Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and its prevalence has risen sharply. However, whether nutrition, dietary strategies, exercise, lifestyle and environment have preventive value for NAFLD remains unclear.

Through searching 4 databases (PubMed, Web of Science, Embase and the Cochrane Library) from inception to January 2025, we selected studies about nutrition, dietary strategies, exercise, lifestyle and environment in the prevention of NAFLD and conducted a narrative review on this topic.

Reasonable nutrient intake encompassing macronutrients and micronutrients have an independent protective relationship with NAFLD. Besides, proper dietary strategies including mediterranean diet, intermittent fasting diet, ketogenic diet, and dietary approaches to stop hypertension diet have their inhibitory effects on the developmental process of NAFLD. Moreover, right exercises including walking, jogging, bicycling, and swimming are recommended for the prevention of NAFLD because they could effectively reduce weight, which is an important risk factor for NAFLD, and improve liver function. In addition, embracing a healthy lifestyle including reducing sedentary behavior, not smoking, sleeping well and brushing teeth regularly is integral since it not only could reduce the risk of NAFLD but also significantly contribute to overall prevention and control. Finally, the environment, including the social and natural environments, plays a potential role in NAFLD prevention.

Nutrition, dietary strategies, exercise, lifestyle and environment play an important role in the prevention of NAFLD. Moreover, this review offers comprehensive prevention recommendations for people at high risk of NAFLD.

Lipid accumulation in hepatocytes is reduced by the activation of the peroxisome proliferator-activated receptor (PPAR) α, which is associated with increased lysosomal acid lipase (LAL) activity, transcription factor EB (TFEB) expression, and mitochondrial β-oxidation.Aim of the study was to assess whether the three isoforms of PPAR, i.e. α, δ and γ, share the same ability to reduce lipid accumulation in hepatocytes and to clarify the involvement of autophagy activation, lysosomal hydrolysis, and mitochondrial β-oxidation in lipid clearance induced by PPARs.

HepG2 cells were treated with oleate/palmitate (O/P) to induce lipid accumulation and exposed to the PPARα agonist fenofibric acid, the γ agonist pioglitazone, the δ agonist seladelpar, or the dual α/γ agonist saroglitazar.

The treatment of HepG2 cells with fenofibric acid, pioglitazone, seladelpar, or saroglitazar halved lipid accumulation induced by O/P. PPAR agonists increased TFEB, p62, and LC3 expression and rescued LAL impairment induced by O/P. Moreover, PPAR agonists significantly increased mitochondrial mass and the expression of genes involved in mitochondrial dynamics and fatty acid catabolism. Interestingly, PPAR agonists lost their ability to reduce lipid accumulation when autophagic flux, LAL activity, or fatty acid transport in the mitochondria were blocked by specific inhibitors.

All PPAR agonists were able to promote the clearance of lipids in cells loaded with long-chain fatty acids. The key role of acid hydrolysis to generate fatty acids, which can be then catabolized in the mitochondria, and the ability of the PPAR system to sustain each phase of this clearing process were elucidated.

Heart failure with reduced ejection fraction (HFrEF) and metabolic dysfunction-associated steatotic liver disease (MASLD) are both associated with liver fibrosis. HFrEF patients may develop liver fibrosis due to hepatic congestion, MASLD, or a combination of both. The Fibrosis-4 (FIB-4) score calculated using age, aspartate aminotransferase, alanine aminotransferase, and platelet count, serves as a screening tool for advanced liver fibrosis. This study examines the association between the FIB-4 score and all-cause mortality, cardiovascular mortality, and major adverse liver outcomes (MALO) in patients with HFrEF.

This study included 4523 HFrEF patients from the Danish Heart Failure Registry. Based on FIB-4 score, 25.5 % were low-risk, 45.7 % were indeterminate-risk, and 28.8 % were high-risk for advanced liver fibrosis. After five years, the cumulative incidence of all-cause mortality was 43 % for the high-risk group, 36 % for the indeterminate-risk group, and 23 % for the low-risk group. The indeterminate-risk and high-risk group had an increased hazard ratio (HR) for all-cause mortality (HR 1.33, 95 % confidence interval [CI] 1.16-1.52; HR 1.51, 95 % CI 1.31-1.74) compared to the low-risk group. Similarly, HRs were elevated for cardiovascular mortality (HR 1.61, 95 % CI 1.27-2.05; HR 2.14, 95 % CI 1.67-2.74) and MALO (HR 1.77, 95 % CI 1.01-3.31; HR 2.54, 95 % CI 1.43-4.52).

A high FIB-4 score in patients with HFrEF is associated with increased mortality and MALO.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to cognitive decline and dementia risk. We aimed to investigate the association between MASLD and brain ageing and explore the role of low-grade inflammation.

Within the UK Biobank, 30 386 chronic neurological disorders-free participants who underwent brain magnetic resonance imaging (MRI) scans were included. Individuals were categorised into no MASLD/related SLD and MASLD/related SLD (including subtypes of MASLD, MASLD with increased alcohol intake [MetALD] and MASLD with other combined aetiology). Brain age was estimated using machine learning by 1079 brain MRI phenotypes. Brain age gap (BAG) was calculated as the difference between brain age and chronological age. Low-grade inflammation (INFLA) was calculated based on white blood cell count, platelet, neutrophil granulocyte to lymphocyte ratio and C-reactive protein. Data were analysed using linear regression and structural equation models.

At baseline, 7360 (24.2%) participants had MASLD/related SLD. Compared to participants with no MASLD/related SLD, those with MASLD/related SLD had significantly larger BAG (β = 0.86, 95% CI = 0.70, 1.02), as well as those with MASLD (β = 0.59, 95% CI = 0.41, 0.77) or MetALD (β = 1.57, 95% CI = 1.31, 1.83). The association between MASLD/related SLD and larger BAG was significant across middle-aged (< 60) and older (≥ 60) adults, males and females, and APOE ɛ4 carriers and non-carriers. INFLA mediated 13.53% of the association between MASLD/related SLD and larger BAG (p < 0.001).

MASLD/related SLD, as well as MASLD and MetALD, is associated with accelerated brain ageing, even among middle-aged adults and APOE ɛ4 non-carriers. Low-grade systemic inflammation may partially mediate this association.

This study investigates the link between blood manganese (Mn) levels and non-alcoholic fatty liver disease (NAFLD) in a U.S. adult population.

The role of manganese in NAFLD remains poorly understood. However, the NHANES database offers valuable data on blood manganese levels and metabolic status for 6278 subjects in the United States, facilitating the study of this relationship.

To investigate the relationship between blood manganese (Mn) levels and NAFLD, we conducted a t-test to compare Mn levels between participants with and without NAFLD. Participants were categorized into quartiles based on their blood Mn levels. We then employed multiple logistic regression analysis and sensitivity analyses to further examine the Mn-NAFLD relationship.

