Javier Ampuero1, Raluca Pais2, Rocío Aller3, Rocío Gallego-Durán4, Javier Crespo5, Carmelo García-Monzón6, Jerome Boursier7, Eduardo Vilar8, Salvatore Petta9, Ming-Hua Zheng10, Desamparados Escudero11, Jose Luis Calleja12, Patricia Aspichueta13, Moisés Diago14, Jose Miguel Rosales15, Joan Caballería16, Judith Gómez-Camarero17, Oreste Lo Iacono18, Salvador Benlloch19, Agustín Albillos20, Juan Turnes21, Jesus M Banales22, Vlad Ratziu2, Manuel Romero-Gómez4. 1. Hospital Universitario Virgen del Rocío de Sevilla, Instituto de Biomedicina de Sevilla, University of Sevilla, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Sevilla, Spain. Electronic address: jampuero-ibis@us.es. 2. Hôpital Pitie Salpetriere, Université Pierre et Marie Curie, Paris, France. 3. Hospital Clínico Universitario de Valladolid, Centro de Investigación de Endocrinología y Nutrición, Universidad de Valladolid, Valladolid, Spain. 4. Hospital Universitario Virgen del Rocío de Sevilla, Instituto de Biomedicina de Sevilla, University of Sevilla, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Sevilla, Spain. 5. Hospital Universitario Marqués de Valdecilla, Santander, Spain. 6. Liver Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria Princesa, Madrid, Spain. 7. Hepatology Department, Angers University Hospital, Angers, France. 8. Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana. 9. Section of Gastroenterology and Hepatology, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy. 10. NAFLD Research Center, Department of Hepatology, the Affiliated Hospital of Wenzhou Medical University; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China. 11. Hospital Clínico de Valencia, Valencia, Spain. 12. Hospital Universitario Puerta de Hierro, Madrid, Spain. 13. Biocruces Research Institute, Barakaldo, Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country, Leioa, Spain. 14. Hospital General Universitario de Valencia, Valencia, Spain. 15. Agencia Sanitaria Costa del Sol, Marbella, Spain. 16. Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Barcelona, Spain. 17. Hospital Universitario de Burgos, Burgos, Spain. 18. Hospital Universitario Tajo, Aranjuez, Spain. 19. Hospital Universitari i Politecnic La Fe, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Valencia, Spain. 20. Hospital Universitario Ramón y Cajal, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Madrid, Spain. 21. Complejo Hospitalario de Pontevedra, Pontevedra, Spain. 22. Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute - Donostia University Hospital, University of the Basque Country, Ikerbasque, Biomedical Research Networking Center in Hepatic and Digestive Diseases, San Sebastián, Spain.
Abstract
BACKGROUND & AIMS: Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis. METHODS: We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n = 768) and validated the system using patients from Cuba (n = 344), Italy (n = 288), France (n = 830), and China (n = 232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios. RESULTS: Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P = .0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P < .05). CONCLUSIONS: Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis.
BACKGROUND & AIMS:Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis. METHODS: We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n = 768) and validated the system using patients from Cuba (n = 344), Italy (n = 288), France (n = 830), and China (n = 232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios. RESULTS: Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P = .0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P < .05). CONCLUSIONS: Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis.
Authors: Vanda Marques; Marta B Afonso; Nina Bierig; Filipa Duarte-Ramos; Álvaro Santos-Laso; Raul Jimenez-Agüero; Emma Eizaguirre; Luis Bujanda; Maria J Pareja; Rita Luís; Adília Costa; Mariana V Machado; Cristina Alonso; Enara Arretxe; José M Alustiza; Marcin Krawczyk; Frank Lammert; Dina G Tiniakos; Bertram Flehmig; Helena Cortez-Pinto; Jesus M Banales; Rui E Castro; Andrea Normann; Cecília M P Rodrigues Journal: Front Med (Lausanne) Date: 2021-06-23