10th Anniversary of Biomedicines—NAFLD: From Mechanisms to Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 21857

Special Issue Editors


E-Mail Website
Guest Editor
1. Service of Endocrinology, Diabetes, Hypertension and Nutrition, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland
2. Diabetes Center, Geneva University, Rue Michel-Servet 1, 1206 Genève, Switzerland
Interests: NAFLD; NASH; insulin resistance; type 2 diabetes; metabolic syndrome; endocrine diseases
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
1. Service of Endocrinology, Diabetes, Hypertension and Nutrition, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland
2. Diabetes Center, Geneva University, Rue Michel-Servet 1, 1206 Genève, Switzerland
Interests: NAFLD; NASH; type 2 diabetes; diabetic foot infection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The year 2023 marks the 10th anniversary of Biomedicines, a peer-reviewed open access journal in the biomedical field. So far, Biomedicines has published more than 2700 papers from more than 17,000 authors. We appreciate each author, reviewer, and academic editor whose support has brought us to where we are today.

To celebrate this significant milestone, we aim to publish a Special Issue entitled 10th Anniversary of Biomedicines—NAFLD: From Mechanisms to Therapeutic Approaches.

NAFLD is the most common cause of chronic liver disease worldwide today, affecting approximately 30% of the general population, and its prevalence continues to increase notably due to the growing obesity epidemic. Therefore, NAFLD is projected to soon become the most common indication leading to liver transplantation in the United States. Moreover, the prevalence of NAFLD can reach 90–95% in obese individuals and affects up to 70% of patients with type 2 diabetes. The estimation of NASH prevalence is more difficult to accurately determine because diagnosis requires a liver biopsy, which is infrequently performed. However, hepatic fibrosis is the only histologic feature of NASH independently associated with long-term overall mortality, liver transplantation, and liver-related mortality. Therefore, it is of crucial importance to better understand the mechanisms leading to the development of NAFLD/NASH and notably fibrosis in order to find therapeutic targets to prevent fibrosis initiation or reverse this process.

We hope that this Special Issue will provide interesting insights into the pathophysiological mechanisms leading to NAFLD/NASH and explore potential therapeutic targets that could be promising over the coming years in the prevalent liver disease.

Dr. François R. Jornayvaz
Dr. Karim Gariani
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • NAFLD
  • NASH
  • insulin resistance
  • type 2 diabetes
  • obesity
  • pathophysiological mechanisms
  • therapeutic targets
  • inflammation
  • gut microbiota
  • fibrosis
  • endocrine diseases

Related Special Issue

Published Papers (12 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

11 pages, 827 KiB  
Article
Insulin Resistance Is the Main Characteristic of Metabolically Unhealthy Obesity (MUO) Associated with NASH in Patients Undergoing Bariatric Surgery
by Sophia M. Schmitz, Sebastian Storms, Alexander Koch, Christine Stier, Andreas Kroh, Karl P. Rheinwalt, Sandra Schipper, Karim Hamesch, Tom F. Ulmer, Ulf P. Neumann and Patrick H. Alizai
Biomedicines 2023, 11(6), 1595; https://doi.org/10.3390/biomedicines11061595 - 31 May 2023
Cited by 2 | Viewed by 1158
Abstract
(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be [...] Read more.
(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m2 (36–74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ2 (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ2 (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease. Full article
Show Figures