The NAFLD group had a significantly higher blood manganese level (10.0 ± 3.7 μg/L, P < 0.05) than the control group. Stratifying 6278 subjects by blood manganese quartiles showed increased NAFLD odds in higher quartiles (Q2-Q4) vs. Q1 (ORs: 1.49, 1.37, 1.49). The Mn-NAFLD relationship followed an inverted L-shaped curve, peaking at 8.52 μg/L.

Elevated levels of manganese in the blood have been shown to be associated with an increase in the risk of NAFLD, and blood manganese values can be utilized as a marker for assessing NAFLD.

The transition in terminology from fatty liver disease to metabolic dysfunction-associated steatotic liver disease (MASLD) marks a considerable evolution in diagnostic standards. This new definition focuses on liver fat accumulation in the context of overweight/obesity, type 2 diabetes, or metabolic dysfunction, without requiring the exclusion of other concurrent liver diseases. The new definition also provides clear guidelines for defining alcohol consumption in relation to the disease. MASLD is currently acknowledged as the most widespread liver disorder globally, affecting ~25% of the population. Despite the extensive array of clinical trials conducted in recent years, the number of approved treatments for metabolic dysfunction-associated fatty liver disease is very limited. In the review critically evaluates the results of clinical trials of related drugs and assesses the future directions for drug development trials. The renaming of MASLD presents new challenges and opportunities for the design of clinical trials and the selection of target populations for drug development.

Compensated cirrhosis due to metabolic dysfunction-associated steatotic liver disease (CC-MASLD) increases morbidity and mortality risk but has no aetiology-specific treatment. We investigated the safety and efficacy signals of severe energy restriction.

In this randomised controlled trial, adults with CC-MASLD and obesity in a tertiary hepatology centre were randomised 2:1 to receive one-to-one remote dietetic support with a low-energy (880 kcal/day, 80 g protein/day) total diet replacement programme for 12 weeks and stepped food reintroduction for another 12 weeks or standard of care (SoC). Given the exploratory nature of the study, three pre-defined co-primary outcomes were used to assess safety and efficacy signals: severe increases in liver biochemistry, changes in iron-corrected T1, and changes in liver stiffness on magnetic resonance elastography. Changes in liver steatosis on magnetic resonance imaging, physical performance based on the physical performance test and liver frailty index, and changes in fat-free mass were secondary outcomes. Magnetic resonance outcomes were assessed blind.

Between February 2022 and September 2023, 17 participants (36% female, median [IQR] age 58 [7.5] years) were randomised to SoC (n = 6) or intervention (n = 11). The trial stopped earlier than planned due to slow recruitment rate. 91% and 94% of participants completed the intervention and attended the 24-week follow-up, respectively. Compared with the SoC, the between-group weight change in the intervention was -11.9 kg (95% CI: -17.2, -6.6, p < 0.001) at 24 weeks. Liver biochemistry markers (alanine transaminase, aspartate transaminase, and total bilirubin) were stable in everyone throughout the trial. Iron-corrected T1 and steatosis significantly reduced (-149.9 ms [95% CI -258.1, -41.7, p = 0.01] and -6% [95% CI -11.3, -0.6, p = 0.03], respectively). There were no between-group differences in changes in liver stiffness (0.2 kPa [95% CI -1.1, 1.6]), the physical performance test (1.5 points [95% CI -1.9 to 4.9], p = 0.70) or the liver frailty index (0 [95% CI -0.6 to 0.6], p = 0.97). Compared with SoC, absolute fat-free mass reduced (-3.2 kg [95% CI -6 to -0.3], p = 0.04) but relative fat-free mass as percentage of total body weight increased (5.4% [95% CI 0.5 to 10.3], p = 0.046). No participant met the pre-defined safety criteria for enhanced observation or intervention discontinuation. There was no between-group differences in changes in cardiovascular markers and no evidence of hepatic decompensation or serious adverse events.

Severe energy restriction appears a safe option to achieve significant weight loss and reduce liver fat without adverse effects in people with CC-MASLD. A larger study is needed to confirm these findings.

ISRCTN13053035, prospectively registered, overall study status: closed.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major health risk and a serious worldwide issue. MAFLD typically arises from aberrant lipid metabolism, insulin resistance, oxidative stress, and inflammation. However, subjacent causes are multifactorial. The gut has been proposed as a major factor in health and disease, and over the last decade, bacterial strains with potentially beneficial effects on the host have been identified. In vitro cell models have been commonly used as an early step before in vivo drug assessment and can confer complementary advantages in gut and liver health research. In this study, several selected strains of the order Bacteroidales were used in a three-cell line in vitro analysis (HT-29, Caco-2, and HepG2 cell lines) to investigate their potential as new-generation probiotics and microbiota therapeutics. Antimicrobial activity, a potentially useful trait, was studied, and the results showed that Bacteroidales can be a source of either wide- or narrow-spectrum antimicrobials targeting other closely related strains. Moreover, Bacteroides sp. 4_1_36 induced a significant decrease in gut permeability, as evidenced by the high TEER values in the Caco-2 monolayer assay, as well as a reduction in free fatty acid accumulation and improved fatty acid clearance in a steatosis HepG2 model. These results suggest that Bacteroidales may spearhead the next generation of probiotics to prevent or diminish MAFLD.

Noninvasive assessment of liver fat content is crucial due to the high global prevalence of nonalcoholic fatty liver disease. Algorithms based on ultrasound (US) attenuation coefficient (AC) for estimating liver fat content are commercially available, but a lack of consensus exists regarding the best estimation protocol. The aim of our study was to evaluate the influence of the size of the region of interest (ROI) on the US AC.A prospective study was conducted. An abdominal US was done for 86 outpatients. A sampling box was positioned within the liver parenchyma, approximately 2 cm beneath the liver capsule with a ROI, measuring about 2 × 4 cm and then 4 × 5 cm, precisely placed at the center of this sampling box. Five readings of the AC were captured, and the average of these measurements was employed to assess the severity of hepatic steatosisA statistically significant difference between AC with 2 different ROI sizes was shown (P < 0.001) with AC values with 2 × 4 cm ROI were higher than those obtained with 4 × 5 cm ROI (AC mean 0.668 VS 0.653). However, the agreement between AC values obtained with 2 different ROI sizes was excellent (correlation coefficient 0.941)An ROI size dependence is observed in the measurement of AC in the liver. A standardized acquisition protocol with a fixed size of the ROI needs to be developed to minimize differences in AC measurements and to assess changes in serial measurements reliably.

