Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH.


Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
07 2020
Historique:
received: 12 09 2019
revised: 18 02 2020
accepted: 20 02 2020
pubmed: 10 3 2020
medline: 6 11 2021
entrez: 10 3 2020
Statut: ppublish

Résumé

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. 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. 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). 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 32147361
pii: S0168-8278(20)30127-6
doi: 10.1016/j.jhep.2020.02.028
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

17-25

Commentaires et corrections

Type : ErratumIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Auteurs

Javier Ampuero (J)

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.

Rocío Aller (R)

Hospital Clínico Universitario de Valladolid, Centro de Investigación de Endocrinología y Nutrición, Universidad de Valladolid, Spain.

Rocío Gallego-Durán (R)

SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain.

Javier Crespo (J)

Hospital Universitario Marqués de Valdecilla, Santander, Spain.

José Luis Calleja (JL)

Hospital Universitario Puerta de Hierro, Madrid, Spain.

Carmelo García-Monzón (C)

Liver Research Unit, Hospital Universitario Santa Cristina Instituto de Investigación Sanitaria Princesa Madrid, Spain.

Judith Gómez-Camarero (J)

Hospital Universitario de Burgos, Spain.

Joan Caballería (J)

CIBERehd, Spain; Liver Unit. Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBPAS), Barcelona, Spain.

Oreste Lo Iacono (O)

Hospital Universitario Tajo, Aranjuez, Spain.

Luis Ibañez (L)

CIBERehd, Spain; Hospital Gregorio Marañón, Madrid, Spain.

Javier García-Samaniego (J)

CIBERehd, Spain; Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.

Agustín Albillos (A)

CIBERehd, Spain; Hospital Universitario Ramón y Cajal, Madrid, Spain.

Rubén Francés (R)

CIBERehd, Spain; Hospital General Universitario de Alicante, Universidad Miguel Hernández, Spain.

Conrado Fernández-Rodríguez (C)

Hospital Universitario Fundación de Alcorcón, Universidad Rey Juan Carlos, Spain.

Moisés Diago (M)

Hospital General Universitario de Valencia, Spain.

Germán Soriano (G)

Hospital de la Santa Creu i San Pau, Barcelona, Spain.

Raúl J Andrade (RJ)

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.

Raquel Latorre (R)

Hospital Universitari Son Llátzer, Mallorca, Spain.

Francisco Jorquera (F)

Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, IBIOMED y CIBERehd, León, España.

Rosa María Morillas (RM)

Hospital Germans Trias i Pujol, Badalona, Spain.

Desamparados Escudero (D)

Hospital Clínico de Valencia, Spain.

Pamela Estévez (P)

Complejo Hospitalario Universitario de Vigo, Spain.

Manuel Hernández Guerra (MH)

Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.

Salvador Augustín (S)

Hospital Vall d'Hebrón, Barcelona, Spain.

Jesús M Banales (JM)

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.

Patricia Aspichueta (P)

Biocruces Research Institute, Barakaldo, Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, Leioa, Spain.

Salvador Benlloch (S)

Hospital Universitari i Politecnic La Fe, Valencia, Spain.

José Miguel Rosales (JM)

Agencia Sanitaria Costa del Sol, Marbella, Spain.

Javier Salmerón (J)

Hospital Universitario San Cecilio, Granada, Spain.

Juan Turnes (J)

Complejo Hospitalario de Pontevedra, Spain.

Manuel Romero Gómez (M)

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.

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Classifications MeSH