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12 pages, 594 KiB

Open AccessArticle

Fatty Liver Disease in Patients with Prediabetes and Overweight or Obesity

by María Arias-Fernández, Sergio Fresneda, Manuela Abbate, Marina Torres-Carballo, Aina Huguet-Torres, Cristian Sánchez-Rodríguez, Miquel Bennasar-Veny, Aina M. Yañez and Carla Busquets-Cortés

Metabolites 2023, 13(4), 531; https://doi.org/10.3390/metabo13040531 - 7 Apr 2023

Cited by 1 | Viewed by 1627

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a global health problem associated with liver morbimortality, obesity, and type 2 diabetes mellitus. This study aimed to analyze the prevalence of NAFLD (defined as a fatty liver index [FLI] ≥ 60) and its association with other [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem associated with liver morbimortality, obesity, and type 2 diabetes mellitus. This study aimed to analyze the prevalence of NAFLD (defined as a fatty liver index [FLI] ≥ 60) and its association with other cardiovascular risk (CVR) factors in patients with prediabetes and overweight/obesity. The present cross-sectional analysis uses baseline data from an ongoing randomized clinical trial. Sociodemographic and anthropometric characteristics, CVR (assessed by the REGICOR-Framingham risk equation), metabolic syndrome (MetS), and FLI-defined NAFLD (cut-off value of ≥60) were assessed. The prevalence of FLI-defined NAFLD was 78% overall. Men exhibited a worse cardiometabolic profile as compared to women, specifically, with higher values of systolic blood pressure (137.02 ± 13.48 vs. 131.22 ± 14.77 mmHg), diastolic blood pressure (85.33 ± 9.27 vs. 82.3 ± 9.12 mmHg), aspartate aminotransferase (AST) (27.23 ± 12.15 vs. 21.23 ± 10.05 IU/L), alanine aminotransferase (ALT) (34.03 ± 23.31 vs. 21.73 ± 10.80 IU/L), and higher CVR (5.58 ± 3.16 vs. 3.60 ± 1.68). FLI-defined NAFLD was associated with elevated AST, ALT, and the presence of MetS (73.7%) and CVR for the whole sample. People with prediabetes present a high burden of comorbidities related to CVR, despite clinical follow-up, and it is recommended to actively begin working with them to reduce their risks. Full article

(This article belongs to the Special Issue Fatty Liver Index and Progression to Diabetes in Patients with Metabolic Syndrome)

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16 pages, 815 KiB

Open AccessArticle

The Triangle of Nonalcoholic Fatty Liver Disease, Metabolic Dysfunction, and Periodontitis: Analysis of the Dental, Oral, Medical and Epidemiological (DOME) Records-Based Nationwide Research

by Doron Ram, Asaf Wilensky, Dorit Zur and Galit Almoznino

Metabolites 2022, 12(12), 1212; https://doi.org/10.3390/metabo12121212 - 2 Dec 2022

Cited by 4 | Viewed by 1851

Abstract

This study aimed to analyze the associations of nonalcoholic fatty liver disease (NAFLD) with dental parameters, while controlling for socio-demographics, health-related habits, and each of the metabolic syndrome (MetS) components, consequences, and related conditions among a nationally representative sample of young and middle-aged [...] Read more.

This study aimed to analyze the associations of nonalcoholic fatty liver disease (NAFLD) with dental parameters, while controlling for socio-demographics, health-related habits, and each of the metabolic syndrome (MetS) components, consequences, and related conditions among a nationally representative sample of young and middle-aged adults. To that end, we analyzed data from the dental, oral, medical epidemiological (DOME) cross-sectional records-based study that combined comprehensive socio-demographic, medical, and dental databases of a nationally representative sample of military personnel. Included were 132,529 subjects aged 18–50 who attended military dental clinics for one year. The prevalence of NAFLD in the study population was 0.7% (938/132,529). The following parameters maintained a statistically positive association with NAFLD in the multivariate analysis (from highest to lowest OR): male sex (OR = 3.91 (2.29–6.66)), hyperlipidemia (OR = 3.69 (2.75–4.95)), diabetes Type 2 (OR = 3.14 (2.21–4.46)), hypertension (OR = 1.67 (1.30–2.14)), periodontitis (OR = 1.42 (1.06–1.89)), body mass index (BMI) (OR = 1.15 (1.13–1.18)), and age (OR = 1.08 (1.06–1.09)). The multivariate analysis established a profile of the “patient vulnerable to NAFLD”, including older age, male sex, and other MetS components, including diabetes type 2, hypertension, hyperlipidemia, BMI, and periodontitis. This profile aligns with the current new definition of metabolic dysfunction-associated fatty liver disease (MAFLD). We also analyzed the associations of the sum of the standard dental unit (SDU) scores of planned (SDU-P) and delivered (SDU-D) dental procedures per patient with NAFLD using receiver operating characteristic (ROC) analysis. The SDU-P (planned) score exhibited excellent discrimination for NAFLD (area under the curve (AUC) = 0.718 (0.703–0.734)). Overall, the results confirmed the hypothesis of this research, i.e., that NAFLD is associated with dental morbidity, particularly with periodontitis. Full article