Figure 1

13 pages, 2907 KiB  
Article
Do Semaphorins Play a Role in Development of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease?
by Lara Šamadan, Neven Papić, Maja Mijić, Ivana Knežević Štromar, Slavko Gašparov and Adriana Vince
Biomedicines 2022, 10(12), 3014; https://doi.org/10.3390/biomedicines10123014 - 23 Nov 2022
Cited by 1 | Viewed by 1476
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with systemic changes in immune response linked with chronic low-grade inflammation and disease progression. Semaphorins, a large family of biological response modifiers, were recently recognized as one of the key regulators of immune responses, possibly also [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is associated with systemic changes in immune response linked with chronic low-grade inflammation and disease progression. Semaphorins, a large family of biological response modifiers, were recently recognized as one of the key regulators of immune responses, possibly also associated with chronic liver diseases. The aim of this study was to identify semaphorins associated with NAFLD and their relationship with steatosis and fibrosis stages. In this prospective, case-control study, serum semaphorin concentrations (SEMA3A, -3C, -4A, -4D, -5A and -7A) were measured in 95 NAFLD patients and 35 healthy controls. Significantly higher concentrations of SEMA3A, -3C and -4D and lower concentrations of SEAMA5A and -7A were found in NAFLD. While there was no difference according to steatosis grades, SEMA3C and SEMA4D significantly increased and SEMA3A significantly decreased with fibrosis stages and had better accuracy in predicting fibrosis compared to the FIB-4 score. Immunohistochemistry confirmed higher expression of SEMA4D in hepatocytes, endothelial cells and lymphocytes in NAFLD livers. The SEMA5A rs1319222 TT genotype was more frequent in the NAFLD group and was associated with higher liver stiffness measurements. In conclusion, we provide the first evidence of the association of semaphorins with fibrosis in patients with NAFLD. Full article
Show Figures

Figure 1

14 pages, 2313 KiB  
Article
Identification of a Fatty Acid for Diagnosing Non-Alcoholic Steatohepatitis in Patients with Severe Obesity Undergoing Metabolic Surgery
by Naoto Takahashi, Akira Sasaki, Akira Umemura, Tamotsu Sugai, Keisuke Kakisaka and Yasushi Ishigaki
Biomedicines 2022, 10(11), 2920; https://doi.org/10.3390/biomedicines10112920 - 14 Nov 2022
Cited by 2 | Viewed by 1206
Abstract
The prevalence of nonalcoholic steatohepatitis (NASH) in severely obese Japanese patients is extremely high. However, there are currently no methods other than liver biopsy to assess hepatic steatosis and fibrosis. The purpose of this study was to comprehensively analyze changes in fatty acid [...] Read more.
The prevalence of nonalcoholic steatohepatitis (NASH) in severely obese Japanese patients is extremely high. However, there are currently no methods other than liver biopsy to assess hepatic steatosis and fibrosis. The purpose of this study was to comprehensively analyze changes in fatty acid (FA) and serum-free fatty acid (FFA) metabolism in severely obese Japanese patients to determine whether these could be surrogate markers. In this study, we enrolled 20 Japanese patients who underwent laparoscopic sleeve gastrectomy (LSG) for severe obesity and intraoperative liver biopsy. Serum FFAs were analyzed with liquid chromatography-mass spectrometry, and FAs in liver tissue were assessed using matrix-assisted laser desorption/ionization-imaging mass spectrometry to determine FAs that may be indicative of a positive NASH diagnosis. All patients showed significant weight loss and metabolic improvement following LSG. Regarding weight loss and metabolic improvement indices, 23 FFAs showed significant correlations with the baseline data. Narrowing down the phospholipids to commonly detected FAs detected in liver tissue, PC(18:1e_20:4) was significantly changed in the NASH group, suggesting that it could be used as a surrogate marker for NASH diagnosis. The results suggest that specific postoperative changes in blood phospholipids could be used as surrogate markers for NASH treatment. Full article
Show Figures

Figure 1

12 pages, 988 KiB  
Article
The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus
by Chia-Yen Dai, Tzu-Jung Fang, Wei-Wen Hung, Hui-Ju Tsai and Yi-Chun Tsai
Biomedicines 2022, 10(7), 1487; https://doi.org/10.3390/biomedicines10071487 - 23 Jun 2022
Cited by 9 | Viewed by 1983
Abstract
Liver fibrosis is a key pathophysiology process in chronic liver disease. It is still unclear whether the impact of liver fibrosis is not fully realized in type 2 diabetes mellitus (T2D) patients with nonalcoholic fatty liver disease (NAFLD), and the factors affecting nonalcoholic [...] Read more.
Liver fibrosis is a key pathophysiology process in chronic liver disease. It is still unclear whether the impact of liver fibrosis is not fully realized in type 2 diabetes mellitus (T2D) patients with nonalcoholic fatty liver disease (NAFLD), and the factors affecting nonalcoholic steatohepatitis (NASH) or liver stiffness also remain unclear. The aim of this study was to evaluate the determinants of liver fibrosis and in T2D patients with NAFLD. Liver fibrosis and steatosis were measured using transient elastography (FibroScan). Of 226 T2D patients with NAFLD, 50 with liver fibrosis had higher body mass index, serum uric acid, triglyceride and glycated hemoglobin levels and lower high density lipoprotein levels than 176 without liver fibrosis. Multivariate analysis revealed that aging, obesity, sulfonylurea usage and high levels of AST increased the risk of liver fibrosis in T2D patients with NAFLD. Our findings provide useful information to clinical physicians for earlier detection of liver fibrosis in T2D patients with NAFLD and to prevent liver fibrosis through controlling these risk factors. Full article
Show Figures

