Special Issue "Non-alcoholic Fatty Liver Disease: From Lifestyle to Environmental Factors"

Special Issue Editors

Dr. Bruno Ramos-Molina
E-Mail Website
Leading Guest Editor
Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain
Interests: metabolism; obesity; diabetes; non-alcoholic fatty liver disease; nutrition; microbiota; metabolomics; epigenetics
Dr. Fernando Cardona
E-Mail Website
Assistant Guest Editor
Institute of Biomedical Research in Malaga (IBIMA), 29010 Malaga, Spain
Interests: obesity; nutrition; epigenetics; postprandial lipemia; lipoproteins; microbiota; epigenetics

Special Issue Information

Dear Colleagues,

Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease worldwide. NAFLD is currently the most prevalent liver disease in the population, due to its strong relationship with obesity and its comorbidities. NAFLD represents a spectrum of liver conditions ranging from simple steatosis (a relatively benign condition) to non-alcoholic steatohepatitis, which could result in fibrosis and ultimately to cirrhosis or hepatocarcinoma. It is widely accepted that weight management interventions (i.e., diet and exercise) are the most effective strategies for NAFLD resolution in patients with obesity. In addition, a growing body of evidence suggests that the physiopathology of NAFLD is highly influenced by several exogenous and environmental factors such as aging, excessive intake of calories, processed food, lower intake of anti-oxidant vitamins, and sedentary lifestyle. These factors could participate in the development or progression of the disease by inducing changes in gut microbiota and/or epigenetic modifications, among other mechanisms. This Special Issue seeks research papers on the impact of lifestyle and environmental factors on the pathogenesis of NAFLD.

We welcome original research papers using different study designs as well as systematic reviews and meta-analyses.

Dr. Bruno Ramos-Molina
Leading Guest Editor

Dr. Fernando Cardona
Assistant Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Environmental Research and Public Health is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2300 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • obesity
  • non-alcoholic fatty liver disease
  • non-alcoholic steatohepatitis
  • lifestyle
  • environmental factors
  • diet
  • microbiota
  • epigenetics

Published Papers (6 papers)