(This article belongs to the Special Issue Fatty Liver Index and Progression to Diabetes in Patients with Metabolic Syndrome)

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11 pages, 678 KiB

Open AccessArticle

Relationship between Insulin Resistance Risk Scales and Non-Alcoholic Fatty Liver Disease and Liver Fibrosis Scales in 219,477 Spanish Workers

by José Ignacio Ramírez-Manent, Emilio Martínez-Almoyna, Carlos López, Carla Busquets-Cortés, Hilda González San Miguel and Ángel Arturo López-González

Metabolites 2022, 12(11), 1093; https://doi.org/10.3390/metabo12111093 - 10 Nov 2022

Cited by 2 | Viewed by 1093

Abstract

Insulin resistance (IR) has been identified as a key factor in the appearance of non-alcoholic fatty liver disease (NAFLD) as it is related through a complex molecular biochemical and immunological mechanism. Our aim was to evaluate the relationship between different scales that estimate [...] Read more.

Insulin resistance (IR) has been identified as a key factor in the appearance of non-alcoholic fatty liver disease (NAFLD) as it is related through a complex molecular biochemical and immunological mechanism. Our aim was to evaluate the relationship between different scales that estimate the risk of IR and scales that determine the risk of NAFLD. This descriptive and cross-sectional study was performed in 219,477 Spanish workers from different sectors and Spanish regions. The prevalence of high values of all the IR scales increases as the values of the NAFLD and liver fibrosis scales increase. In the multivariate analysis, the risk of presenting high values in the IR scales increases greatly as the values of the NAFLD and hepatic fibrosis scales increase, with particularly high OR values when using the Metabolic Score for Insulin Resistance (METS-IR) scale (LAP high OR 42.20 (95% CI (39.10–45.56) and FLI high OR 32.35 (95% CI 31.10–33.61)). We can conclude that there is a direct relationship between the values of the IR scales and the NAFLD and liver fibrosis scales in our population. Full article

(This article belongs to the Special Issue Fatty Liver Index and Progression to Diabetes in Patients with Metabolic Syndrome)

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12 pages, 1549 KiB

Open AccessArticle

Metabolic Dysfunction-Associated Fatty Liver Disease in the National Health and Nutrition Examination Survey 2017–2020: Epidemiology, Clinical Correlates, and the Role of Diagnostic Scores

by Panagiotis Theofilis, Aikaterini Vordoni and Rigas G. Kalaitzidis

Metabolites 2022, 12(11), 1070; https://doi.org/10.3390/metabo12111070 - 5 Nov 2022

Cited by 6 | Viewed by 1534

Abstract

The recent establishment of metabolic dysfunction-associated fatty liver disease (MAFLD) has led to a reevaluation of its epidemiology, diagnosis, and clinical implications. In this study, we aimed to evaluate MAFLD’s epidemiology and its association with other pathologic states and biomarkers, as well as [...] Read more.

The recent establishment of metabolic dysfunction-associated fatty liver disease (MAFLD) has led to a reevaluation of its epidemiology, diagnosis, and clinical implications. In this study, we aimed to evaluate MAFLD’s epidemiology and its association with other pathologic states and biomarkers, as well as to assess the prevalence of the different fibrosis stages in the MAFLD population, together with the importance of diagnostic scores in the preliminary determination of significant fibrosis. After analyzing the National Health and Nutrition Examination Survey (NHANES) 2017–2020, we found a high prevalence of MAFLD, at 58.6% of the studied population. MAFLD was accompanied by numerous comorbidities, which were increasingly common in individuals with higher grades of liver fibrosis. Fatty liver index emerged as a reliable indicator of MAFLD, as well as significant fibrosis. The estimation of fatty liver index could be a reasonable addition to the evaluation of patients with metabolic risk factors and could lead a diagnosis in the absence of liver elastography or biopsy. Further studies are needed to enhance our knowledge regarding its prognosis, as well as the role of novel therapies in its prevention or regression. Full article