Figure 1

Review

Jump to: Research, Other

15 pages, 1454 KiB  
Review
Gene Variants Implicated in Steatotic Liver Disease: Opportunities for Diagnostics and Therapeutics
by Gary Huang, Daniel F. Wallace, Elizabeth E. Powell, Tony Rahman, Paul J. Clark and V. Nathan Subramaniam
Biomedicines 2023, 11(10), 2809; https://doi.org/10.3390/biomedicines11102809 - 17 Oct 2023
Cited by 4 | Viewed by 1190
Abstract
Non-alcoholic fatty liver disease (NAFLD) describes a steatotic (or fatty) liver occurring as a consequence of a combination of metabolic, environmental, and genetic factors, in the absence of significant alcohol consumption and other liver diseases. NAFLD is a spectrum of conditions. Steatosis in [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) describes a steatotic (or fatty) liver occurring as a consequence of a combination of metabolic, environmental, and genetic factors, in the absence of significant alcohol consumption and other liver diseases. NAFLD is a spectrum of conditions. Steatosis in the absence of inflammation is relatively benign, but the disease can progress into more severe forms like non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. NAFLD onset and progression are complex, as it is affected by many risk factors. The interaction between genetic predisposition and other factors partially explains the large variability of NAFLD phenotype and natural history. Numerous genes and variants have been identified through large-scale genome-wide association studies (GWAS) that are associated with NAFLD and one or more subtypes of the disease. Among them, the largest effect size and most consistent association have been patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane-bound O-acyltransferase domain containing 7 (MBOAT7) genes. Extensive in vitro and in vivo studies have been conducted on these variants to validate these associations. The focus of this review is to highlight the genetics underpinning the molecular mechanisms driving the onset and progression of NAFLD and how they could potentially be used to improve genetic-based diagnostic testing of the disease and develop personalized, targeted therapeutics. Full article
Show Figures

Figure 1

12 pages, 2067 KiB  
Review
Extracellular Vesicles as Therapeutic and Diagnostic Tools for Chronic Liver Diseases
by Aleksandra Leszczynska, Christian Stoess, Hana Sung, Davide Povero, Akiko Eguchi and Ariel Feldstein
Biomedicines 2023, 11(10), 2808; https://doi.org/10.3390/biomedicines11102808 - 17 Oct 2023
Viewed by 1136
Abstract
Chronic liver diseases can lead to fibrotic changes that may progress to the development of cirrhosis, which poses a significant risk for morbidity and increased mortality rates. Metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and viral hepatitis are prevalent liver [...] Read more.
Chronic liver diseases can lead to fibrotic changes that may progress to the development of cirrhosis, which poses a significant risk for morbidity and increased mortality rates. Metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and viral hepatitis are prevalent liver diseases that may lead to cirrhosis. The advanced stages of cirrhosis can be further complicated by cancer development or end-stage liver disease and liver failure. Hence, early detection and diagnosis of liver fibrosis is crucial for preventing the progression to cirrhosis and improving patient outcomes. Traditionally, invasive liver biopsy has been considered the gold standard for diagnosing and staging liver fibrosis. In the last decade, research has focused on non-invasive methods, known as liquid biopsies, which involve the identification of disease-specific biomarkers in human fluids, such as blood. Among these alternative approaches, extracellular vesicles (EVs) have emerged as promising diagnostic and therapeutic tools for various diseases, including chronic liver diseases. EVs are released from stressed or damaged cells and can be isolated and quantified. Moreover, EVs facilitate cell-to-cell communication by transporting various cargo, and they have shown the potential to reduce the expression of profibrogenic markers, making them appealing tools for novel anti-fibrotic treatments. This review focuses on the impact of EVs in chronic liver diseases and exploring their potential applications in innovative therapeutic and diagnostic approaches. Full article
Show Figures

