Mild Nonalcoholic Fatty Liver Disease Research Articles

Leisure-Time Physical Activity, Time Spent Sitting and Risk of Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study in Puglia.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. The increasingly sedentary lifestyle in recent years may have accelerated the development of NAFLD, independent of the level of physical activity. The purpose of this cross-sectional study was to determine the association between leisure-time physical activity (LTPA) and time spent sitting (TSS) and the likelihood of developing NAFLD in a sample of men and women aged 18-64 years, from southern Italy. The study is based on two cohort studies, a randomized clinical trial and an observational cost-benefit study. A total of 1269 participants (51.5% women) drawn from 3992 eligible subjects were enrolled in this study. Leisure-time physical activity (LTPA) and time spent sitting (TSS) were assessed using the Italian long form of the International Physical Activity Questionnaire (IPAQ-LF), designed for administration to adults aged 18 to 65 years. The association of exposures with the probability of belonging to a certain NAFLD degree of severity. The probability of having mild, moderate, and severe NAFLD tends to decrease with increasing LTPA and decreasing TSS levels. We selected a combination of participants aged 50 years and older stratified by gender. Men had a statistically significant difference in the probability of developing moderate NAFLD if they spent 70 h per week sitting and had low LTPA, while among women there was a statistically significant difference in the probability of developing mild or moderate NAFLD if they had moderate LPTA and spent 35-70 h/week sitting. The study thus showed that the amount of LTPA and the amount of TSS are associated with development and progression of NAFLD, but this relationship is not a linear one-especially in women aged ≥ 50 years old.

Association between severity of nonalcoholic fatty liver disease and major adverse cardiovascular events in patients assessed by coronary computed tomography angiography

BackgroundThe effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear.MethodsA total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan–Meier analysis were used to assess poor prognosis.ResultsDuring the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54–5.66]; p = 0.001) and CAD-RADS categories 3–5 (HR = 16.31[6.34–41.92]; p < 0.001) were independent risk factors for MACEs. The Kaplan–Meier analysis showed that moderate to severe NAFLD patients had a worsen prognosis than mild NAFLD patients (log-rank p < 0.001). Moreover, the combined receiver operating characteristic curve of the severity of NAFLD and CAD-RADS category showed a good predicting performance for the risk of MACEs, with an area under the curve of 0.849 (95% CI = 0.786–0.911).ConclusionThe severity of NAFLD was independent risk factor for MACEs in patients with obstructive CAD, having CAD-RADS 3–5 categories on CCTA.

Relation between non-alcoholic fatty liver disease and carotid artery intimal media thickness as a surrogate for atherosclerosis: a systematic review and meta-analysis.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis. Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups. No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups. This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.

Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study

ObjectiveTo investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM).DesignNationwide population based study.SettingLongitudinal cohort study...

Comparison of size of the liver between patients with non-alcoholic fatty liver disease and healthy controls.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease across all age groups. Limited studies have been conducted to consider the relationship between NAFLD and liver size. This study aimed to compare the size of the liver between NAFLD patients and healthy controls. This case-control study was conducted on NAFLD patients (n = 300), and healthy subjects (n = 300) referred to the Golestan Hospital of Ahvaz from April to August 2021. All individuals underwent ultrasonography examination, and liver size was measured in the midclavicular line. Fatty liver was divided into three grades, I (mild), II (moderate), and III (severe), according to the disease severity. Anthropometric parameters, including age, sex, weight, height, and body mass index (BMI), were recorded. Finally, the size of the liver and its relationship with NAFLD and anthropometric parameters was evaluated. Patients had significantly higher weight, and BMI mean values than controls (P < 0.001). In comparison to controls, NAFLD patients had considerably larger livers on average. (149.05 ± 12.60 mm vs. 134.51 ± 12.09; P < 0.001). There was a significant tendency for larger liver size in normal to severe fatty liver patients (P < 0.001). In patients with mild, moderate, and severe NAFLD, the mean liver size was 144.34 ± 11.35, 154.21 ± 10.84, and 158.63 ± 13.45 mm, respectively. The mean liver size in both groups was significantly higher in males than females (P < 0.05). Age (P = 0.037), sex (P < 0.001), height (P < 0.001), BMI (P = 0.008), and steatosis (P < 0.001) were independent variables for predicting the liver size. The liver size of persons with fatty liver was substantially more considerable than healthy people. The size of the liver was substantially linked with sex, age, BMI, fatty liver, and hepatic steatosis grade. A straightforward way to predict fatty liver is to use ultrasonography to determine the size of the liver.

