Onset Of Non-alcoholic Fatty Liver Disease Research Articles

The Impact of Aerobic and Anaerobic Exercise Interventions on the Management and Outcomes of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder that includes non-alcoholic hepatic steatosis without or with moderate inflammation and non-alcoholic steatohepatitis (NASH), characterized by necroinflammation and a more rapid progression of fibrosis. It is the primary pathological basis for hepatocellular carcinoma. With its prevalence escalating annually, NAFLD has emerged as a global health epidemic, presenting a significant hazard to public health worldwide. Existing studies have shown that physical activity and exercise training have a positive effect on NAFLD. However, the extent to which exercise improves NAFLD depends on the type, intensity, and duration. Therefore, the type of exercise that has the best effect on improving NAFLD remains to be explored. To date, the most valuable discussions involve aerobic and anaerobic exercise. Exercise intervenes in the pathological process of NAFLD by regulating physiological changes in cells through multiple signaling pathways. The review aims to summarize the signaling pathways affected by two different exercise types associated with the onset and progression of NAFLD. It provides a new basis for improving and managing NAFLD in clinical practice.

Adipokine/hepatokines profiling of fatty liver in adolescents and young adults: cross-sectional and prospective analyses of the BCAMS study.

The underlying connections between obesity and non-alcoholic fatty liver disease (NAFLD) are not fully understood. One potential link might be the imbalanced adipokines and hepatokines. We aimed to explore the associations between specific adipokines/hepatokines and NAFLD in Chinese youth and to determine how these biomarkers mediate the obesity-NAFLD relationship. We analyzed data from the 10-year follow-up visit of the Beijing Children and Adolescents Metabolic Syndrome (BCAMS) study (n = 509; mean age = 20.2years) for a comprehensive metabolic risk assessment, including liver ultrasound and plasma measurements of adiponectin, leptin, fibroblast growth factor 21 (FGF21), retinol-binding protein 4 (RBP4), and angiopoietin-like protein 8 (ANGPTL8). Longitudinal analysis was performed on a subgroup (n = 307), with complete baseline (mean age = 12.2years) and follow-up data. Mediation models assessed how obesity at baseline and follow-up influence NAFLD through these biomarkers. Participants with NAFLD exhibited a high prevalence of central obesity (90.9%). Both cross-sectional and prospective analyses identified increased RBP4, FGF21, leptin, and decreased adiponectin levels as significant predictors of NAFLD. More adipokine/hepatokine abnormalities were linked to higher NAFLD risk. Furthermore, ratios reflecting adipokine/hepatokine imbalances, including leptin/adiponectin, FGF21/adiponectin, and RBP4/adiponectin, demonstrated stepwise changes correlating with NAFLD severity (all p < 0.05). Mediation analysis indicated that these four adipokines/hepatokines accounted for approximately 72.4% of the central obesity-NAFLD relationship and 80.1% in the subgroup analysis using baseline childhood data. Dysregulated adipokines/hepatokines may explain the onset or progression of obesity-related NAFLD in youths. Higher RBP4, FGF21 and leptin, alongside lower adiponectin, could serve as early biomarkers for NAFLD.

Caveolin-1 ameliorates hepatic injury in non-alcoholic fatty liver disease by inhibiting ferroptosis via the NOX4/ROS/GPX4 pathway