(This article belongs to the Special Issue Fatty Liver Index and Progression to Diabetes in Patients with Metabolic Syndrome)

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10 pages, 1522 KiB

Open AccessEditor’s ChoiceArticle

Liver Fetuin-A at Initiation of Insulin Resistance

by Nicolas Lanthier, Valérie Lebrun, Olivier Molendi-Coste, Nico van Rooijen and Isabelle A. Leclercq

Metabolites 2022, 12(11), 1023; https://doi.org/10.3390/metabo12111023 - 25 Oct 2022

Cited by 9 | Viewed by 1783

Abstract

Hepatokines (liver secreted proteins with possible distant action) are emerging potential players in insulin resistance in type 2 diabetic patients. Here, we explored the effect of a high-fat diet on the expression of fetuin-A, one of those candidate liver proteins, and its relationship [...] Read more.

Hepatokines (liver secreted proteins with possible distant action) are emerging potential players in insulin resistance in type 2 diabetic patients. Here, we explored the effect of a high-fat diet on the expression of fetuin-A, one of those candidate liver proteins, and its relationship with liver macrophage activation. Mice were fed a normal diet or a high-fat diet for 3 days, known to initiate steatosis and liver insulin resistance. A preventive liver macrophage depletion was obtained by intravenous injection of clodronate-loaded liposomes. The mRNA and protein expression of fetuin-A was evaluated by qPCR, Western blot and immunofluorescence on different insulin-sensitive tissues (liver, adipose tissue, and muscle). Short-term high-fat diet-induced steatosis, liver macrophage activation, and hepatic insulin resistance together with a significantly increased expression of liver AHSG (α2-HS glycoprotein/fetuin-A) mRNA and serum fetuin-A concentration. On immunofluorescence, fetuin-A was mostly expressed in centrilobular hepatocytes. This increase in fetuin-A under high-fat diet was not evidenced in other peripheral insulin-sensitive tissues (skeletal muscle and adipose tissue). The mRNA expression of α2-HS glycoprotein was 800 times higher within the liver compared with the adipose tissue or the muscle. Liver macrophage depletion that significantly ameliorated insulin sensitivity was associated with a significant decrease in α2-HS glycoprotein mRNA expression. In conclusion, this study demonstrated liver fetuin-A overexpression at the initiation of high-fat diet feeding, concurrent with hepatic steatosis and insulin resistance. Targeting liver macrophages in this setting reduced liver α2-HS glycoprotein expression suggesting that fetuin-A acts as an hepatokine with proinsulin resistance effects. Full article

(This article belongs to the Special Issue Fatty Liver Index and Progression to Diabetes in Patients with Metabolic Syndrome)

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15 pages, 2854 KiB

Open AccessArticle

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats

by Lorena de Souza Almeida, Caio Jordão Teixeira, Carolina Vieira Campos, Laís Guadalupe Casaloti, Frhancielly Shirley Sodré, Vinícius Cooper Capetini, Andressa Godoy Amaral, Tanyara Baliani Payolla, Lucas Carminatti Pantaleão, Gabriel Forato Anhê and Silvana Bordin

Metabolites 2022, 12(10), 886; https://doi.org/10.3390/metabo12100886 - 21 Sep 2022

Cited by 3 | Viewed by 1744

Abstract

Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during [...] Read more.

Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In the present study, we demonstrate that the combination of IUGR and fructose treatment during adulthood also results in increased hepatic myeloperoxidase (MPO) activity, AKT phosphorylation and serum aspartate transaminase. Growth-restricted rats also presented reduced hepatic TRIB3 and GADD45a after fructose treatment. Other markers of cell proliferation, such as Cyclin D, PCNA, Hgf and Hspa4/Hsp70 expression and the number of Ki-67 positive cells, were all increased in the liver of growth- restricted rats treated with fructose. On the other hand, the combination of IUGR and fructose treatment during adult life reduced the levels of IGF-1. In conclusion, our data indicate that after exposure to fructose, adult rats subjected to dexamethasone-induced IUGR display exacerbated molecular changes in markers of NASH and HCC. Full article