MAFLD is highly prevalent among overweight and obese individuals. Recently, the American Heart Association proposed a new measure of cardiovascular health (Life's Essential 8). This study investigated the relationship between the Life's Essential 8 (LE8) and MAFLD, all-cause and cardiovascular mortality in these populations, exploring the mediating role of inflammation and insulin resistance. This retrospective study used data from the National Health and Nutrition Examination Survey (NHANES, 2007-2018), including 6,885 overweight and obese individuals. LE8 scores were categorized into low, medium, and high groups. Weighted logistic regression and Cox proportional hazards models assessed the relationships between LE8, MAFLD, and mortality. Mediation analyses explored the roles of inflammation and insulin resistance, and weighted restricted cubic spline (RCS) regression examined potential nonlinear associations. Kaplan-Meier survival analysis evaluated survival rates across LE8 groups, and subgroup analyses assessed interactions with demographic characteristics. Additionally, ROC curves were used to explore the predictive accuracy of various inflammation and insulin resistance biomarkers. In model 3, compared to the low LE8 group, the prevalence of MAFLD in the highest LE8 group was reduced by 89% (OR = 0.11; 95% CI: 0.06, 0.20). HOMA-IR mediated 72.26% of the mediation effect. Various inflammation markers, including CRP, hs-CRP, SII, and SIRI indices, mediated effects ranging from 3 to 12%. Compared to the low LE8 group, the highest LE8 group had a 58% reduction in all-cause mortality and a 90% reduction in cardiovascular mortality. Kaplan-Meier analysis showed that the higher LE8 groups had significantly higher survival rates than the low LE8 group. Inflammatory markers mediated 5-17% of the mediation effects. Restricted cubic spline (RCS) curves revealed a non-linear relationship between LE8 and MAFLD. Age interacted with LE8 in several subgroup analyses. ROC curves showed that HOMA-IR had strong predictive accuracy for MAFLD, while SIRI demonstrated potential advantages in predicting mortality risk. In overweight/obese populations, LE8 scores were negatively associated with the prevalence of MAFLD, and risk of mortality. These findings emphasize the importance of maintaining high levels of LE8 scores for primary prevention in overweight/obese populations.

Obesity represents a chronic pro-inflammatory status that contributes to accelerated atherosclerosis and cell aging. Besides the widely used C-reactive protein and ferritin, other inflammatory markers have gained attention, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), which are related with the degree of inflammation in various pathological conditions, including obesity and its comorbidities.

To compare and monitor the levels of NLR and PLR before and after sleeve gastrectomy (SG).

Retrospective study that included a total of 622 patients with obesity who underwent SG as primer bariatric surgery in our center. Data regarding the presence of comorbidities, including type 2 diabetes (T2D), high blood pressure (HBP) and non-alcoholic fatty liver disease (NAFLD), variations in body weight and body mass index (BMI), and biochemical markers of inflammation, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein (CRP) were gathered. Values of NLR and PLR were correlated with weight loss and prognosis of comorbidities within the postoperative period.

The sample was predominantly female (79.3%) with average age 36.91±10.04 years, with comorbidities including HBP (25.1%), T2D (8.0%), and NAFLD (80.1%). Patients with HBP showed reduced NLR and CRP post-intervention, while those with T2D experienced decreased CRP but increased PLR. Correlation analysis found no significant correlation between BMI/weight changes and NLR but significant correlation with PLR. Post-surgery, NLR decreased for previously NAFLD patients, and PLR increased.

According to the results, patients with obesity present a significant decrease in NLR and an increase in PLR after SG.

We investigated the association between fasting serum and urinary nitric oxide metabolite (NOx) levels and fatty liver index (FLI), a non-invasive surrogate of non-alcoholic fatty liver disease (NAFLD) and liver steatosis.

This cross-sectional study included 598 adults (aged≥18 years, 48.6% men) who participated in the Tehran Lipid and Glucose Study (2015-2017). Serum and urine NOx concentrations were quantified using a spectrophotometric method following the Griess reaction. FLI values were calculated using γ-glutamyl transferase, triglycerides, body mass index, and waist circumference. The associations between urinary and serum NOx-to-creatinine (Cr) ratio [either as a categorical variable, i.e., tertiles, or as a continuous variable, i.e., per 1 SD) with NAFLD (i.e., FLI≥60) were assessed using multivariable-adjusted binary logistic regression.

The study participants' mean (SD) age was 42.5±14.6 y. The mean (SD) of serum and urinary NOx was 37.5±16.7 and 1310±751 μmol/L, respectively. The mean (SD) of FLI was 43.3±30.2, and the prevalence of NAFLD was 32.4%. Serum NOx-to-Cr ratio was not associated with the chance of having NAFLD (OR=1.66, 95% CI=0.98-2.82; P value=0.058). Higher urinary NOx-to-Cr ratio was significantly associated with a reduced probability of NAFLD (OR=0.61, 95% CI=0.38-0.95, and OR=0.54, 95% CI=0.34-0.87, in the second and third tertiles).

Higher dietary nitrate (NO3) intake, indicated by increased urinary NOx-to-Cr ratio, is associated with a reduced probability of NAFLD, highlighting the potential role of dietary NO3 in liver health.

The transition from metabolic dysfunction-associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is characterized by a chronic low-grade inflammation, involving activation of resident macrophages (Kupffer cells; KC) and recruitment of infiltrating macrophages. Macrophages produce cytokines and, after induction of Cyclooxygenase 2 (COX-2), the key enzyme of prostanoid synthesis, prostaglandin E2 (PGE2). PGE2 modulates cytokine production in an autocrine and paracrine manner, therefore playing a pivotal role in regulating inflammatory processes. Changes in the hepatic macrophage pool during MASLD progression to MASH could influence PGE2- and cytokine-mediated signaling processes. The aim of this study was to characterize these changes in mice with diet-induced MASH and further elucidate the role of COX-2-dependently formed PGE2 on the inflammatory response in different macrophage populations of mice with a macrophage-specific COX-2-deletion.

Male, 6-7-week-old wildtype mice were fed either a Standard or high-fat, high-cholesterol MASH-inducing diet for 4, 12 and 20 weeks. Liver macrophages were isolated and analyzed by flow cytometry. For in vitro experiments primary KC, peritoneal macrophages (PM) and Bone-marrow-derived macrophages (BMDM) were isolated from macrophage-specific COX-2-deficient and wildtype mice and treated with lipopolysaccharide (LPS) and/or PGE2.