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally, with a complex and contentious pathogenesis. Caveolin-1 (CAV1) is an important regulator of liver function and can mitigate liver injury by scavenging reactive oxygen species (ROS). Evidence suggests that NOX4 is a source of ROS production, that oxidative stress and ferroptosis are closely related, and that both are involved in the onset and progression of NAFLD. However, whether CAV1 attenuates liver injury in NAFLD caused by high-fat diet via the NOX4/ROS/GPX4 pathway remains unclear. An in vivo fatty liver model was established by feeding mice with a high-fat diet for 16 weeks. In addition, an in vitro fatty liver model was established by incubating AML-12 cells with free fatty acids for 24 h using an in vitro culture method. In our study, it was observed that a high-fat diet induces mitochondrial damage and worsens oxidative stress in NAFLD. This diet also hinders GPX4 expression, leading to an escalation of ferroptosis and lipid accumulation. To counteract these effects, intraperitoneal administration of CSD peptide in mice attenuated the high-fat diet-induced liver mitochondrial damage and ferroptosis. Likewise, overexpression of CAV1 resulted in an increase in GPX4 expression and a reduction in levels of ROS-mediated iron metamorphosis, thus mitigating the progression of the disease. However, the effects of CAV1 on GPX4-mediated ferroptosis and lipid deposition could be reversed by CAV1 small interfering RNA (SiRNA). Finally, NOX4 inhibitor (GLX351322) treatment increased CAV1 siRNA-mediated GPX4 expression and decreased the level of ROS-mediated ferroptosis. These findings suggest a potential mechanism underlying the protective role of CAV1 against high-fat diet-induced hepatotoxicity in NAFLD, shedding new light on the interplay between CAV1, GPX4, and ferroptosis in liver pathology

Research on the function of epigenetic regulation in the inflammation of non-alcoholic fatty liver disease

Abstract Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition, characterized by a spectrum that progresses from simple hepatic steatosis to nonalcoholic steatohepatitis, which may eventually lead to cirrhosis and hepatocellular carcinoma. The precise pathogenic mechanisms underlying NAFLD and its related metabolic disturbances remain elusive. Epigenetic modifications, which entail stable transcriptional changes without altering the DNA sequence, are increasingly recognized as pivotal. The principal forms of epigenetic modifications include DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. These alterations participate in the regulation of hepatic lipid metabolism, insulin resistance, mitochondrial injury, oxidative stress response, and release of inflammatory cytokines, all of which are associated with the onset and progression of NAFLD. This review discussed recent advances in understanding the potential epigenetic regulation of inflammation in NAFLD. Unraveling these epigenetic mechanisms may facilitate the identification of early diagnostic biomarkers and the development of targeted therapeutic strategies for NAFLD.

Polyphenols improve non-alcoholic fatty liver disease via gut microbiota: A comprehensive review.

Polyphenols, natural micronutrients derived from plants, are valued for their anti-inflammatory and antioxidant properties. The escalating global prevalence of non-alcoholic fatty liver disease (NAFLD) underscores its status as a chronic progressive liver condition. Furthermore, the dysregulation of gut microbiota (GM) is implicated in the onset and progression of NAFLD through the actions of metabolites such as bile acids (BAs), lipopolysaccharide (LPS), choline, and short-chain fatty acids (SCFAs). Additionally, GM may influence the integrity of the intestinal barrier. This review aims to evaluate the potential effects of polyphenols on GM and intestinal barrier function, and their subsequent impact on NAFLD. We searched through a wide range of databases, such as Web of Science, PubMed, EMBASE, and Scopus to gather information for our non-systematic review of English literature. GM functions and composition can be regulated by polyphenols such as chlorogenic acid, curcumin, green tea catechins, naringenin, quercetin, resveratrol, and sulforaphane. Regulating GM composition improves NAFLD by alleviating inflammation, liver fat accumulation, and liver enzymes. Furthermore, it improves serum lipid profile and gut barrier integrity. All of these components affect NAFLD through the metabolites of GM, including SCFAs, choline, LPS, and BAs. Current evidence indicates that chlorogenic acid, resveratrol, quercetin, and curcumin can modulate GM, improving intestinal barrier integrity and positively impacting NAFLD. More studies are necessary to evaluate the safety and efficacy of naringenin, sulforaphane, and catechin.

Food Insecurity in Hispanic Populations Is Associated with an Increased Risk of Hepatic Steatosis: A Nationally Representative Study.