Microemulsion co-delivering curcumin and DHA-rich algal oil alleviates nonalcoholic fatty liver disease

The combined effect of curcumin and docosahexaenoic acid (DHA) on liver injury has not yet been reported. We determined the synergistic effect of curcumin and DHA on the protection of WRL-68 cells from palmitic acid-induced injury, and on the inhibition of LX2 cells. A microemulsion to co-deliver both compounds was prepared by ultrasonic emulsification. Mice were fed a high-fat diet for 10 weeks to induce mild non-alcoholic fatty liver disease (NAFLD). At a dose of 5 mg/kg curcumin and 30 mg/kg DHA, the microemulsion successfully lowered serum triacylglycerol (TG) and low-density lipoprotein cholesterol levels, and significantly attenuated NAFLD. A pharmacokinetic study in rats showed that the microemulsion had a higher Cmax value for curcumin, a greater AUC0–24 value and a longer t1/2 value for both curcumin and DHA. This investigation provides a novel application of a combination of functional food ingredients to treat chronic liver disease.

Lack of association between nonalcoholic fatty liver disease and intracerebral hemorrhage: A community-based cohort study

BackgroundThe association between nonalcoholic fatty liver disease (NAFLD) and intracerebral hemorrhage (ICH) remains unclear. This study aimed to investigate whether NAFLD and its severity predict incident ICH. MethodsParticipants free of other liver diseases, prior stroke, myocardial infarction, cancer, or alcohol abuse in the Kailuan cohort were enrolled in this study. Abdominal ultrasonography was used to diagnose NAFLD and assess its severity. Participants were stratified into different groups including nonfatty liver, mild, moderate and severe NAFLD. Multivariable Cox proportional hazards regression models were used to evaluate the hazard ratios (HRs) and 95% CIs of ICH events in the 11-year follow-up. ResultsA total of 77,461 participants were enrolled in our study. Among them, NAFLD was diagnosed in 23,890 (30.83 %) participants, including 15,581 (20.11 %) with mild NAFLD, 6839 (8.83 %) with moderate NAFLD and 1470 (1.90 %) with severe NAFLD. We documented 692 ICH events during 848,579 person years of follow-up. Patients with more severe NAFLD tended to be older, had higher levels of BMI, higher proportions of hypertension, diabetes and other known risk factors for cerebrovascular disease. However, there was no significant associations between NAFLD, its severity and incident ICH events. Relative to nonfatty liver participants, the HRs for participants with mild NAFLD, moderate and severe NAFLD were 0.98 (95 % CI, 0.80 to 1.20), 1.19 (95 % CI, 0.92 to 1.54) and 1.29 (95 % CI, 0.81 to 2.06), respectively. ConclusionsNAFLD and its severity did not appear to be significantly associated with ICH after adjustment for potential risk factors.

Non-alcoholic Fatty Liver in Children and Adolescents in Saudi Arabia.

Objectives This study aims to describe the disease parameters of children and adolescents diagnosed with non-alcoholic fatty liver disease (NAFLD) in Saudi Arabia. It also investigates the disease's progression and compares clinical, biochemical, and radiological parameters at baseline and follow-up of patients with NAFLD. This study was done between two groups of patients: obese and those of average body weight. Methods A retrospective cohort study was conducted between 2014 and 2018 through retrieved data from medical records. It included all children aged between six to 18 years diagnosed with NAFLD. Medical history was taken from each medical record, liver function test results, cholesterol, blood pressure readings, and body weight. Data have been restored from King Abdullah Specialist Children's Hospital (KASCH)​, Security Forces Hospital (SFH), and King Khalid University Hospital (KKUH). Results A total of 116 subjects met the inclusion criteria; 65 (56%) were male, and 81 (70%) were obese. The majority of subjects (n=112) had mild NAFLD, with (71%) obese and(29%) non-obese, followed by moderate NAFLD with 50% among obese and non-obese (N=2), and non-alcoholic steatohepatitis (NASH) with 100% non-obese (N=2). Data showed that patients' proportion of obese to non-obese is 70% (N=81) to 30%(N=35), respectively. Conclusion NAFLDwas found to affect obese children and adolescents more than non-obese, and male patients had a higher proportion of NAFLD than females. Also, obese patients had more advanced stages of NAFLD than non-obese patients. Finally, most subjects had been diagnosed with mild stage while a few had developed NASH.

PREVALENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AMONG CORONARY ARTERY DISEASE PATIENTS AND ITS ASSOCIATION WITH CAD SEVERITY

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing concern due to its potential to lead to liver transplants and its association with cardiovascular disease (CVD). However, the relationship between NAFLD and CVD remains debated, and non-invasive diagnostic methods for NAFLD are recommended. This study aimed to estimate the prevalence of NAFLD among patients with CAD and explore the association between CAD severity and the probability of developing NAFLD.&#x0D; Methodology: A cross-sectional study was conducted among CAD patients. Patients with a history of infectious liver disease, pregnant or lactating individuals, and those with excessive alcohol consumption were excluded. Coronary angiography was performed to assess CAD severity using the Gensini score. Ultrasonography and non-invasive assessments, such as the Fibrosis-4 (FIB-4) index, were used to diagnose and stage NAFLD.&#x0D; Result: The study included 156 CAD patients, with 79 (50.6%) being male. Out of total, 31 (19.8%) had severe, 79(50.6%) had moderate, and 46 (29.48%) had mild NAFLD. Male patients showed a significantly higher prevalence of severe NAFLD compared to females. There was no significant difference in the mean age of CAD patients across NAFLD severities. Severe NAFLD was associated with higher mean Gensini scores and FIB-4 values compared to mild to moderate NAFLD patients. A positive correlation was found between Gensini score and FIB4, suggesting that Gensini score could be an alternative to FIB4 in diagnosing NAFLD severity among CAD patients.&#x0D; Conclusion: The study revealed a high prevalence of NAFLD among CAD patients, with severe NAFLD being associated with higher CAD severity.

Association of neck circumference-related indices with metabolic, atherogenic and liver function biomarkers in patients with non-alcoholic fatty liver disease: a cross-sectional study

ObjectiveThe present study aimed to establish the association of neck circumference (NC)-related indices with metabolic, atherogenic and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD).DesignCross-sectional study.SettingOutpatient clinics...

The correlation between NAFLD and serum uric acid to serum creatinine ratio.

With the prevalence of non-alcoholic fatty liver disease (NAFLD) increasing worldwide, many noninvasive techniques have been used to improve its diagnosis. Recently, the serum uric acid/creatinine (sUA/sCr) ratio was identified as an indicator of fatty liver disease. Therefore, we examined the relationship between sUA/sCr levels and ultrasound-diagnosed NAFLD in Korean adults. This study included 16,666 20-year-olds or older who received health checkups at a university hospital's health promotion center from January to December 2021. Among them, 11,791 non-patients with and without NAFLD were analyzed, excluding those without abdominal ultrasound, those without data on fatty liver, cancer, or chronic kidney disease severity, those with a history of alcohol abuse, and those with serum hs-CRP <5 mg/L. The odds ratio (OR) and 95% confidence interval (CI) of the sUA/sCr ratio according to the presence or absence of fatty liver disease and severity were calculated after correcting for confounding variables using logistic regression analysis. The receiver operating characteristic (ROC) curve and area under the curve (AUC) of the sUA/sCr ratio confirmed and compared the sensitivity and specificity of NAFLD and serum uric acid. sUA/sCr increased with fatty liver severity, and the post-correction OR in the NAFLD group was 1.183 (95% CI: 1.137-1.231) compared to the group without NAFLD. Concerning the fatty liver severity, the post-correction OR in the mild NAFLD group increased to 1.147 (95% CI: 1.099-1.196), and that in the moderate-to-severe NAFLD group increased to 1.275 (95% CI: 1.212-1.341) compared to the group without NAFLD. The sensitivity of sUA/sCr to fatty liver severity was 57.9% for the non-NAFLD group, 56.7% for the mild NAFLD group, and 59.0% for the moderate-to-severe NAFLD group; the specificity of sUA/sCr to fatty liver severity 61.4% for the non-NAFLD group, 57.3% for the mild NAFLD group, and 65.2% for the moderate-to-severe NAFLD group. NAFLD severity is associated with sUA/sCR.

Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension.

There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.

Effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood: A systematic review and meta-analysis.

The risk of metabolic disease in adulthood is not only attributed to an unhealthy lifestyle after birth but also to famine exposure during the foetal period. This systematic review and meta-analysis aimed to evaluate the effects of foetal exposure to famine as a risk factor for developing nonalcoholic fatty liver disease (NAFLD) in adulthood. Studies were retrieved from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to evaluate the effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood. Six studies involving 90,582 subjects were included in this meta-analysis. Foetal exposure to famine was associated with an increased risk of NAFLD(RR=1.17, 95% CI: 1.08-1.27, P < 0.0001). Exposure to famine during the foetal period significantly increased the incidence of NAFLD in women (RR=1.27, 95% CI: 1.16-1.40, P <0.00001), while similar results were not observed in the male subgroup (RR =0.99, 95% CI: 0.89-1.11, P=0.88). Foetal exposure to famine was associated with the risk of mild NAFLD (RR=1.17, 95% CI: 1.02-1.33, P=0.02) and moderate to severe NAFLD (RR=1.51, 95% CI: 1.16-1.98, P=0.002). Foetal exposure to famine is associated with an increased risk of NAFLD in adulthood. Women with NAFLD and moderate to severe NAFLD have a more robust association with foetal exposure to famine.

Histone Demethylation Profiles in Nonalcoholic Fatty Liver Disease and Prognostic Values in Hepatocellular Carcinoma: A Bioinformatic Analysis

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with multifactorial pathogenesis; histone demethylases (HDMs) are emerging as attractive targets. We identified HDM genes (including KDM5C, KDM6B, KDM8, KDM4A, and JMJD7) that were differentially expressed in NAFLD and normal samples by exploring gene expression profiling datasets. There was no significant difference in the expression of genes related to histone demethylation between mild and advanced NAFLD. In vitro and in vivo studies indicated that KDM6B and JMJD7 were upregulated at the mRNA level in NAFLD. We explored the expression levels and prognostic values of the identified HDM genes in hepatocellular carcinoma (HCC). KDM5C and KDM4A were upregulated in HCC compared to normal tissue, while KDM8 showed downregulation. The abnormal expression levels of these HDMs could provide prognostic values. Furthermore, KDM5C and KDM4A were associated with immune cell infiltration in HCC. HDMs were associated with cellular and metabolic processes and may be involved in the regulation of gene expression. Differentially expressed HDM genes identified in NAFLD may provide value to understanding pathogenesis and in the development of epigenetic therapeutic targets. However, on the basis of the inconsistent results of in vitro studies, future in vivo experiments combined with transcriptomic analysis are needed for further validation.

Circulating Short-Chain Fatty Acids and Non-Alcoholic Fatty Liver Disease Severity in Patients with Type 2 Diabetes Mellitus.

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a major global health concern. The increasing prevalence of NAFLD has been related to type 2 diabetes mellitus (T2D). However, the relationship between short-chain fatty acids (SCFAs) and NAFLD severity is ambiguous in T2D subjects. This study aimed to explore the association of SCFAs with the severity of NAFLD in T2D patients. (2) Methods: We employed echography to examine the severity of hepatic steatosis. The serum levels of nine SCFAs, namely, formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate, and methylvalerate, were measured using gas chromatography mass spectrometry. (3) Results: A total of 259 T2D patients was enrolled in this cross-sectional study. Of these participants, 117 with moderate to severe NAFLD had lower levels of formate, isobutyrate, and methylbutyrate than the 142 without NAFLD or with mild NAFLD. Lower circulating levels of isobutyrate and methylbutyrate were associated with an increased severity of NAFLD. A relationship between NAFLD severity and circulating isobutyrate and methylbutyrate levels was found independently of a glycated hemoglobin (HbA1C) level of 7.0%. (4) Conclusion: Circulating levels of isobutyrate and methylbutyrate were significantly and negatively correlated with NAFLD severity in the enrolled T2D patients. SCFAs may be related to NAFLD severity in T2D patients.