During MASH-development, the proportion of KC (Clec4F+Tim4+) decreased, while the proportion of monocyte-derived macrophages (Clec4F-Tim4-) and monocyte-derived cells exhibiting a phenotype similar to KC (Clec4F+Tim4-) significantly increased over time. In vitro experiments showed that exogenous PGE2 completely abrogated the LPS-induced mRNA expression and secretion of tumor necrosis factor-alpha (TNF-α) in primary KC, PM and BMDM from wildtype mice. PM and BMDM, as in vitro models for infiltrating macrophages, were more sensitive to PGE2 compared to KC. Deletion of COX-2 in all macrophage populations led to an impaired PGE2-dependent feedback inhibition of TNF-α production. LPSinduced TNF-α mRNA expression was higher compared to the respective wildtype macrophage population.

The current study, using a murine MASH model, indicates that PGE2 may have a protective, anti-inflammatory effect, especially by inhibiting the expression of pro-inflammatory cytokines such as TNFα in infiltrating monocyte-derived macrophages. An inhibition of endogenous PGE2 synthesis in macrophages by pharmacological inhibition of COX-2 could potentially increase inflammation and promote the progression of MASH.

Mean platelet volume (MPV) has been reported significantly higher in patients with metabolic dysfunction associated steatotic liver disease (MASLD), suggesting a thrombogenic effect with an inconclusive link to excess risk for cardiovascular disease (CVD). The aim of this cross-sectional study was to elucidate the role of MPV in MASLD and review the literature.

A cohort of consecutive biopsy-proven MASLD patients was retrospectively investigated for possible associations of MPV with histological features of the disease and, separately, with patients' estimated risk for CVD. CVD Risk was assessed with three different scores: QRISK2, HellenicSCORE II and NAFLD CV Risk. Laboratory investigation included calculation of insulin resistance with the Homeostasis Model Assessment (HOMA) and measurement of serum adiponectin in a subgroup of patients.

In a total of 139 MASLD patients, 56 (40.3%) with advanced fibrosis (F3/F4) steatohepatitis were included. MPV exceeded the upper limit of normal (=10 fl) in a significant proportion of study participants (n = 28.1%), with an overall mean of 9.4 ± .9 fl. Statistically significant associations of MPV with platelet count (Pearson correlation, p < .001), with fibrosis stage (one-way ANOVA, p = .040), with adiponectin (Spearman's correlation, p = .033), and all three different CVD Risk scores were found. Finally, a strong negative correlation was detected between serum adiponectin and CVD Risk scores.

In this study's cohort of MASLD patients, high MPV was associated with higher fibrosis stages and with increased estimated risk for CVD. Correlations of serum adiponectin to MPV and CVD risk scores support its implication as a cytokine-mediator that has to be further studied.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), has become a great public healthcare burden and is closely associated with type 2 diabetes (T2D) and insulin resistance. However, there is no specific treatment for MASLD. Recent clinical findings have indicated a possible beneficial effect of sodium-glucose cotransporter 2 (SGLT2) on MASLD. This study aimed to investigate the effects of dapagliflozin (Dapa) on MASLD in T2D mice.

Four-week-old ob/ob mice were fed with a high-fat diet (HFD) for 8 weeks and then randomly divided into two groups supplemented with Dapa or vehicle for another 12 weeks. C57BL/6J mice fed with a standard chow diet (CD) were used as the control group. Metabolic outcomes, liver pathology, lipidomics and insulin signaling were assessed.

We showed that Dapa reduced body weight and ameliorated hyperglycemia and fatty liver in obese diabetic ob/ob mice. Compared with vehicle, dapa improved the NAFLD activity score mainly by attenuating fat deposition. Importantly, Dapa decreased the expression levels of mRNAs and proteins related to fatty acid synthesis and increased the expression levels of β-oxidation-related factors. We also found that Dapa treatment improved insulin signaling by increasing PI3K and Akt phosphorylation.

Dapa protects mice from diet-induced weight gain and improves hepatic lipotoxicity and insulin resistance in diabetic MASLD mice. Our results revealed that Dapa has a therapeutic effect on MASLD and could be a potential drug candidate for the treatment of MASLD.

To perform a systematic review and meta-analysis to evaluate the diagnostic performance of Ultrasound-Derived Fat Fraction (UDFF) in detecting hepatic steatosis using Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) as the reference standard.

Relevant databases were searched through November 2024. Studies that evaluated the UDFF to detect hepatic steatosis using MRI-PDFF as the reference standard met the inclusion criteria. Our primary outcome was the sensitivity and specificity of UDFF compared to MRI-PDFF in distinguishing steatosis from non-steatosis. Analyses were performed using a bivariate random-effects approach, and heterogeneity was considered substantial if I2 > 50%. A sensitivity analysis was performed to detect potential studies that contribute to heterogeneity.

Nine studies comprising 1150 patients (mean age range, 14-62 years; 51.2% women) were included. Eight studies were performed using the same vendor platform. The pooled sensitivity of UDFF for detecting hepatic steatosis was 90.4% (95% CI: 84.0%, 94.4%), and the pooled specificity was 83.8% (95% CI: 75.1%, 89.8%). The AUC for the summary receiver-operating characteristic curve was 0.93 (95% CI: 0.83, 0.95). Heterogeneity among the studies was low (I² = 22.2%).

UDFF demonstrates high sensitivity and specificity for detecting hepatic steatosis, supporting its value as a noninvasive tool for screening.

Question Small individual studies suggest that US-Derived Fat Fraction (UDFF) may effectively detect hepatic steatosis compared to MRI, but no meta-analysis has been performed. Findings In nine studies including 1150 patients, UDFF demonstrated high pooled sensitivity (90.4%) and specificity (83.8%) relative to MRI with low between-study heterogeneity. Clinical relevance UDFF demonstrates high diagnostic accuracy compared with MRI, supporting its use as a noninvasive tool with potentially lower cost and wider availability for large-scale screening of hepatic steatosis.

Non-alcoholic fatty liver disease (NAFLD) has become a public health issue worldwide. Dietary polyphenols are naturally occurring plant active ingredients and are widely employed in the treatment of NAFLD. However, the therapeutic effect is still controversial. In this study, a network meta-analysis (NMA) was performed to appraise the effects of various polyphenols on metabolic indices of NAFLD.

PubMed, Embase, the Cochrane Library, and Web of Science were retrieved for English studies on dietary polyphenols in the treatment of NAFLD. Outcome measures were extracted from the included studies and compared using a Bayesian NMA model, encompassing body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and necrosis factor alpha (TNF-α).

In total, 54 randomized controlled trials (RCTs) were included in this study, including 3,132 participants. It involved 13 single (or combined) dietary polyphenols. Naringenin could reduce serum TC (surface under the cumulative ranking curve: 94.59%) and TG (99.00%) in NAFLD patients. Catechin could decrease BMI (77.74%) and serum ALT (94.21%), AST (93.56%), TC (92.26%), and increase HDL-C (93.72%). Dihydromyricetin (DHM) was effective in reducing serum LDL-C (73.22%), and quercetin decreased serum TNF-α (99.47%).