Introduction: The Hispanic population in the US faces a higher risk of nonalcoholic fatty liver disease (NAFLD). Multiple factors influence this risk, including genetics, environmental factors, and socioeconomic statuses. Inadequate access to nutritious foods, or food insecurity, is prevalent among Hispanic individuals and poses a metabolic risk for both the onset and development of NAFLD. Materials and Methods: We utilized the National Health and Nutrition Examination Survey (NHANES) 2017-2020 pre-pandemic data to analyze the association between Hispanic ethnicity, hepatic steatosis, fibrosis, and food insecurity. Vibration-controlled transient elastography (VCTE) was employed to assess liver stiffness (LSM) and controlled attenuation parameter (CAP) scores to determine fibrosis and steatosis, respectively. Linear and ordinal logistic regression models were applied to their continuous, log-transformed, and categorical forms, adjusting for demographics, metabolic comorbidities, and socioeconomic factors. Models were subsequently stratified based on food security statuses. Results: A total of 7396 Hispanic participants were included in the study. Under multivariable analysis, Hispanic individuals had higher CAP scores (Beta-coefficient: 10.2 dB/m, 95% CI: 6.1-14.4 dB/m, p = 0.001)) vs. non-Hispanic individuals, without statistically significant differences in fibrosis. Food-insecure participants exhibited higher CAP scores than their food-secure counterparts. After stratification, a stronger association between Hispanic ethnicity and CAP scores was evident in the food-insecure group (Beta-coefficient: 11.8 dB/m, 95% CI: 4.4-19.3 dB/m, p = 0.003). Discussion: This study demonstrates the heightened risk of hepatic steatosis among individuals with Hispanic ancestry in the US. The risk is exacerbated by food insecurity, particularly for Hispanic individuals. The contribution is linked to the dietary habits in this population that lead to metabolic risk factors associated with hepatic steatosis. Considering the rising prevalence of NAFLD and food insecurity, interventions focusing on nutritional support and healthcare access among this population could mitigate these burdens.

Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent pediatric liver disorder, primarily attributed to dietary shifts in recent years. NAFLD is characterized by the accumulation of lipid species in hepatocytes, leading to liver inflammation that can progress to steatohepatitis, fibrosis, and cirrhosis. Risk factors contributing to NAFLD encompass genetic variations and metabolic disorders such as obesity, diabetes, and insulin resistance. Moreover, transgenerational influences, resulting in an imbalance of gut microbial composition, epigenetic modifications, and dysregulated hepatic immune responses in offspring, play a pivotal role in pediatric NAFLD development. Maternal nutrition shapes the profile of microbiota-derived metabolites in offspring, exerting significant influence on immune system regulation and the development of metabolic syndrome in offspring. In this review, we summarize recent evidence elucidating the intricate interplay between gut microbiota, epigenetics, and immunity in fetuses exposed to maternal nutrition, and its impact on the onset of NAFLD in offspring. Furthermore, potential therapeutic strategies targeting this network are also discussed.

Supplementation of Micro- and Macronutrients-A Role of Nutritional Status in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a condition in which the pathological cumulation of fat with coexisting inflammation and damage of hepatic cells leads to progressive dysfunctions of the liver. Except for the commonly well-known major causes of NAFLD such as obesity, dyslipidemia, insulin resistance, or diabetes, an unbalanced diet and imbalanced nutritional status should also be taken into consideration. In this narrative review, we summarized the current knowledge regarding the micro- and macronutrient status of patients suffering from NAFLD considering various diets and supplementation of chosen supplements. We aimed to summarize the knowledge indicating which nutritional impairments may be associated with the onset and progression of NAFLD at the same time evaluating the potential therapy targets that could facilitate the healing process. Except for the above-mentioned objectives, one of the most important aspects of this review was to highlight the possible strategies for taking care of NAFLD patients taking into account the challenges and opportunities associated with the micronutrient status of the patients. The current research indicates that a supplementation of chosen vitamins (e.g., vitamin A, B complex, C, or D) as well as chosen elements such as zinc may alleviate the symptoms of NAFLD. However, there is still a lack of sufficient data regarding healthy ranges of dosages; thus, further research is of high importance in this matter.

Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.

Non-alcoholic fatty liver disease and sleep disorders.

