PMID- 32147361
OWN - NLM
STAT- MEDLINE
DCOM- 20211105
LR  - 20211105
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Linking)
VI  - 73
IP  - 1
DP  - 2020 Jul
TI  - Significant fibrosis predicts new-onset diabetes mellitus and arterial 
      hypertension in patients with NASH.
PG  - 17-25
LID - S0168-8278(20)30127-6 [pii]
LID - 10.1016/j.jhep.2020.02.028 [doi]
AB  - 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.
CI  - Copyright (c) 2020 European Association for the Study of the Liver. Published by 
      Elsevier B.V. All rights reserved.
FAU - Ampuero, Javier
AU  - Ampuero J
AD  - Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Sevilla, Spain; 
      SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain. 
      Electronic address: jampuero-ibis@us.es.
FAU - Aller, Rocio
AU  - Aller R
AD  - Hospital Clinico Universitario de Valladolid, Centro de Investigacion de 
      Endocrinologia y Nutricion, Universidad de Valladolid, Spain.
FAU - Gallego-Duran, Rocio
AU  - Gallego-Duran R
AD  - SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain.
FAU - Crespo, Javier
AU  - Crespo J
AD  - Hospital Universitario Marques de Valdecilla, Santander, Spain.
FAU - Calleja, Jose Luis
AU  - Calleja JL
AD  - Hospital Universitario Puerta de Hierro, Madrid, Spain.
FAU - Garcia-Monzon, Carmelo
AU  - Garcia-Monzon C
AD  - Liver Research Unit, Hospital Universitario Santa Cristina Instituto de 
      Investigacion Sanitaria Princesa Madrid, Spain.
FAU - Gomez-Camarero, Judith
AU  - Gomez-Camarero J
AD  - Hospital Universitario de Burgos, Spain.
FAU - Caballeria, Joan
AU  - Caballeria J
AD  - CIBERehd, Spain; Liver Unit. Hospital Clinic, Institut d'Investigacions 
      Biomediques August Pi i Sunyer (IDIBPAS), Barcelona, Spain.
FAU - Lo Iacono, Oreste
AU  - Lo Iacono O
AD  - Hospital Universitario Tajo, Aranjuez, Spain.
FAU - Ibanez, Luis
AU  - Ibanez L
AD  - CIBERehd, Spain; Hospital Gregorio Maranon, Madrid, Spain.
FAU - Garcia-Samaniego, Javier
AU  - Garcia-Samaniego J
AD  - CIBERehd, Spain; Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
FAU - Albillos, Agustin
AU  - Albillos A
AD  - CIBERehd, Spain; Hospital Universitario Ramon y Cajal, Madrid, Spain.
FAU - Frances, Ruben
AU  - Frances R
AD  - CIBERehd, Spain; Hospital General Universitario de Alicante, Universidad Miguel 
      Hernandez, Spain.
FAU - Fernandez-Rodriguez, Conrado
AU  - Fernandez-Rodriguez C
AD  - Hospital Universitario Fundacion de Alcorcon, Universidad Rey Juan Carlos, Spain.
FAU - Diago, Moises
AU  - Diago M
AD  - Hospital General Universitario de Valencia, Spain.
FAU - Soriano, German
AU  - Soriano G
AD  - Hospital de la Santa Creu i San Pau, Barcelona, Spain.
FAU - Andrade, Raul J
AU  - Andrade RJ
AD  - CIBERehd, Spain; Unidad de Gestion Clinica de Enfermedades Digestivas, Instituto 
      de Investigacion Biomedica de Malaga-IBIMA, Hospital Universitario Virgen de la 
      Victoria, Universidad de Malaga, Malaga, Spain.
FAU - Latorre, Raquel
AU  - Latorre R
AD  - Hospital Universitari Son Llatzer, Mallorca, Spain.
FAU - Jorquera, Francisco
AU  - Jorquera F
AD  - Servicio de Aparato Digestivo, Complejo Asistencial Universitario de Leon, 
      IBIOMED y CIBERehd, Leon, Espana.
FAU - Morillas, Rosa Maria
AU  - Morillas RM
AD  - Hospital Germans Trias i Pujol, Badalona, Spain.
FAU - Escudero, Desamparados
AU  - Escudero D
AD  - Hospital Clinico de Valencia, Spain.
FAU - Estevez, Pamela
AU  - Estevez P
AD  - Complejo Hospitalario Universitario de Vigo, Spain.
FAU - Guerra, Manuel Hernandez
AU  - Guerra MH
AD  - Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
FAU - Augustin, Salvador
AU  - Augustin S
AD  - Hospital Vall d'Hebron, Barcelona, Spain.
FAU - Banales, Jesus M
AU  - Banales JM
AD  - 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.
FAU - Aspichueta, Patricia
AU  - Aspichueta P
AD  - Biocruces Research Institute, Barakaldo, Department of Physiology, Faculty of 
      Medicine and Nursing, University of Basque Country UPV/EHU, Leioa, Spain.
FAU - Benlloch, Salvador
AU  - Benlloch S
AD  - Hospital Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Rosales, Jose Miguel
AU  - Rosales JM
AD  - Agencia Sanitaria Costa del Sol, Marbella, Spain.
FAU - Salmeron, Javier
AU  - Salmeron J
AD  - Hospital Universitario San Cecilio, Granada, Spain.
FAU - Turnes, Juan
AU  - Turnes J
AD  - Complejo Hospitalario de Pontevedra, Spain.
FAU - Romero Gomez, Manuel
AU  - Romero Gomez M
AD  - Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Sevilla, Spain; 
      SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain. 
      Electronic address: mromerogomez@us.es.
CN  - HEPAmet Registry
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200306
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
SB  - IM
EIN - J Hepatol. 2020 Sep;73(3):740-741. PMID: 32654856
CIN - J Hepatol. 2021 Apr;74(4):970-971. PMID: 33340576
CIN - J Hepatol. 2021 Apr;74(4):971-972. PMID: 33359898
MH  - Adult
MH  - Biopsy/methods
MH  - *Diabetes Mellitus, Type 2/diagnosis/epidemiology
MH  - Disease Progression
MH  - Dyslipidemias/blood/diagnosis/epidemiology
MH  - Female
MH  - Humans
MH  - *Hypertension/diagnosis/epidemiology
MH  - Incidence
MH  - Liver/*pathology
MH  - *Liver Cirrhosis/diagnosis/etiology/metabolism/physiopathology
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - *Non-alcoholic Fatty Liver Disease/complications/epidemiology/metabolism
MH  - Prognosis
MH  - Risk Assessment
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - Spain/epidemiology
OTO - NOTNLM
OT  - Arterial hypertension
OT  - Diabetes mellitus
OT  - Fibrosis
OT  - Hepamet score
OT  - NAFLD
COIS- 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.
EDAT- 2020/03/10 06:00
MHDA- 2021/11/06 06:00
CRDT- 2020/03/10 06:00
PHST- 2019/09/12 00:00 [received]
PHST- 2020/02/18 00:00 [revised]
PHST- 2020/02/20 00:00 [accepted]
PHST- 2020/03/10 06:00 [pubmed]
PHST- 2021/11/06 06:00 [medline]
PHST- 2020/03/10 06:00 [entrez]
AID - S0168-8278(20)30127-6 [pii]
AID - 10.1016/j.jhep.2020.02.028 [doi]
PST - ppublish
SO  - J Hepatol. 2020 Jul;73(1):17-25. doi: 10.1016/j.jhep.2020.02.028. Epub 2020 Mar 
      6.