Catechin may be the most appropriate dietary polyphenol supplement for NAFLD. Future studies should incorporate more RCTs to further validate the efficacy of dietary polyphenols (like DHM and quercetin), which are limited in sample sizes, in treating NAFLD. On the other hand, it is essential to investigate improvements in the bioavailability of these dietary polyphenols and to clarify their safety profiles.

This study aimed to investigate the levels of Faecalibacterium prausnitzii (F. prausnitzii) and Eubacterium rectale (E. rectale) in patients with non-alcoholic fatty liver disease (NAFLD) and evaluate the impact of dietary intervention on these bacterial populations.

An interventional study was conducted with 38 NAFLD patients recruited from the Marmara University Gastroenterology Institute. Participants were divided into two groups: a diet intervention group (n = 21) and a control group (n = 17). The dietary intervention consisted of a balanced diet containing 50-55 % carbohydrates, 30-35 % fats, and 15-20 % protein. Fecal samples were collected at baseline and after six weeks for both groups, and bacterial quantification was performed via deoxyribonucleic acid (DNA) analysis of the fecal samples.

In the diet intervention group, a significant increase in E. rectale abundance was observed after six weeks (p = 0.008). Additionally, intakes of dietary fiber, vitamin E, vitamin C, and thiamine were significantly higher in the intervention group compared to the control group by the end of the study (p < 0.05). However, no significant changes were detected in F. prausnitzii levels in either group.

The findings demonstrate that dietary intervention can significantly increase E. rectale abundance in NAFLD patients, while F. prausnitzii levels remain unaffected. These results highlight the selective influence of dietary modifications on gut bacterial populations, offering potential implications for the management of NAFLD.

The close interplay between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes supports the need to identify beneficial combination therapies of antidiabetic medications targeted for the treatment of MASLD. This study aimed to investigate the complementary effects of combination therapy with pioglitazone (PIO) and empagliflozin (EMPA) on MASLD in individuals with type 2 diabetes.

In a randomized, open-label trial, 50 participants with type 2 diabetes and MASLD were assigned 1:1:1 to receive PIO 15 mg, EMPA 10 mg, or a combination (PIO 15 mg plus EMPA 10 mg) daily for 24 weeks. Liver fat fraction and stiffness were evaluated using magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE), respectively.

Combination therapy resulted in the largest reduction in liver fat and stiffness among treatment groups. Participants experiencing a relative reduction ≥ 30% or an absolute reduction ≥ 5% in liver fat were the most prevalent in the combination group (100.0% vs. 57.1% in PIO and 87.5% in EMPA, p = 0.010). In addition, the combination group showed the highest proportion of individuals with a relative reduction ≥ 30% in liver fat and ≥ 20% in liver stiffness than the monotherapy groups (50.0% vs. 21.4% in PIO and 6.3% in EMPA, p = 0.029). Combination therapy did not induce the changes in subcutaneous fat deposition observed in the monotherapy groups, but it did show the most substantial reduction in visceral fat, concurrently showing the largest increase in adiponectin level across the three groups (p = 0.036).

Combination therapy of PIO with EMPA showed synergistic benefits for MASLD in individuals with type 2 diabetes, compensating for the inadequate or unfavorable effects of monotherapies; ClincialTrials.gov number, NCT03646292.

The trial was registered at ClinicalTrials.gov (registration number: NCT03646292).

Obesity rates have surged since 1990 worldwide. This rise is paralleled by increases in pathological processes affecting organs such as the heart, liver, and kidneys, here termed systemic metabolic disorders (SMDs). For clinical management of SMD, the European Atherosclerosis Society proposes a pathophysiology-based system comprising three stages: Stage 1, where metabolic abnormalities such as dysfunctional adiposity and dyslipidaemia occur without detectable organ damage; Stage 2, which involves early organ damage manifested as Type 2 diabetes, asymptomatic diastolic dysfunction, metabolic-associated steatohepatitis (MASH), and chronic kidney disease (CKD); and Stage 3, characterized by more advanced organ damage affecting multiple organs. Various forms of high-risk obesity, driven by maintained positive energy balance, are the most common cause of SMD, leading to ectopic lipid accumulation and insulin resistance. This progression affects various organs, promoting comorbidities such as hypertension and atherogenic dyslipidaemia. Genetic factors influence SMD susceptibility, and ethnic disparities in SMD are attributable to genetic and socioeconomic factors. Key SMD features include insulin resistance, inflammation, pre-diabetes, Type 2 diabetes, MASH, hypertension, CKD, atherogenic dyslipidaemia, and heart failure. Management strategies involve lifestyle changes, pharmacotherapy, and metabolic surgery in severe cases, with emerging treatments focusing on genetic approaches. The staging system provides a structured approach to understanding and addressing the multi-faceted nature of SMD, which is crucial for improving health outcomes. Categorization of SMD abnormalities by presence and progression is aimed to improve awareness of a multi-system trait and encourage a tailored and global approach to treatment, ultimately aiming to reduce the burden of obesity-related comorbidities.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most prevalent cause of chronic hepatic disease worldwide. Recently, the association between MASLD and renal injury has emerged as an additional factor impacting the clinical course of MASLD.

The present study evaluated the clinical association in patients with obesity.

This study enrolled patients classified as having obesity class II and III (BMI >35 kg/m2) and MASLD from an obesity surgical treatment center. The diagnosis criteria for MASLD included the presence of hepatic steatosis as indicated by histology or imaging assessments. We use Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NSF) to assess and determine the presence of liver fibrosis. The glomerular filtration rate (GRF) was determined using CKD-EPI (chronic kidney disease epidemiology collaboration) equation, with GFR levels ≥90 and <120 mL/min/1,73 m2 considered within the normal range.

The study comprised a total of 560 individuals with obesity grade II and III, 325 individuals with MASLD. Among these, 422 (75.4%) patients were female, and the mean age was 36±10 years. Systemic arterial hypertension (SAH) was present in 162 (41.1%) patients, and 218 (42.8 %) were diagnosed with type 2 Diabetes Mellitus (T2DM). A total of 286 individuals (51.1%) had a GFR below 114 mL/min, with 183 (64%) of them exhibiting a higher degree of liver fibrosis, as indicated by FIB-4 >0.54.

In patients with obesity classified as grades II and III, age emerged as the primary determinant leading to decline in GFR. Furthermore, glomerular hyperfiltration could be an early sign of progression to chronic kidney disease. Nonetheless, the progression of hepatic fibrosis could also be a significant factor contributing to impaired renal function.

Considering recent revisions in the nomenclature for fatty liver disease, alongside limited data on sex-specific differences in its cardiovascular/mortality outcomes, this study aims to investigate the prevalence and impact of metabolic-associated fatty liver disease (MAFLD) on cardiovascular disease (CVD) and mortality in men and women over a 12-year follow-up period.

