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Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank

BACKGROUND: Obesity is among the main determinants of nonalcoholic fatty liver disease progression towards severe liver disease (SLD). However, risk factors for SLD in individuals with obesity have not been examined. OBJECTIVES: To identify the independent risk factors for SLD among participants wit...

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Autores principales: De Vincentis, Antonio, Tavaglione, Federica, Spagnuolo, Rocco, Pujia, Roberta, Tuccinardi, Dario, Mascianà, Gianluca, Picardi, Antonio, Antonelli Incalzi, Raffaele, Valenti, Luca, Romeo, Stefano, Vespasiani-Gentilucci, Umberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573310/
https://www.ncbi.nlm.nih.gov/pubmed/34750514
http://dx.doi.org/10.1038/s41366-021-01015-w
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author De Vincentis, Antonio
Tavaglione, Federica
Spagnuolo, Rocco
Pujia, Roberta
Tuccinardi, Dario
Mascianà, Gianluca
Picardi, Antonio
Antonelli Incalzi, Raffaele
Valenti, Luca
Romeo, Stefano
Vespasiani-Gentilucci, Umberto
author_facet De Vincentis, Antonio
Tavaglione, Federica
Spagnuolo, Rocco
Pujia, Roberta
Tuccinardi, Dario
Mascianà, Gianluca
Picardi, Antonio
Antonelli Incalzi, Raffaele
Valenti, Luca
Romeo, Stefano
Vespasiani-Gentilucci, Umberto
author_sort De Vincentis, Antonio
collection PubMed
description BACKGROUND: Obesity is among the main determinants of nonalcoholic fatty liver disease progression towards severe liver disease (SLD). However, risk factors for SLD in individuals with obesity have not been examined. OBJECTIVES: To identify the independent risk factors for SLD among participants with obesity from the UK Biobank. METHODS: A total of 80,224 UK Biobank participants with obesity (body mass index[BMI] > 30 kg/m(2)) and 242,822 without obesity, of European descent without clinical history of liver disease and liver cancer were prospectively followed for the onset of SLD, defined as a composite diagnosis of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation. Risk factors for incident SLD were assessed by Cox proportional hazards models. Different clinical phenotypes were derived by latent class analysis (LCA). RESULTS: Obesity conferred a 2.6-fold increased risk for SLD that was abolished after the inclusion of waist circumference (WC) in the model. Among individuals with obesity, age (adjusted hazard ratio [aHR] 1.05, 95%CI 1.03–1.07, p = 3.9 * 10(−7)), type 2 diabetes (aHR 2.18, 95%CI 1.55–3.05, p = 6.2 * 10(−6)), PNPLA3 rs738409 (aHR 1.59, 95%CI 1.33–1.9, p = 3.1 * 10(−7)) and WC (aHR 1.04, 95%CI 1.02–1.06, p = 8.5 * 10(−6)) were independent predictors of SLD. BMI category-specific WC thresholds allowed a better risk stratification compared to traditional ones. By LCA, the clinical phenotype at highest risk for SLD was that with BMI < 35 kg/m(2) and WC above BMI-category specific thresholds. CONCLUSIONS: Age, WC, type 2 diabetes, and the PNPLA3 variant are the main risk factors for SLD in individuals with obesity. WC is the principal mediator of SLD risk conveyed by increased BMI. BMI category-specific WC-thresholds may refine the SLD risk more accurately than traditional thresholds.
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spelling pubmed-85733102021-11-08 Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank De Vincentis, Antonio Tavaglione, Federica Spagnuolo, Rocco Pujia, Roberta Tuccinardi, Dario Mascianà, Gianluca Picardi, Antonio Antonelli Incalzi, Raffaele Valenti, Luca Romeo, Stefano Vespasiani-Gentilucci, Umberto Int J Obes (Lond) Article BACKGROUND: Obesity is among the main determinants of nonalcoholic fatty liver disease progression towards severe liver disease (SLD). However, risk factors for SLD in individuals with obesity have not been examined. OBJECTIVES: To identify the independent risk factors for SLD among participants with obesity from the UK Biobank. METHODS: A total of 80,224 UK Biobank participants with obesity (body mass index[BMI] > 30 kg/m(2)) and 242,822 without obesity, of European descent without clinical history of liver disease and liver cancer were prospectively followed for the onset of SLD, defined as a composite diagnosis of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation. Risk factors for incident SLD were assessed by Cox proportional hazards models. Different clinical phenotypes were derived by latent class analysis (LCA). RESULTS: Obesity conferred a 2.6-fold increased risk for SLD that was abolished after the inclusion of waist circumference (WC) in the model. Among individuals with obesity, age (adjusted hazard ratio [aHR] 1.05, 95%CI 1.03–1.07, p = 3.9 * 10(−7)), type 2 diabetes (aHR 2.18, 95%CI 1.55–3.05, p = 6.2 * 10(−6)), PNPLA3 rs738409 (aHR 1.59, 95%CI 1.33–1.9, p = 3.1 * 10(−7)) and WC (aHR 1.04, 95%CI 1.02–1.06, p = 8.5 * 10(−6)) were independent predictors of SLD. BMI category-specific WC thresholds allowed a better risk stratification compared to traditional ones. By LCA, the clinical phenotype at highest risk for SLD was that with BMI < 35 kg/m(2) and WC above BMI-category specific thresholds. CONCLUSIONS: Age, WC, type 2 diabetes, and the PNPLA3 variant are the main risk factors for SLD in individuals with obesity. WC is the principal mediator of SLD risk conveyed by increased BMI. BMI category-specific WC-thresholds may refine the SLD risk more accurately than traditional thresholds. Nature Publishing Group UK 2021-11-08 2022 /pmc/articles/PMC8573310/ /pubmed/34750514 http://dx.doi.org/10.1038/s41366-021-01015-w Text en © The Author(s), under exclusive licence to Springer Nature Limited 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
De Vincentis, Antonio
Tavaglione, Federica
Spagnuolo, Rocco
Pujia, Roberta
Tuccinardi, Dario
Mascianà, Gianluca
Picardi, Antonio
Antonelli Incalzi, Raffaele
Valenti, Luca
Romeo, Stefano
Vespasiani-Gentilucci, Umberto
Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank
title Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank
title_full Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank
title_fullStr Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank
title_full_unstemmed Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank
title_short Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank
title_sort metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the uk biobank
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573310/
https://www.ncbi.nlm.nih.gov/pubmed/34750514
http://dx.doi.org/10.1038/s41366-021-01015-w
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