Oxysterol-binding protein-like 3 is a novel target gene of peroxisome proliferator-activated receptor γ in fatty liver disease

Oxysterol-binding protein-like 3 (OSBPL3) plays a key role in the development of fatty liver disease. Herein, we found that OSBPL3 is highly expressed in the fatty liver of humans and mice. Although high expression of Osbpl3 was observed in the fatty liver of type 2 diabetic ob/ob mice, liver-specific Pparg knockout ameliorated this increase in these mice. Moreover, high hepatic Osbpl3 expression was observed in other mice models of fatty liver disease, such as leptin receptor-mutant db/db and alcohol-fed mice. Analysis of the human liver transcriptome data revealed that hepatic OSBPL3 expression is higher in patients with advanced non-alcoholic fatty liver disease (NAFLD) when compared to those with mild NAFLD. Reporter and electrophoretic mobility shift assays showed that PPARγ positively regulates Osbpl3 transcription by binding to the two functional PPARγ-responsive elements present in the 5′ upstream region. Overall, our results indicate that Osbpl3 is a novel PPARγ target in the fatty liver.

Relationship of Helicobacter pylori Infection with Nonalcoholic Fatty Liver Disease: A Meta-Analysis.

Helicobacter pylori (H. pylori) and nonalcoholic fatty liver disease (NAFLD) have become increasingly recognized, both of which affect human health globally. The association of H. pylori infection with NAFLD remains unclear. PubMed, EMBASE, and Cochrane Library databases were searched. Only a random-effects model was used. Odds ratios (ORs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for the combined estimates of raw data. Adjusted ORs (aORs) and hazard ratios (aHRs) with 95% CIs were calculated for the combined estimates of data adjusted for confounders. Thirty-four studies with 218573 participants were included. Based on unadjusted data from 26 cross-sectional studies and 3 case-control studies, H. pylori infection was significantly associated with the presence of NAFLD (OR = 1.26, 95% CI = 1.17-1.36, P < 0.001). Based on adjusted data from 15 cross-sectional studies and 1 case-control study, H. pylori infection was significantly associated with the presence of NAFLD (aOR = 1.25, 95% CI = 1.08-1.44, P < 0.001). Compared with control subjects without NAFLD, patients with moderate (OR = 1.67, 95% CI = 1.17-2.39, P = 0.005) and severe (OR = 1.71, 95% CI = 1.30-2.24, P < 0.001) NAFLD, but not those with mild NAFLD (OR = 1.14, 95% CI = 0.9-1.45, P = 0.286), had significantly higher proportions of H. pylori infection. The association of H. pylori infection with the occurrence of NAFLD was statistically significant based on adjusted data from 3 cohort studies (aHR = 1.18, 95% CI = 1.05-1.34, P = 0.007), but not based on unadjusted data from 3 cohort studies (RR = 1.41, 95% CI = 0.80-2.48, P = 0.237). H. pylori infection is associated with NAFLD, especially moderate and severe NAFLD. The impact of H. pylori eradication on the prevention of NAFLD should be further explored.

Association between Regional Body Muscle Mass and Non-Alcoholic Fatty Liver Disease: An Observational Study Using Data from the REACTION Study

Background and aims: Regional muscle distribution is associated with abdominal obesity and metabolic syndrome. However, the relationship between muscle distribution and nonalcoholic fatty liver disease (NAFLD) remains unclear. This study was to determine the relationship between regional muscle distribution and the risk and severity of NAFLD. Methods: This cross-sectional study ultimately included 3161 participants. NAFLD diagnosed by ultrasonography was classified into three groups (non, mild, and moderate/severe). We estimated the regional body muscle mass (lower limbs, upper limbs, extremities, and trunk) through multifrequency bioelectrical impedance analysis (BIA). The relative muscle mass was defined as the muscle mass adjusted for the body mass index (BMI). Results: NAFLD participants accounted for 29.9% (945) of the study's population. Individuals with a higher lower limb, extremity, and trunk muscle mass had a lower risk of NAFLD (p < 0.001). Patients with moderate/severe NAFLD had a lower muscle mass of the lower limbs and trunk than patients with mild NAFLD (p < 0.001), while the muscle mass of the upper limbs and extremities did not differ significantly between the two groups. Moreover, similar results were found for both sexes and among different age groups. Conclusions: A higher muscle mass of the lower limbs, extremities, and trunk was negatively associated with the risk of NAFLD. A lower muscle mass of the limbs and trunk was inversely associated with the severity of NAFLD. This study provides a new theoretical basis for the development of individualized exercise prescriptions for the prevention of NAFLD in non-NAFLD patients.

Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis.

It is generally believed that complement system is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, complement system contains a variety of complement components, and the relationship between complement components and the risk and severity of NAFLD is inconsistent. The aim of this meta-analysis was to evaluate the association of complement components with the risk and severity of NAFLD. We searched PubMed, Embase, Cochrane Library, Google Scholar, Scopus, and ZhiWang Chinese databases from inception to May 2022 for observational studies reporting the risk of NAFLD with complement components. Random-effects meta-analysis was used to obtain pooled estimates of the effect due to heterogeneity. We identified 18 studies with a total of 18560 included subjects. According to recent studies, levels of complement component 3 (C3) (mean difference (MD): 0.43, 95% confidence interval (CI) 0.26-0.60), complement component 4 (C4) (MD: 0.04, 95% CI 0.02-0.07), complement component 5(C5) (MD: 34.03, 95% CI 30.80-37.27), complement factor B (CFB) (MD: 0.22, 95% CI 0.13-0.31) and acylation stimulating protein (ASP) (standard mean difference (SMD): 5.17, 95% CI 2.57-7.77) in patients with NAFLD were significantly higher than those in the control group. However, no statistical significance was obtained in complement factor D (CFD) levels between NAFLD and non-NAFLD (MD=156.51, 95% CI -59.38-372.40). Moreover, the levels of C3, C5, CFB, and ASP in patients with moderate and severe NAFLD were significantly higher than those in patients with mild NAFLD. Except for C4 and CFD, the included studies did not explore the changes in the severity of NAFLD according to the concentration of C4 and CFD. This meta-analysis demonstrates that an increase in complement components including C3, C5, CFB, and ASP is associated with an increased risk and severity of NAFLD, indicating that they may be good biomarkers and targets for the diagnosis and treatment of NAFLD. PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42022348650.

TRIM59 promotes steatosis and ferroptosis in non-alcoholic fatty liver disease via enhancing GPX4 ubiquitination

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease around the world. However, no specific medicine has been approved for NAFLD treatment. Our study was conducted to explore the role and mechanism of TRIM59 in NAFLD, aiming to provide a novel target for NAFLD treatment. Here, the expression of TRIM family members was detected in 10 mild and severe NAFLD tissues as well as 10 normal tissues. TRIM59 expression was verified in 10 normal tissues and 25 mild and severe NAFLD tissues. Palmitic acid and high-fatty diet were used for the construction of NAFLD models. Oil Red O staining was used to detect the level of steatosis. The content of TNF-α, IL-6, and IL-8 was measured to reflect the level of inflammation. Lipid reactive oxygen species was estimated by flow cytometry. We found that TRIM59 was highly expressed in NAFLD tissues compared with normal liver tissues. The inhibition of TRIM59 could inhibit the steatosis and inflammation in NAFLD, whereas its overexpression exhibited reversed effects. The application of ferroptosis inhibitor, deferoxamine, could markedly ameliorate steatosis and inflammation, which was mediated by overexpressed TRIM59. Besides, TRIM59 was demonstrated to interact with GPX4 and promoted its ubiquitination. The overexpression of GPX4 could significantly reverse the pathogenic effects of TRIM59 in NAFLD. Additionally, the inhibition of TRIM59 appeared to be a promising strategy to ameliorate NAFLD in mice model. In summary, our study revealed that TRIM59 could promote steatosis and ferroptosis in NAFLD via enhancing GPX4 ubiquitination. TRIM59 could be a potential target for NAFLD treatment.