(This article belongs to the Special Issue Fatty Liver Index and Progression to Diabetes in Patients with Metabolic Syndrome)

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10 pages, 629 KiB

Open AccessFeature PaperArticle

Comparison of the Diagnostic Performance of Steatosis Indices for Discrimination of CT-Diagnosed Metabolic Dysfunction-Associated Fatty Liver Disease

by A. Lum Han and Hee Kyung Lee

Metabolites 2022, 12(7), 664; https://doi.org/10.3390/metabo12070664 - 19 Jul 2022

Cited by 13 | Viewed by 1851

Abstract

Non-alcoholic fatty liver disease (NAFLD) was redefined as metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020. Due to this, further validation of the non-invasive tests used in NAFLD diagnosis is required for MAFLD. There are five known steatosis indices for computed tomography (CT)-diagnosed [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) was redefined as metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020. Due to this, further validation of the non-invasive tests used in NAFLD diagnosis is required for MAFLD. There are five known steatosis indices for computed tomography (CT)-diagnosed MAFLD. These indices include the fatty liver index (FLI), the hepatic steatosis index (HSI), the lipid accumulation product (LAP), the visceral adiposity index (VAI), and the Zhejiang University index (ZJU). We aimed to analyze the diagnostic abilities of these five widely known steatosis indices for CT-diagnosed MAFLD. From March 2012 to October 2019, we retrospectively analyzed the clinical information and images of 1300 adults aged ≥19 years who underwent CT scans at our institution. To compare differences, the Chi-square test and independent t-test were used for categorical and continuous variables, respectively. The area under the receiver operating characteristic (AUROC) curve was used to validate the diagnostic accuracy of MAFLD. Of the five indices, FLI was the best at predicting MAFLD, with the highest AUROC (0.791). The sensitivity and specificity of FLI for diagnosing MAFLD were both 70.9%. The optimal cut-off value was 29.9. FLI is a useful surrogate index for screening MAFLD in clinical practice. Full article

(This article belongs to the Special Issue Fatty Liver Index and Progression to Diabetes in Patients with Metabolic Syndrome)

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21 pages, 717 KiB

Open AccessSystematic Review

Therapeutic Physical Exercise Programs in the Context of NASH Cirrhosis and Liver Transplantation: A Systematic Review

by Marwin A. Farrugia, Sebastien Le Garf, Andrea Chierici, Thierry Piche, Philippe Gual, Antonio Iannelli and Rodolphe Anty

Metabolites 2023, 13(3), 330; https://doi.org/10.3390/metabo13030330 - 23 Feb 2023

Cited by 6 | Viewed by 2011

Abstract

In recent years, various physical exercise interventions have been developed with a view to reducing comorbidity and morbidity rates among patients with chronic diseases. Regular physical exercise has been shown to reduce hypertension and mortality in patients with type 2 diabetes. Diabetes and [...] Read more.

In recent years, various physical exercise interventions have been developed with a view to reducing comorbidity and morbidity rates among patients with chronic diseases. Regular physical exercise has been shown to reduce hypertension and mortality in patients with type 2 diabetes. Diabetes and obesity are often associated with the development of nonalcoholic fatty liver disease, which can lead to liver fibrosis and then (in some cases) nonalcoholic steatohepatitis cirrhosis. We searched the literature for publications on personalized physical exercise programs in cirrhotic patients before and after liver transplantation. Eleven studies in cirrhotic patients and one study in liver transplant recipients were included in the systematic review, the results of which were reported in compliance with the preferred reporting items for systematic reviews and meta-analyses guidelines. The personalized physical exercise programs lasted for 6 to 16 weeks. Our review evidenced improvements in peak oxygen consumption and six-minute walk test performance and a reduction in the hepatic venous pressure gradient. In cirrhotic patients, personalized physical exercise programs improve quality of life, are not associated with adverse effects, and (for transplant recipients) might reduce the 90-day hospital readmission rate. However, none of the literature data evidenced reductions in the mortality rates before and after transplantation. Further prospective studies are needed to evaluate the benefit of long-term physical exercise programs in cirrhotic patients before and after liver transplantation. Full article

(This article belongs to the Special Issue Fatty Liver Index and Progression to Diabetes in Patients with Metabolic Syndrome)

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