In this large population-based cohort study, 7101 individuals aged ≥ 30 were enrolled. The prevalence of MAFLD was investigated in both genders. After excluding individuals with a history of previous CVD, 6331 participants were followed up for CVD and mortality over 12 years. Steatosis was defined as fatty liver index (FLI) ≥ 60. Multivariate-adjusted hazard ratios (HRs) were calculated for CVD and mortality.

The prevalence of MAFLD was 43.2%, higher in men (46.5%) than women (40.6%). Men with MAFLD (47.7 ± 12.1) were younger than women (52.2 ± 11.1). In the 12-year follow-up of 6331 individuals, multivariable-adjusted CVD HRs for MAFLD were 1.36 (1.10-1.67) in men and 1.48 (1.16-1.88) in women. Adjusted mortality HRs were 1.17 (0.86-1.59) and 1.38 (1.00-1.91) in men and women, respectively. Among patients with MAFLD, a subgroup with diabetes faced the highest hazard for CVD and mortality.

This study found that MAFLD is more common in men at a younger age. Despite the higher prevalence in men, women with MAFLD face a greater risk of cardiovascular events and mortality. Findings highlight the importance of gender-specific considerations in primary prevention programmes for MAFLD-related cardiovascular disease and mortality.

The new definition of steatotic liver disease (SLD), as a broader concept, was a step forward in the increasing recognition of the substantial overlap between alcohol and cardiometabolic risk factors (CMRFs), in a continuum way. The spectrum of pathophysiological aspects, ranging from liver steatosis to fibrosis, has similarities in MASLD and ALD. Also, there is now considerable evidence that the association of metabolic dysfunction with increased alcohol consumption impacts on the risk of severe liver disease and prognosis. The new MetALD class, as recently proposed, shows clear differences in prognosis when comparing with MASLD and ALD groups. However, there is room for improvement, such as considering the role of previous alcohol intake, fluctuations of consumption over time, including binge drinking, refinement of alcohol assessment, and better understanding of the role of biomarkers. In summary, SLD is no doubt a significant improvement, but the new classification needs to be dynamic and adapting to patients needing frequent reassessment. Furthermore, it brings opportunities for research on the interaction between alcohol consumption and CMRFs.

Lifestyle-induced weight reduction remains crucial for managing type 2 diabetes and steatotic liver disease, but its effectiveness varies. We postulated that the G allele in the rs738409 single nucleotide polymorphism within patatin-like phospholipase domain-containing protein 3 (PNPLA3), which associates with metabolic dysfunction-associated steatotic liver disease, also modulates diet-related metabolic effects.

Participants with type 2 diabetes were randomized to 8-week hypocaloric diets (energy intake: -1,256 kJ/d of, <30 kcal% fat): high in cereal fiber and coffee excluding red meat (HF-RM + C; n = 16), or low in cereal fiber, devoid of coffee, but high in red meat (LF + RM-C; n = 15). Whole-body insulin sensitivity (M value) was assessed using [2H]glucose and hyperinsulinemic-normoglycemic clamps, hepatic lipid content (HCL) and body fat volumes by magnetic resonance spectroscopy/imaging before and after intervention.

Despite comparable weight loss, HCL decreased more in non-carriers (-65 %) than in G-allele carriers (-36 %) upon HF-RM + C diet (both p < 0.05 vs baseline and between groups), but only among non-carriers (-46 %, p < 0.05 vs baseline) upon LF + RM-C. Upon HF-RM + C diet, increase in insulin sensitivity was not different between carriers (+27 % p = 0.051 from baseline) and non-carriers (+21 %, p = 0.032 from baseline), p > 0.05 for between-group comparison. Upon LF + RM-C diet, both groups equally improved their whole-body insulin sensitivity (+42 % for non-carriers and +37 % for carriers, p < 0.05 vs baseline). Upon HF-RM + C diet, non-carriers decreased circulating interleukin-18 from baseline by -31 %, whereas, upon LF + RM-C diet, non-carriers decreased circulating anti-inflammatory interleukin-1 receptor antagonist levels by 14 % (both p < 0.05 vs baseline).

Humans with the PNPLA3 G-allele show modified dietary-induced effects on steatotic liver disease in type 2 diabetes despite body weight reduction. Registration at Clinicaltrials.gov, Identifier number: NCT01409330.

The Dallas Steatosis Index (DSI) is a non-invasive tool (NIT) developed to detect the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in multi-ethnic populations, external validation in Asians has yet to be conducted. Therefore, we evaluated the ability of the DSI with the BMI classification of WPRO (DSI_WPRO) to identify MASLD in the Chinese population. In addition, we investigated the associations between the DSI_WPRO and the risk of MASLD in a longitudinal study.

Baseline data from the Dongfeng-Tongji cohort were collected to investigate the ability of the DSI_WPRO to identify MASLD patients by ROC analysis. Furthermore, multivariate logistic regressions were performed to investigate the associations of the DSI_WPRO and MASLD risks in a 5-year follow-up of the DFTJ cohort study.

Among a total of 9,376 MASLD participants and 25,974 non-MASLD participants, the area under the curve (AUC) of the DSI_WPRO reached 0.777 after adjusting BMI classification, which is higher than other NITs in this study. In addition, we redefined the risk category and the screening proposal of MASLD in Asians with the DSI_WPRO. We found that the cutoff point of 0 has the best ability to recognize the presence or absence of MASLD. Furthermore, compared with the low DSI_WPRO (DSI_WPRO < 0), OR (95% CIs) of higher DSI_WPRO (DSI_WPRO ≥ 0) was 3.048 (2.827 ~ 3.285) for MASLD.

The DSI is a useful tool for MASLD identification and prevention. After more validation studies, DSI can be generalized in the Asian population.

This study aimed to evaluate the contrast-enhanced ultrasound with Sonazoid (Sonazoid-CEUS) features of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD).

In this retrospective study, patients who underwent surgical resection and were histopathologically diagnosed with NAFLD or cirrhosis-related HCC were included. All patients received Sonazoid-CEUS examinations within 1 week prior to hepatic surgery. The enhancement patterns of HCC lesions were evaluated and compared between the two groups according to the current World Federation for Ultrasound in Medicine and Biology guidelines. Multivariate logistic regression analysis was used to assess the correlations between Sonazoid-CEUS enhancement patterns and clinicopathologic characteristics.