Studies have shown that non-alcoholic fatty liver disease (NAFLD) may be associated with sleep disorders. In order to explore the explicit relationship between the two, we systematically reviewed the effects of sleep disorders, especially obstructive sleep apnea (OSA), on the incidence of NAFLD, and analyzed the possible mechanisms after adjusting for confounding factors. NAFLD is independently associated with sleep disorders. Different sleep disorders may be the cause of the onset and aggravation of NAFLD. An excessive or insufficient sleep duration, poor sleep quality, insomnia, sleep-wake disorders, and OSA may increase the incidence of NAFLD. Despite that some research suggests a unidirectional causal link between the two, specifically, the onset of NAFLD is identified as a result of changes in sleep characteristics, and the reverse relationship does not hold true. Nevertheless, there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD. Further research is needed to establish a clear relationship between NAFLD and sleep disorders. This will lay the groundwork for earlier identification of potential patients, which is crucial for earlier monitoring, diagnosis, effective prevention, and treatment of NAFLD.

Bacteroides and NAFLD: pathophysiology and therapy.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition observed globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Currently, the US Food and Drug Administration (FDA) has not approved any drugs for the treatment of NAFLD. NAFLD is characterized by histopathological abnormalities in the liver, such as lipid accumulation, steatosis, hepatic balloon degeneration, and inflammation. Dysbiosis of the gut microbiota and its metabolites significantly contribute to the initiation and advancement of NAFLD. Bacteroides, a potential probiotic, has shown strong potential in preventing the onset and progression of NAFLD. However, the precise mechanism by which Bacteroides treats NAFLD remains uncertain. In this review, we explore the current understanding of the role of Bacteroides and its metabolites in the treatment of NAFLD, focusing on their ability to reduce liver inflammation, mitigate hepatic steatosis, and enhance intestinal barrier function. Additionally, we summarize how Bacteroides alleviates pathological changes by restoring the metabolism, improving insulin resistance, regulating cytokines, and promoting tight-junctions. A deeper comprehension of the mechanisms through which Bacteroides is involved in the pathogenesis of NAFLD should aid the development of innovative drugs targeting NAFLD.

Circulating Bone morphogenetic protein 9(BMP9) as a new biomarker for noninvasive stratification of nonalcoholic fatty liver disease and metabolic syndrome.

Nonalcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome (MetS). Bone morphogenetic protein 9 (BMP9) is an essential factor in glucose, lipid and energy metabolism. This study aims to investigate whether BMP9 can serve as a serological marker for the severity of NAFLD or MetS. Blood samples, clinical data and FibroTouch test were collected from consecutively recruited 263 individuals in Shanghai East hospital. All the participants were divided into three groups: the healthy controls, nonalcoholic fatty liver (NAFL) group and nonalcoholic steatohepatitis (NASH) at-risk group according to the results of FibroTouch test and liver function. Serum BMP9 levels were measured by enzyme-linked immunosorbent assay. Serum BMP9 levels were positively correlated with transaminase, triglyceride, fasting plasma glucose, glycated hemoglobin (HbA1c) and uric acid while it showed a downward trend as the increasing number of MetS components. Furthermore, it differentiated NASH at-risk (58.13 ± 2.82ng/L) from the other groups: healthy control (70.32 ± 3.70ng/L) and NAFL (64.34 ± 4.76ng/L) (p < 0.0001). Controlled attenuation parameter of liver fat and liver stiffness measurement were negatively correlated with BMP9 levels, while high-density lipoprotein levels were positively correlated. The risk of developing NAFLD increased along with elevated serum BMP9 and BMI, and a significantly higher risk was observed in men compared to women. BMP9 should be considered a protective factor for the onset and development of NAFLD, as well as a promising biomarker for the severity of the NAFLD and MetS.

Research Progress on Lipophagy-Mediated Exercise Intervention in Non-Alcoholic Fatty Liver Disease.

