Javier Ampuero1, Rocío Aller2, Rocío Gallego-Durán3, Javier Crespo4, José Luis Calleja5, Carmelo García-Monzón6, Judith Gómez-Camarero7, Joan Caballería8, Oreste Lo Iacono9, Luis Ibañez10, Javier García-Samaniego11, Agustín Albillos12, Rubén Francés13, Conrado Fernández-Rodríguez14, Moisés Diago15, Germán Soriano16, Raúl J Andrade17, Raquel Latorre18, Francisco Jorquera19, Rosa María Morillas20, Desamparados Escudero21, Pamela Estévez22, Manuel Hernández Guerra23, Salvador Augustín24, Jesús M Banales25, Patricia Aspichueta26, Salvador Benlloch27, José Miguel Rosales28, Javier Salmerón29, Juan Turnes30, Manuel Romero Gómez31. 1. Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain; SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain. Electronic address: jampuero-ibis@us.es. 2. Hospital Clínico Universitario de Valladolid, Centro de Investigación de Endocrinología y Nutrición, Universidad de Valladolid, Spain. 3. SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain. 4. Hospital Universitario Marqués de Valdecilla, Santander, Spain. 5. Hospital Universitario Puerta de Hierro, Madrid, Spain. 6. Liver Research Unit, Hospital Universitario Santa Cristina Instituto de Investigación Sanitaria Princesa Madrid, Spain. 7. Hospital Universitario de Burgos, Spain. 8. CIBERehd, Spain; Liver Unit. Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBPAS), Barcelona, Spain. 9. Hospital Universitario Tajo, Aranjuez, Spain. 10. CIBERehd, Spain; Hospital Gregorio Marañón, Madrid, Spain. 11. CIBERehd, Spain; Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. 12. CIBERehd, Spain; Hospital Universitario Ramón y Cajal, Madrid, Spain. 13. CIBERehd, Spain; Hospital General Universitario de Alicante, Universidad Miguel Hernández, Spain. 14. Hospital Universitario Fundación de Alcorcón, Universidad Rey Juan Carlos, Spain. 15. Hospital General Universitario de Valencia, Spain. 16. Hospital de la Santa Creu i San Pau, Barcelona, Spain. 17. CIBERehd, Spain; Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain. 18. Hospital Universitari Son Llátzer, Mallorca, Spain. 19. Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, IBIOMED y CIBERehd, León, España. 20. Hospital Germans Trias i Pujol, Badalona, Spain. 21. Hospital Clínico de Valencia, Spain. 22. Complejo Hospitalario Universitario de Vigo, Spain. 23. Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain. 24. Hospital Vall d'Hebrón, Barcelona, Spain. 25. CIBERehd, Spain; Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), Ikerbasque, San Sebastian, Spain. 26. Biocruces Research Institute, Barakaldo, Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, Leioa, Spain. 27. Hospital Universitari i Politecnic La Fe, Valencia, Spain. 28. Agencia Sanitaria Costa del Sol, Marbella, Spain. 29. Hospital Universitario San Cecilio, Granada, Spain. 30. Complejo Hospitalario de Pontevedra, Spain. 31. Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain; SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain. Electronic address: mromerogomez@us.es.
Abstract
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension [AHT], and dyslipidemia) in metabolically healthy patients. METHODS: We included 178 metabolically healthy-defined by the absence of baseline T2DM, AHT, dyslipidemia-patients with biopsy-proven NAFLD from the HEPAmet Registry (N = 1,030). Hepamet fibrosis score (HFS), NAFLD fibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia. RESULTS: During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19-7.31; p = 0.019), glucose levels (p = 0.008), age (p = 0.007) and BMI (p = 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14-5.10; p = 0.028), age (p = 0.0001), BMI (p = 0.006), glucose (p = 0.021) and platelets (p = 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% [4/16] vs. HFS <0.12 4.5% [4/88]; logRank 6.658, p = 0.010). CONCLUSION: Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLD fibrosis score or Fibrosis-4, predicted the occurrence of T2DM. LAY SUMMARY: Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.
BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension [AHT], and dyslipidemia) in metabolically healthy patients. METHODS: We included 178 metabolically healthy-defined by the absence of baseline T2DM, AHT, dyslipidemia-patients with biopsy-proven NAFLD from the HEPAmet Registry (N = 1,030). Hepamet fibrosis score (HFS), NAFLDfibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia. RESULTS: During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19-7.31; p = 0.019), glucose levels (p = 0.008), age (p = 0.007) and BMI (p = 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14-5.10; p = 0.028), age (p = 0.0001), BMI (p = 0.006), glucose (p = 0.021) and platelets (p = 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% [4/16] vs. HFS <0.12 4.5% [4/88]; logRank 6.658, p = 0.010). CONCLUSION: Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLDfibrosis score or Fibrosis-4, predicted the occurrence of T2DM. LAY SUMMARY:Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.
Authors: Giada Sebastiani; Keyur Patel; Vlad Ratziu; Jordan J Feld; Brent A Neuschwander-Tetri; Massimo Pinzani; Salvatore Petta; Annalisa Berzigotti; Peter Metrakos; Naglaa Shoukry; Elizabeth M Brunt; An Tang; Jeremy F Cobbold; Jean-Marie Ekoe; Karen Seto; Peter Ghali; Stéphanie Chevalier; Quentin M Anstee; Heather Watson; Harpreet Bajaj; James Stone; Mark G Swain; Alnoor Ramji Journal: Can Liver J Date: 2022-02-04
Authors: Giovanni Targher; Kathleen E Corey; Christopher D Byrne; Michael Roden Journal: Nat Rev Gastroenterol Hepatol Date: 2021-05-10 Impact factor: 46.802
Authors: Ivone Cristina Igreja Sá; Katarina Tripska; Milos Hroch; Radomir Hyspler; Alena Ticha; Hana Lastuvkova; Jolana Schreiberova; Eva Dolezelova; Samira Eissazadeh; Barbora Vitverova; Iveta Najmanova; Martina Vasinova; Miguel Pericacho; Stanislav Micuda; Petr Nachtigal Journal: Int J Mol Sci Date: 2020-11-27 Impact factor: 5.923