Figure 1

19 pages, 1104 KiB  
Review
Steatotic Liver Disease: Metabolic Dysfunction, Alcohol, or Both?
by Katharina Staufer and Rudolf E. Stauber
Biomedicines 2023, 11(8), 2108; https://doi.org/10.3390/biomedicines11082108 - 26 Jul 2023
Cited by 7 | Viewed by 1830
Abstract
Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), both of them accounting for fatty liver disease (FLD), are among the most common chronic liver diseases globally, contributing to substantial public health burden. Both NAFLD and ALD share a similar picture of [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), both of them accounting for fatty liver disease (FLD), are among the most common chronic liver diseases globally, contributing to substantial public health burden. Both NAFLD and ALD share a similar picture of clinical presentation yet may have differences in prognosis and treatment, which renders early and accurate diagnosis difficult but necessary. While NAFLD is the fastest increasing chronic liver disease, the prevalence of ALD has seemingly remained stable in recent years. Lately, the term steatotic liver disease (SLD) has been introduced, replacing FLD to reduce stigma. SLD represents an overarching term to primarily comprise metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as alcohol-related liver disease (ALD), and MetALD, defined as a continuum across which the contribution of MASLD and ALD varies. The present review discusses current knowledge on common denominators of NAFLD/MASLD and ALD in order to highlight clinical and research needs to improve our understanding of SLD. Full article
Show Figures

Figure 1

17 pages, 338 KiB  
Review
Experimental Data on the Role of Melatonin in the Pathogenesis of Nonalcoholic Fatty Liver Disease
by Dimitar Terziev and Dora Terzieva
Biomedicines 2023, 11(6), 1722; https://doi.org/10.3390/biomedicines11061722 - 15 Jun 2023
Cited by 2 | Viewed by 1896
Abstract
Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide, its complex pathogenesis remains incompletely understood. The currently stated hypotheses cannot fully clarify the interrelationships between individual pathogenetic mechanisms of the disease. No appropriate health strategies have been developed for treating NAFLD. [...] Read more.
Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide, its complex pathogenesis remains incompletely understood. The currently stated hypotheses cannot fully clarify the interrelationships between individual pathogenetic mechanisms of the disease. No appropriate health strategies have been developed for treating NAFLD. NAFLD is characterized by an accumulation of triglycerides in hepatic cells (steatosis), with the advanced form known as nonalcoholic steatohepatitis. In the latter, superimposed inflammation can lead to fibrosis. There are scientific data on NAFLD’s association with components of metabolic syndrome. Hormonal factors are thought to play a role in the development of metabolic syndrome. Endogenous melatonin, an indoleamine hormone synthesized by the pineal gland mainly at night, is a powerful chronobiotic that probably regulates metabolic processes and has antioxidant, anti-inflammatory, and genomic effects. Extrapineal melatonin has been found in various tissues and organs, including the liver, pancreas, and gastrointestinal tract, where it likely maintains cellular homeostasis. Melatonin exerts its effects on NAFLD at the cellular, subcellular, and molecular levels, affecting numerous signaling pathways. In this review article, we discuss the experimental scientific data accumulated on the involvement of melatonin in the intimate processes of the pathogenesis of NAFLD. Full article
19 pages, 683 KiB  
Review
Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies
by Erica Vetrano, Luca Rinaldi, Andrea Mormone, Chiara Giorgione, Raffaele Galiero, Alfredo Caturano, Riccardo Nevola, Raffaele Marfella and Ferdinando Carlo Sasso
Biomedicines 2023, 11(2), 468; https://doi.org/10.3390/biomedicines11020468 - 06 Feb 2023
Cited by 17 | Viewed by 3365
Abstract
In recent years, the incidence of non-viral hepatocellular carcinoma (HCC) has increased dramatically, which is probably related to the increased prevalence of metabolic syndrome, together with obesity and type 2 diabetes mellitus (T2DM). Several epidemiological studies have established the association between T2DM and [...] Read more.
In recent years, the incidence of non-viral hepatocellular carcinoma (HCC) has increased dramatically, which is probably related to the increased prevalence of metabolic syndrome, together with obesity and type 2 diabetes mellitus (T2DM). Several epidemiological studies have established the association between T2DM and the incidence of HCC and have demonstrated the role of diabetes mellitus as an independent risk factor for the development of HCC. The pathophysiological mechanisms underlying the development of Non-alcoholic fatty liver disease (NAFLD) and its progression to Non-alcoholic steatohepatitis (NASH) and cirrhosis are various and involve pro-inflammatory agents, oxidative stress, apoptosis, adipokines, JNK-1 activation, increased IGF-1 activity, immunomodulation, and alteration of the gut microbiota. Moreover, these mechanisms are thought to play a significant role in the development of NAFLD-related hepatocellular carcinoma. Early diagnosis and the timely correction of risk factors are essential to prevent the onset of liver fibrosis and HCC. The purpose of this review is to summarize the current evidence on the association among obesity, NASH/NAFLD, T2DM, and HCC, with an emphasis on clinical impact. In addition, we will examine the main mechanisms underlying this complex relationship, and the promising strategies that have recently emerged for these diseases’ treatments. Full article
Show Figures