Lipophagy is a cellular pathway targeting the lysosomal degradation of lipid droplets, playing a role in promoting lipid turnover and renewal. Abnormal lipophagy processes can lead to the occurrence and development of non-alcoholic fatty liver disease (NAFLD), characterized by the deposition of lipid droplets (LDs) in the liver. The importance of exercise training in preventing and improving NAFLD has been well-established, but the exact mechanisms remain unclear. Recent research findings suggest that lipophagy may serve as a crucial hub for liver lipid turnover under exercise conditions. Exercise may alleviate hepatic lipid accumulation and mitigate inflammatory responses and fibrosis through lipophagy, thereby improving the onset and progression of NAFLD.

Interleukins: Pathogenesis in Non-Alcoholic Fatty Liver Disease.

Inflammatory cytokines have been implicated as crucial contributors to the onset and progression of non-alcoholic fatty liver disease (NAFLD). The exact mechanisms by which interleukins (ILs) contribute to NAFLD may vary, and ongoing research is aimed at understanding the specific roles of different ILs in the pathogenesis of this condition. In addition, variations in environmental factors and genetics in each individual can influence the onset and/or progression of NAFLD. The lack of clinical studies related to the potential therapeutic properties of IL-1 inhibitors currently does not allow us to conclude their validity as a therapeutic option, although preclinical studies show promising results. Further studies are needed to elucidate their beneficial properties in NAFLD treatment.

Impact of gut microbiota on nonalcoholic fatty liver disease: insights from a leave-one-out cross-validation study.

Enteric dysbacteriosis is strongly associated with nonalcoholic fatty liver disease (NAFLD). However, the underlying causal relationship remains unknown. Thus, the present study aimed to investigate the relationship between gut microbiota and NAFLD using Mendelian randomization (MR) and analyze the target genes potentially regulated by specific microbiota. Bidirectional two-sample MR analysis was performed using inverse variance weighted (IVW) supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Data were pooled from gut microbiota and NAFLD association studies. The least absolute shrinkage, selection operator regression, and the Support Vector Machine algorithm were used to identify genes regulated by these intestinal flora in NAFLD. The liver expression of these genes was verified in methionine choline-deficient (MCD) diet-fed mice. IVW results confirmed a causal relationship between eight specific gut microbes and NAFLD. Notably, the order Actinomycetales, NB1n, the family Actinomycetaceae, Oxalobacteraceae and the genus Ruminococcaceae UCG005 were positively correlated, whereas Lactobacillaceae, the Christensenellaceae R7 group, and Intestinibacter were negatively correlated with NAFLD onset. In NAFLD, these eight bacteria regulated four genes: colony-stimulating factor 2 receptor β, fucosyltransferase 2, 17-beta-hydroxysteroid dehydrogenase 14, and microtubule affinity regulatory kinase 3 (MAPK3). All genes, except MARK3, were differentially expressed in the liver tissues of MCD diet-fed mice. The abundance of eight gut microbiota species and NAFLD progression displayed a causal relationship based on the expression of the four target genes. Our findings contributed to the advancement of intestinal microecology-based diagnostic technologies and targeted therapies for NAFLD.

The Correlation Between Serum Copper and Non-alcoholic Fatty Liver Disease in American Adults: an Analysis Based on NHANES 2011 to 2016.

Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal-Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 μmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38-3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17-5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m2) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations.

Association between sleep duration and a new onset of nonalcoholic fatty liver disease.

Objective A short sleep duration is associated with non-alcoholic fatty liver disease (NAFLD). However, the causal relationship between a short sleep duration and the onset of NAFLD remains unknown because of the lack of any longitudinal studies. Therefore, we evaluated the association between sleep duration and the onset of NAFLD. Methods We evaluated health checkup data for 1,862 NAFLD-free Japanese adults aged 33-86 years at baseline and followed those individuals for a median of 41 months. Hepatic steatosis was examined using ultrasonography (US). The Cox proportional hazards model was used to evaluate the association between sleep duration and NAFLD onset. Results Among the 1,862 participants, 483 (25.9%) developed NAFLD. The proportion of women who developed NAFLD was the highest in the group with a sleep duration of <6 hours and lowest in the group with a sleep duration of 7 to <8 hours. The multivariable-adjusted hazard ratio (95% confidence interval) for the onset of NAFLD in women with a sleep duration <6 hours compared with those with a sleep duration of 7 to <8 hours was 1.55 (1.09-2.20; p=0.02). Conclusions In women, a short sleep duration was independently associated with the onset of NAFLD, thus suggesting that an adequate sleep duration can be a promising preventive factor for the onset of NAFLD in women.