From March 2022 to April 2023, a total of 151 patients with HCC were included, comprising 72 with NAFLD-related HCC and 79 with hepatitis B virus (HBV) cirrhosis-related HCC. On Sonazoid-CEUS, more than half of the NAFLD-related HCCs exhibited relatively early and mild washout within 60 seconds (54.2%, 39/72), whereas most HBV cirrhosis-related HCCs displayed washout between 60 and 120 seconds (46.8%, 37/79) or after 120 seconds (39.2%, 31/79) (P<0.001). In the patients with NAFLD-related HCC, multivariate analysis revealed that international normalized ratio (odds ratio [OR], 0.002; 95% confidence interval [CI], 0.000 to 0.899; P=0.046) and poor tumor differentiation (OR, 21.930; 95% CI, 1.960 to 245.319; P=0.012) were significantly associated with washout occurring within 60 seconds.

Characteristic Sonazoid-CEUS features are useful for diagnosing HCC in patients with NAFLD.

Metabolic dysfunction-associated steatohepatitis (MASH) is associated with a >10-fold increase in liver-related mortality. However, biomarkers predicting both MASH and mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are missing. We developed a metabolome-derived prediction score for MASH and examined whether it predicts mortality in Chinese and European cohorts.

The MASH prediction score was developed using a multi-step machine learning strategy, based on 44 clinical parameters and 250 serum metabolites measured by proton nuclear magnetic resonance in 311 Chinese adults undergoing a liver biopsy. External validation was conducted in a Finnish liver biopsy cohort (n = 305). We investigated associations of the score with all-cause and cause-specific mortality in the population-based Shanghai Changfeng study (n = 5,893) and the UK biobank (n = 111,673).

A total of 24 clinical parameters and 194 serum metabolites were significantly associated with MASH in the Chinese liver biopsy cohort. The final MASH score included BMI, aspartate aminotransferase, tyrosine, and the phospholipid-to-total lipid ratio in VLDL. The score identified patients with MASH with AUROCs of 0.87 (95% CI 0.83-0.91) and 0.81 (95% CI 0.75-0.88) in the Chinese and Finnish cohorts, with high negative predictive values. Participants with a high or intermediate risk of MASH based on the score had a markedly higher risk of MASLD-related mortality than those with a low risk in Chinese (hazard ratio 23.19; 95% CI 4.80-111.97) and European (hazard ratio 20.15; 95% CI 10.95-37.11) individuals after 7.2 and 12.6 years of follow-up, respectively. The MASH prediction score was superior to the Fibrosis-4 index and the NAFLD fibrosis score in predicting MASLD-related mortality.

The metabolome-derived MASH prediction score accurately predicts risk of MASH and MASLD-related mortality in both Chinese and European individuals.

Metabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related death. However, biomarkers predicting not only MASH, but also death due to liver disease, are missing. We established a MASH prediction score based on 44 clinical parameters and 250 serum metabolites using a machine learning strategy. This metabolome-derived MASH prediction score could accurately identify patients with MASH among both Chinese and Finnish individuals, and it was superior to the Fibrosis-4 index and the NAFLD fibrosis score in predicting MASLD-related death in the general population. Thus, the new MASH prediction score is a useful tool for identifying individuals with a markedly increased risk of serious liver-related outcomes among at-risk and general populations.

We aimed to recognize the burden of NAFLD and support public health policy development for its prevention and management.

A cross-sectional analysis of GBD 2021 results was conducted.

We collected incidence data on NAFLD from 1990 to 2021 using Global Burden of Disease Study in 2021. Estimated annual percentage changes (EAPCs) in NAFLD age standardized incidence rate (ASR) were calculated to quantify the temporal trends in NAFLD ASR. Bayesian age-period-cohort models were constructed to project NAFLD incidence rates and cases up to 2050. Additionally, we assessed the percentage of cirrhosis and liver cancer attributable to NAFLD.

Globally, the newly-occurred cases of NAFLD increased by 94.49 % from 24, 856, 159 in 1990 to 48, 353, 272 in 2021. The case number will further increase to 78,602,984 in 2050, and ASR will increase from 5.93 per 1000 in 2021 to 7.26 per 1000 in 2050. The most pronounced increases were observed in young people and men. In 2021, NAFLD accounted for 82.7 % of cirrhosis and other chronic liver diseases and 8.0 % of liver cancer cases.

From 1990 to 2021, the incidence of NAFLD has been continuously increasing and is expected to continue rising until 2050. The increases in young people and men highlight their priority in future schedules. The rising proportions of cirrhosis and liver cancer caused by NAFLD further underscore the serious health risks.

Liver fibrosis has been proposed as the most important predictive indicator affecting prognosis of patients with chronic liver disease. It is defined by an abnormal accumulation of extracellular matrix components that results from necrotic and inflammatory processes and eventually impairs organ function. With no approved therapy, comprehensive cellular models directly derived from patient's cells are necessary to understand the mechanisms behind fibrosis and the response to anti-fibrotic therapies. Primary human cells, human hepatic cell lines and human stem cells-derived hepatic stellate-like cells have been widely used for studying fibrosis pathogenesis. In this paper, we depict the cellular crosstalk and the role of extracellular matrix during fibrosis pathogenesis and summarize different in vitro models from simple monolayers to multicellular 3D cultures used to gain deeper mechanistic understanding of the disease and the therapeutic response, discussing their major advantages and disadvantages for liver fibrosis modelling.

Cardiovascular disease (CVD) is the leading cause of death among patients with non-alcoholic fatty liver disease (NAFLD). This study investigates the association between high-sensitivity cardiac troponin (hs-cTn) levels and mortality in adults at risk of NAFLD in a representative U.S. population sample.

Among participants aged 18 years and older in the 1999-2004 National Health and Nutrition Examination Survey, we measured high-sensitivity troponin T using a single assay (Roche) and high-sensitivity troponin I using three assays (Abbott, Siemens, and Ortho). Myocardial injury was identified by elevated levels of hs-cTn. Mortality outcomes were determined through linkage with the National Death Index database, with follow-up until December 31, 2019. A multivariable Cox proportional hazards model was used to evaluate the associations between myocardial injury and mortality in the NAFLD population. Sensitivity analyses were conducted to assess the robustness of the main findings.

A total of 2581 at risk of NAFLD were included in this observational study, with myocardial injury identified in 7.01%. Over a median follow-up of 16.7 years, 937 all-cause deaths occurred, including 319 cardiovascular disease-related deaths. NAFLD individuals with myocardial injury had worse survival rates at 5, 10, and 15 years compared to those without myocardial injury. After adjusting for baseline characteristics, myocardial injury was associated with an increased risk of all-cause mortality (adjusted Hazard Ratio [aHR] 1.785, 95% CI 1.494-2.134, P < 0.001) and cardiovascular mortality (aHR 2.155, 95% CI 1.606-2.893, P < 0.001).