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Research

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Article
Assessing Interactions between PNPLA3 and Dietary Intake on Liver Steatosis in Mexican-Origin Adults
Int. J. Environ. Res. Public Health 2021, 18(13), 7055; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18137055 - 01 Jul 2021
Viewed by 431
Abstract
Mexican-origin (MO) adults have among the highest rates of nonalcoholic fatty liver disease (NAFLD) placing them at increased risk of liver cancer. Evidence suggests that a single nucleotide polymorphism (SNP) in the PNPLA3 gene, rs738409, increases the risk and progression of NAFLD and [...] Read more.
Mexican-origin (MO) adults have among the highest rates of nonalcoholic fatty liver disease (NAFLD) placing them at increased risk of liver cancer. Evidence suggests that a single nucleotide polymorphism (SNP) in the PNPLA3 gene, rs738409, increases the risk and progression of NAFLD and may modify the relationship between certain dietary factors and liver steatosis. The purpose of this study was to identify whether interactions exist between specific dietary factors and rs738409 genotype status among MO adults in relation to levels of liver steatosis. We analyzed cross-sectional data from a sample of 288 MO adults. Participants completed at least two 24-h dietary recalls. Multiple linear regression was performed assuming an additive genetic model to test the main effects of several dietary variables on levels of hepatic steatosis, adjusting for covariates. To test for effect modification, the product of the genotype and the dietary variable was included as a covariate in the model. No significant association between dietary intake and level of hepatic steatosis was observed, nor any significant gene-diet interactions. Our findings suggest that dietary intake may have the same magnitude of protective or deleterious effect even among MO adults with high genetic risk for NAFLD and NAFLD progression. Full article
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Article
The Association between Decreased Kidney Function and FIB-4 Index Value, as Indirect Liver Fibrosis Indicator, in Middle-Aged and Older Subjects
Int. J. Environ. Res. Public Health 2021, 18(13), 6980; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18136980 - 29 Jun 2021
Viewed by 473
Abstract
Liver fibrosis might be linked to the prevalence of chronic kidney disease (CKD). However, there is little information about the association between liver fibrosis and decreased kidney function in middle-aged and older subjects. We aimed to evaluate the influence of liver fibrosis on [...] Read more.
Liver fibrosis might be linked to the prevalence of chronic kidney disease (CKD). However, there is little information about the association between liver fibrosis and decreased kidney function in middle-aged and older subjects. We aimed to evaluate the influence of liver fibrosis on the incidence or prevalence of CKD stage 3–5 in a retrospective cross-sectional study (Study 1, n = 806) and a 6-year longitudinal study (Study 2, n = 380) of middle-aged and older subjects. We evaluated liver fibrosis using the Fibrosis-4 (FIB-4) index and kidney function using the estimated glomerular filtration rate (eGFR) of all subjects. All subjects were divided into four groups on the basis of their FIB-4 score quartiles (low to high). In the Jonckheere–Terpstra trend test of Study 1, the eGFR decreased significantly from the lowest group to the highest group (p < 0.001). The Kaplan–Meier survival curve in Study 2 showed that the cumulative prevalence of CKD stage 3–5 was higher in the third quartile than the other quartiles. Our results suggest that liver fibrosis could be a useful indicator for the prevalence of CKD, even within a relatively healthy population, although liver fibrosis was not an independent risk factor. Full article
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Article
Urinary Phthalate Levels Associated with the Risk of Nonalcoholic Fatty Liver Disease in Adults: The Korean National Environmental Health Survey (KoNEHS) 2012–2014
Int. J. Environ. Res. Public Health 2021, 18(11), 6035; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18116035 - 04 Jun 2021
Viewed by 598
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Recent experimental studies suggested that phthalates might induce NAFLD. Therefore, this study aimed to investigate the relationship between phthalates metabolites and NAFLD in the human population. This cross-sectional analysis was performed using [...] Read more.
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Recent experimental studies suggested that phthalates might induce NAFLD. Therefore, this study aimed to investigate the relationship between phthalates metabolites and NAFLD in the human population. This cross-sectional analysis was performed using data from the Korean National Environmental Health Survey II (2012–2014) among Korean adults (n = 5800). NAFLD was diagnosed using the hepatic steatosis index (HSI) in the absence of other causes of chronic liver diseases. Among the participants (mean age 46 years, 47.5% male), the prevalence of NAFLD was associated with urinary levels of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-benzyl phthalate (MBzP), and mono-n-butyl phthalate (MnBP) compared to the reference group. In the multivariate model, the odds ratios (ORs), 95% confidence interval (CI) for NAFLD were 1.33 (1.00–1.78) and 1.39 (1.00–1.92) in the 3rd and 4th quartile of MEHHP, respectively. Based on the study findings, high levels of urinary phthalates are associated with the prevalence of NAFLD in Korean adults. Further investigation is required to elucidate the causal relationship. Full article
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Article
Quality of Life and Coping in Nonalcoholic Fatty Liver Disease: Influence of Diabetes and Obesity
