [Geneva, Switzerland] (Clinical Pathology Division), Université de Genève = University of Geneva (UNIGE)-Geneva University Hospitals - HUG [Switzerland], Department of Neurology [New York, NY, USA], Service d'Hépato-Gastroentérologie [Haine-Saint-Paul, Belgium], Hôpital de Jolimont [Haine-Saint-Paul, Belgium], The study was supported by the Fonds Erasme (Edouard and Suzanne Jacobs Convention), the Belgian Association for the Study of the Liver, and a Research Project (T100914F) from the Fund for Scientific Research-FNRS (F.R.S.-FNRS). Eric Trépo is a Research Associate of the F.R.S.-FNRS and Denis Franchimont is a Research Director of the F.R.S.-FNRS. Nicolas Goossens received funding from the FLAGS and Nuovo-Soldati foundations. Yujin Hoshida is supported by NIH/NIDDK DK099558, European Union ERC-2014-AdG-671231HEPCIR, Irma T. Hirschl Trust, and US Department of Defense (W81XWH-16-1-0363). Antonio Colaprico and Gianluca Bontempi are supported by the BridgeIRIS project funded by INNOVIRIS, Brussels-Capital Region, Brussels, Belgium., European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Lausanne University Hospital [Switzerland]-Institute of Pathology [Lausanne, Switzerland], University of Geneva [Switzerland]-Geneva University Hospitals - HUG [Switzerland], daulny, anne, and Cell circuits as targets and biomarkers for liver disease and cancer prevention - HEPCIR - - H20202016-01-01 - 2020-12-31 - 671231 - VALID
- Subjects
0301 basic medicine ,Male ,Alcoholic liver disease ,Cirrhosis ,Time Factors ,medicine.medical_treatment ,Biopsy ,Kaplan-Meier Estimate ,Liver transplantation ,ddc:616.07 ,Gastroenterology ,Severity of Illness Index ,Liver disease ,0302 clinical medicine ,Model for End-Stage Liver Disease ,Belgium ,Adrenal Cortex Hormones ,Risk Factors ,Oligonucleotide Array Sequence Analysis ,ddc:616 ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,medicine.diagnostic_test ,musculoskeletal, neural, and ocular physiology ,Middle Aged ,3. Good health ,Phenotype ,Treatment Outcome ,Liver biopsy ,Area Under Curve ,030211 gastroenterology & hepatology ,Female ,Transcription ,Adult ,Genetic Markers ,medicine.medical_specialty ,Alcoholic hepatitis ,macromolecular substances ,Risk Assessment ,Article ,Decision Support Techniques ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Proportional Hazards Models ,Hepatitis ,Hepatology ,Ethanol ,business.industry ,Hepatitis, Alcoholic ,Gene Expression Profiling ,Reproducibility of Results ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,medicine.disease ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Surgery ,MELD ,030104 developmental biology ,ROC Curve ,nervous system ,business ,Transcriptome ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; BACKGROUND & AIMS:Patients with severe alcoholic hepatitis (AH) have a high risk of death within 90 days. Corticosteroids, which can cause severe adverse events, are the only treatment that increases short-term survival. It is a challenge to predict outcomes of patients with severe AH. Therefore, we developed a scoring system to predict patient survival, integrating baseline molecular and clinical variables.METHODS:We obtained fixed liver biopsy samples from 71 consecutive patients diagnosed with severe AH and treated with corticosteroids from July 2006 through December 2013 in Brussels, Belgium (derivation cohort). Gene expression patterns were analyzed by microarrays and clinical data were collected for 180 days. We identified gene expression signatures and clinical data that are associated with survival without liver transplantation at 90 and 180 days after initiation of corticosteroid therapy. Findings were validated using liver biopsies from 48 consecutive patients with severe AH treated with corticosteroids, collected from March 2010 through February 2015 at hospitals in Belgium and Switzerland (validation cohort 1) and in liver biopsies from 20 patients (9 received corticosteroid treatment), collected from January 2012 through May 2015 in the United States (validation cohort 2).RESULTS:We integrated data on expression patterns of 123 genes and the model for end-stage liver disease (MELD) scores to assign patients to groups with poor survival (29% survived 90 days and 26% survived 180 days) and good survival (76% survived 90 days and 65% survived 180 days) (P < .001) in the derivation cohort. We named this assignment system the gene signature-MELD (gs-MELD) score. In validation cohort 1, the gs-MELD score discriminated patients with poor survival (43% survived 90 days) from those with good survival (96% survived 90 days) (P < .001). The gs-MELD score also discriminated between patients with a poor survival at 180 days (34% survived) and a good survival at 180 days (84% survived) (P < .001). The time-dependent area under the receiver operator characteristic curve for the score was 0.86 (95% confidence interval 0.73-0.99) for survival at 90 days, and 0.83 (95% confidence interval 0.71-0.96) for survival at 180 days. This score outperformed other clinical models to predict survival of patients with severe AH in validation cohort 1. In validation cohort 2, the gs-MELD discriminated patients with a poor survival at 90 days (12% survived) from those with a good survival at 90 days (100%) (P < .001).CONCLUSIONS:We integrated data on baseline liver gene expression pattern and the MELD score to create the gs-MELD scoring system, which identifies patients with severe AH, treated or not with corticosteroids, most and least likely to survive for 90 and 180 days.
- Full Text
- View/download PDF