A bibliometric analysis of macrophages associated with non-alcoholic fatty liver disease research from 2005 to 2023

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition associated with the risk of progressing to decompensated cirrhosis and hepatocellular carcinoma. While macrophages play a crucial role in the development of NAFLD, their heterogeneity and plasticity allow them to undertake diverse roles in immune response, tissue repair, and maintaining tissue homeostasis. Thus, the exact involvement of macrophages in the onset and progression of NAFLD remains to be further explored. This study aims to employ bibliometric analysis to elucidate the role of macrophages in the pathogenesis of NAFLD, analyze research focal points in this domain, and speculate on future research trends. The literature search, conducted using the Web of Science Core Collection, encompassed articles and reviews related to macrophages and NAFLD published between 2005 and 2023. A bibliometric analysis of 1264 extracted publications was performed using VOSviewer 1.6.17 and Citespace 6.1. R2, evaluating parameters such as spatial and temporal distribution, authors, thematic categories, topic distribution, references, and keywords. The findings revealed a steady global increase in publications in this field, with the United States contributing the most followed by China. The University of California System produced the highest volume of publications, while the Journal of Hepatology had the highest impact factors among the top 10 publishing journals. Tacke Frank emerged as both the most prolific author and the most cited. Co-occurrence and burst analysis of keywords and references highlighted the hotspots in this research area, emphasizing the mechanisms of NAFLD pathogenesis, metabolic regulation, immune modulation, and oxidative stress. Maintaining hepatic homeostasis by liver macrophages and macrophage polarization were identified as trending research directions in this field. Based on the bibliometric analysis, continued attention toward NAFLD therapeutic research involving hepatic macrophages is anticipated. As the mechanisms underlying NAFLD pathogenesis are further elucidated, the development of more treatment approaches related to macrophage immunology and metabolic regulation may expand therapeutic options. This study offers valuable insights into the current state and future trends in the field, providing beneficial guidance to researchers aiming to make significant contributions.

Lifestyle factors affecting new-onset nonalcoholic fatty liver disease

Evidence for the influence of lifestyle factors on nonalcoholic fatty liver disease (NAFLD) onset is limited because the association between lifestyle factors and NAFLD has been reported mostly in cross-sectional studies. Our purpose was to elucidate which lifestyle factors are associated with NAFLD onset by performing a longitudinal study. This was a longitudinal study of 1,713 Japanese participants who underwent multiple health checkups from June 2013 to the end of March 2018 and were not diagnosed with NAFLD at the first health checkup at Watari Hospital in Fukushima, Japan. Baseline characteristics, including lifestyle factors, were compared among participants with and without NAFLD. Cox proportional hazards models were used to identify the association between lifestyle factors and NAFLD onset. Among the 1,713 participants, 420 (24.5 %) developed NAFLD during the observation period (median 47 months). There were significant differences in body mass index and hepatobiliary enzyme levels between participants with and without NAFLD. In Cox proportional hazards models, eating between meals (hazard ratio (HR): 2.08, 95 % confidence interval (CI): 1.25–3.45, p < 0.01) and eating fast (HR: 1.59, 95 % CI: 1.26–2.00, p < 0.01) were risk factors for NAFLD onset in men and women, respectively. Moreover, fast walking was a protective factor against NAFLD onset in women (HR: 0.76, 95 % CI: 0.60–0.96, p = 0.02). These findings could help to identify patients at risk and prevent future NAFLD onset.

Impact of smoking cessation on non-alcoholic fatty liver disease prevalence: a systematic review and meta-analysis

ObjectivesThe negative effects of smoking on numerous cardiovascular and metabolic diseases have been widely acknowledged. However, the potential effect of smoking cessation is relatively unelucidated. The objective of this study...