Int. J. Environ. Res. Public Health 2021, 18(7), 3503; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18073503 - 28 Mar 2021
Cited by 1 | Viewed by 722
Abstract
Our aim was to analyze how type 2 diabetes and obesity influence quality of life (QoL) and coping in patients with nonalcoholic fatty liver disease (NAFLD), and which coping strategies predict diabetic or obese participants’ QoL. QoL (SF-12, CLDQ-NAFLD) and coping strategies (COPE-28) [...] Read more.
Our aim was to analyze how type 2 diabetes and obesity influence quality of life (QoL) and coping in patients with nonalcoholic fatty liver disease (NAFLD), and which coping strategies predict diabetic or obese participants’ QoL. QoL (SF-12, CLDQ-NAFLD) and coping strategies (COPE-28) were evaluated in 307 biopsy-proven NAFLD patients with absence or presence of diabetes or obesity. QoL was compared with normality tables for the general Spanish population. Interactive effects were found in physical functioning (p = 0.008), role-physical (p = 0.016) and activity (p = 0.014). Diabetic patients reported worse scores when they were also obese and vice versa, that is, obese patients scored worse when they were also diabetic. Both diabetic and obese patients had lower QoL than those without metabolic pathology or the general population, and obese patients also reported more passive/avoidance coping. Active coping, positive reframing and acceptance predicted better QoL, while denial, self-blame, self-distraction, disengagement and religion predicted lower QoL. In conclusion, diabetes and obesity were associated with lower QoL in patients with NAFLD. Obesity was also associated with more passive/avoidance coping. Furthermore, passive/avoidance coping strategies predicted lower QoL than active, recommending modification of maladaptive coping strategies in future multidisciplinary NAFLD treatments. Full article
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Article
Utility of Liver Function Tests and Fatty Liver Index to Categorize Metabolic Phenotypes in a Mediterranean Population
Int. J. Environ. Res. Public Health 2020, 17(10), 3518; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph17103518 - 18 May 2020
Viewed by 804
Abstract
The aim of this study was to analyze the utility of liver function tests (LFT) and fatty liver index (FLI), a surrogate marker of non-alcoholic fatty liver disease, in the categorization of metabolic phenotypes in a Mediterranean population. A cross-sectional study was performed [...] Read more.
The aim of this study was to analyze the utility of liver function tests (LFT) and fatty liver index (FLI), a surrogate marker of non-alcoholic fatty liver disease, in the categorization of metabolic phenotypes in a Mediterranean population. A cross-sectional study was performed on a random representative sample of 2233 adults assigned to a health center in Málaga, Spain. The metabolic phenotypes were determined based on body mass index (BMI) categorization and the presence or absence of two or more cardiometabolic abnormalities (high blood pressure, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, pre-diabetes) or type 2 diabetes. No difference was observed between metabolically healthy and metabolically abnormal phenotypes on LFT. The mean FLI of the population was 41.1 ± 28.6. FLI was significantly higher (p < 0.001) in the metabolically abnormal phenotypes in all BMI categories. The proportion of individuals with pathological FLI (≥60) was significantly higher in the metabolically abnormal overweight and obese phenotypes (p < 0.001). On a multivariate model adjusted for sex, age, and waist circumference, a significant correlation was found between pathological FLI and metabolically abnormal phenotypes in the overweight and obese BMI categories. Area under the curve (AUC) of FLI as a biomarker was 0.76, 0.74, and 0.72 for the metabolically abnormal normal-weight, overweight, and obese groups, respectively. Liver biochemistry is poorly correlated with metabolic phenotypes. Conversely, a good correlation between FLI, as a marker of non-alcoholic fatty liver disease (NAFLD), and metabolically abnormal phenotypes in all BMI ranges was found. Our study suggests that FLI may be a useful marker for characterizing metabolically abnormal phenotypes in individuals who are overweight or obese. Full article
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Review

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Review
Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors
Int. J. Environ. Res. Public Health 2021, 18(10), 5227; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18105227 - 14 May 2021
Viewed by 766
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of chronic liver disease in the Western world, probably due to the growing prevalence of obesity, metabolic diseases, and exposure to some environmental agents. In certain patients, simple hepatic steatosis can [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of chronic liver disease in the Western world, probably due to the growing prevalence of obesity, metabolic diseases, and exposure to some environmental agents. In certain patients, simple hepatic steatosis can progress to non-alcoholic steatohepatitis (NASH), which can sometimes lead to liver cirrhosis and its complications including hepatocellular carcinoma. Understanding the mechanisms that cause the progression of NAFLD to NASH is crucial to be able to control the advancement of the disease. The main hypothesis considers that it is due to multiple factors that act together on genetically predisposed subjects to suffer from NAFLD including insulin resistance, nutritional factors, gut microbiota, and genetic and epigenetic factors. In this article, we will discuss the epidemiology of NAFLD, and we overview several topics that influence the development of the disease from simple steatosis to liver cirrhosis and its possible complications. Full article
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