Figure 1

18 pages, 1662 KiB  
Review
PPARα in the Epigenetic Driver Seat of NAFLD: New Therapeutic Opportunities for Epigenetic Drugs?
by Claudia Theys, Dorien Lauwers, Claudina Perez-Novo and Wim Vanden Berghe
Biomedicines 2022, 10(12), 3041; https://doi.org/10.3390/biomedicines10123041 - 25 Nov 2022
Cited by 5 | Viewed by 1972
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic and the most common cause of chronic liver disease worldwide. It consists of a spectrum of liver disorders ranging from simple steatosis to NASH which predisposes patients to further fibrosis, cirrhosis and even hepatocarcinoma. [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic and the most common cause of chronic liver disease worldwide. It consists of a spectrum of liver disorders ranging from simple steatosis to NASH which predisposes patients to further fibrosis, cirrhosis and even hepatocarcinoma. Despite much research, an approved treatment is still lacking. Finding new therapeutic targets has therefore been a main priority. Known as a main regulator of the lipid metabolism and highly expressed in the liver, the nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) has been identified as an attractive therapeutic target. Since its expression is silenced by DNA hypermethylation in NAFLD patients, many research strategies have aimed to restore the expression of PPARα and its target genes involved in lipid metabolism. Although previously tested PPARα agonists did not ameliorate the disease, current research has shown that PPARα also interacts and regulates epigenetic DNMT1, JMJD3, TET and SIRT1 enzymes. Moreover, there is a growing body of evidence suggesting the orchestrating role of epigenetics in the development and progression of NAFLD. Therefore, current therapeutic strategies are shifting more towards epigenetic drugs. This review provides a concise overview of the epigenetic regulation of NAFLD with a focus on PPARα regulation and highlights recently identified epigenetic interaction partners of PPARα. Full article
Show Figures

Figure 1

Other

Jump to: Research, Review

11 pages, 2672 KiB  
Systematic Review
Systematic Review and Meta-Analysis of the Usefulness of Epicardial Fat Thickness as a Non-Invasive Marker of the Presence and Severity of Nonalcoholic Fatty Liver Disease
by Lorenzo A. Orci, François R. Jornayvaz, Christian Toso and Karim Gariani
Biomedicines 2022, 10(9), 2204; https://doi.org/10.3390/biomedicines10092204 - 06 Sep 2022
Cited by 3 | Viewed by 1559
Abstract
We performed a systematic review and meta-analysis to assess the association between epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD). This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) and was based [...] Read more.
We performed a systematic review and meta-analysis to assess the association between epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD). This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) and was based on a registered protocol (CRD 4201809 5493). We searched Medline and Embase until December 2021 for studies reporting on the association between EFT and NAFLD. Qualitative reviews, meta-analyses and meta-regressions were performed to explore this association. Effect sizes are reported as standardized mean differences. We included 12 studies, comprising 3610 individuals. EFT was evaluated with trans-thoracic echocardiography in nine studies, two studies using cardiac computed tomography and one study using magnetic resonance imaging (MRI). The presence of NAFLD was evaluated using transabdominal liver ultrasound in nine studies. Other studies used histology, magnetic resonance spectroscopy and MRI-derived proton density fat fraction. Liver biopsy was performed to assess the severity of NAFLD in four studies. The random-effects meta-analysis indicated that, as compared to control patients with lean livers, patients with NAFLD displayed significantly higher EFT (standardized mean difference 0.61, 95% confidence interval: 0.47–0.75, p < 0.0001, I2 = 72%). EFT was further significantly higher in patients with severe liver steatosis versus patients with mild–moderate liver steatosis (standardized mean difference 1.21 95% confidence interval: 0.26–2.16, p < 0.001, I2 S = 96%). Through the meta-regression analysis, we found that patients with increasingly higher blood levels of aspartate aminotransferase displayed an increasingly higher depth of association. The current meta-analysis suggests that EFT may represent a useful surrogate for assessing the presence and severity of NAFLD in a non-invasive manner. Full article
Show Figures

Figure 1

12 pages, 2771 KiB  
Systematic Review
Atherogenic Index of Plasma in Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis
by Abdulrahman Ismaiel, Oana Sabina Ciobanu, Mohamed Ismaiel, Daniel-Corneliu Leucuta, Stefan-Lucian Popa, Liliana David, Dilara Ensar, Nahlah Al Srouji and Dan L. Dumitrascu
Biomedicines 2022, 10(9), 2101; https://doi.org/10.3390/biomedicines10092101 - 27 Aug 2022
Cited by 5 | Viewed by 2155
Abstract
(1) Background: Approximately a billion people worldwide are affected by NAFLD, which places a high clinical burden and financial cost on society. Liver biopsy is the gold standard for diagnosing NAFLD, but its invasivity limits the early diagnosis of NAFLD. Hence, it is [...] Read more.
(1) Background: Approximately a billion people worldwide are affected by NAFLD, which places a high clinical burden and financial cost on society. Liver biopsy is the gold standard for diagnosing NAFLD, but its invasivity limits the early diagnosis of NAFLD. Hence, it is important to look for alternate techniques in detecting and diagnosing NAFLD. NAFLD is associated with atherosclerosis. The purpose of this study was to assess the effectiveness of the atherogenic index of plasma (AIP) as a non-invasive modality for predicting NAFLD. (2) Methods: A search using electronic databases PubMed, EMBASE, and Scopus was carried out to find observational studies, looking at research that had been published up until the date of 11 May 2022. The included studies’ quality, risk of bias, and internal validity were evaluated using the QUADAS-2 quality assessment tool. The key summary outcomes were the mean difference (MD) and area under the curve (AUC). (3) Results: A total of eight studies (81,178 participants) were included in our review, while 17% of the included participants had NAFLD. A sex distribution of 57.8% men and 42.2% women was observed. The AIP between NAFLD and the controls was not significant (MD 0.212 [95% CI 0.231–0.655]). A significant MD in AIP between the males and females with NAFLD was observed (MD 0.246 [95% CI 0.098–0.395]). The AIP predicted NAFLD with an AUC of 0.764 as well as in males (AUC 0.761) and females (AUC 0.733). (4) Conclusions: There was a substantial MD in the AIP between both sexes, but there was no significant difference in the AIP values between patients with NAFLD and the controls. The AIP is a reliable biomarker for the diagnosis of NAFLD since its ability to predict the development of NAFLD was comparable to that of the other biomarkers. Full article
Show Figures

Figure 1

Back to TopTop