This large, nationally representative study demonstrates that myocardial injury, defined by elevated hs-cTn levels, is independently associated with increased all-cause and cardiovascular mortality risks in the adult population at risk of NAFLD in the United States. This association persisted after adjusting for various factors and in patients without pre-existing cardiovascular disease. The Siemens hs-cTn I assay demonstrated the strongest association with all-cause mortality. These findings highlight the potential of hs-cTn as a valuable prognostic marker in NAFLD patients, even in those without clinically apparent cardiovascular disease. Routine hs-cTn assessment may aid in risk stratification and guide targeted interventions to reduce mortality risk in this population.

Adult patients with chronic intestinal failure (CIF) may develop intestinal failure-associated steatosis. Asymptomatic steatosis can lead to steatohepatitis and its downstream complications. Monitoring steatosis in daily practice in adult CIF patients is hampered by limited, reliable, accessible, non-invasive methods to measure liver fat content (LFC). Fibroblast growth factor 21 (FGF21) is a hormone that is mainly produced by hepatocytes, and higher plasma levels are associated with the presence and the degree of liver steatosis in several clinical conditions. Furthermore, FGF21 analogues have been shown to reduce fatty liver. FGF21 has previously been suggested as a biomarker for liver steatosis. The aim of this study was to assess the diagnostic performance of FGF21 plasma levels to detect steatosis and steatosis severity in adult CIF patients.

FGF21 plasma levels were quantified using enzyme-linked immunosorbent assay (ELISA) in 48 adult CIF patients who had been receiving home parenteral nutrition (HPN) or intravenous fluids for ≥3 months for ≥2 times per week. Liver fat content (LFC, %) was assessed with proton magnetic resonance spectroscopy (1H-MRS). Patient characteristics of patients with steatosis (LFC >5.5 %) and without steatosis (LFC ≤5.5 %) were compared using the Mann-Whitney U test or Fisher's exact test. The diagnostic value of FGF21 levels to diagnose the presence of steatosis (LFC >5.5 %) was performed by determining the area under the receiver operating characteristics curve (AUC), and the optimal cut-off value was determined. Furthermore, Spearman's rho correlation coefficient was calculated to evaluate the association between FGF21 levels and LFC.

FGF21 plasma levels were measured in 48 patients (median age of 56 years, 71 % female) with a median duration of HPN use of 57 months. Steatosis was diagnosed in 8/48 (17 %) patients, with a median LFC of 8.4 % (range 5.7-39.9 %). CIF patients with steatosis had higher median FGF21 plasma levels (658 pg/mL) than patients without steatosis (299 pg/mL). The area under the curve (AUC) of FGF21 to predict steatosis (LFC >5.5 %) was 0.80 [95 % CI 0.63, 0.96]. With the optimal FGF21 cut-off point at 453 pg/mL, the sensitivity as well as the specificity was 75 %. The calculated Spearman rho correlation found a significant positive correlation (ρ = 0.65, p < 0.001) between FGF21 plasma levels and LFC (%).

Adult CIF patients with steatosis had higher FGF21 plasma levels than CIF patients without steatosis. FGF21 is a good predictor for diagnosing steatosis and has a good correlation with LFC. FGF21 should be considered as a biomarker for steatosis in adult patients with CIF.

To quantitatively assess the fat volume fraction (FVF) in nonalcoholic fatty liver disease (NAFLD) using the spectral computed tomography (CT) multimaterial decomposition (MMD) algorithm and to investigate its association with high-risk coronary plaques (HRP).

This retrospective study included patients diagnosed with coronary artery disease (CAD) from August 2023 to August 2024 who underwent coronary CT angiography and abdominal enhanced spectral CT imaging. Patients were categorised into three groups based on HRP imaging features (positive remodelling, low-density plaques, spotty calcification, and napkin ring sign): no plaque (n = 57), non-HRP (n = 54), and HRP (n = 48) groups. FVF was measured using the spectral CT MMD algorithm to quantify liver fat content. Clinical characteristics, biochemical markers, and imaging differences among the groups were analysed. Univariate and multivariate logistic regression analyses were performed to determine the association between FVF and HRP.

FVF values were significantly higher in the HRP group (13.2%) compared to the non-HRP group (9.2%) and the no plaque group (6.5%) (P<0.001). Multivariate binary logistic regression analysis identified FVF as an independent risk factor for HRP (odds ratio [OR]: 2.55, P<0.001), along with high-sensitivity C-reactive protein (hs-CRP) (OR: 1.94, P=0.025) and diabetes mellitus (OR: 9.83, P=0.002). Additionally, FVF correlated epicardial and pericoronary adipose tissue (PCAT) volume and CT attenuation (P<0.001).

The spectral CT MMD algorithm enables quantitative assessment of FVF, which is independently associated with coronary HRP formation in NAFLD patients. Elevated FVF serves as a risk factor for CAD in patients with NAFLD.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in inflammatory bowel disease (IBD) patients due to chronic inflammation and metabolic disturbances. However, reliable non-invasive biomarkers for MASLD prediction in this population are lacking. This study evaluated the predictive value of metabolic scores and lipid ratios for MASLD onset in IBD patients. Methods: An observational retrospective study was conducted on 358 IBD patients at the "Renato Dulbecco" Teaching Hospital in Catanzaro, Italy, in a period between 1 January 2021 and 31 December 2024. Clinical and laboratory data, including metabolic scores and lipid ratios, were analyzed using the chi-square and Kruskal-Wallis tests as appropriate. Post hoc comparisons were conducted using Dunn's test. Receiver operating characteristic analysis assessed their predictive accuracy for MASLD. p < 0.05 was considered significant. Results: IBD-MASLD patients had a significantly higher body mass index (BMI, 27 ± 4 vs. 22 ± 2 kg/m2; p < 0.001), waist circumference (100 ± 11 vs. 85 ± 4 cm; p < 0.001), other anthropometric parameters, metabolic scores, and lipid ratios than IBD-only patients. The metabolic score for insulin resistance [METS-IR, area under curve (AUC = 0.754)] and waist circumference (AUC = 0.754) exhibited the highest predictive accuracy, followed by the lipid accumulation product (LAP, AUC = 0.737), BMI (AUC = 0.709), and triglyceride/high-density lipoprotein (TG/HDL, AUC = 0.701). Insulin resistance scores, including the homeostasis model assessment of insulin resistance (AUC = 0.680) and triglyceride-glucose index (AUC = 0.674), were of moderate predictive use. The visceral adiposity index (AUC = 0.664) and low-density lipoprotein/high-density lipoprotein (AUC = 0.656) showed lower discriminative ability, while the fibrosis-4 index (AUC = 0.562) had the weakest diagnostic performance. Conclusions: Our findings suggest that MASLD in IBD is primarily driven by cardiometabolic dysfunction. The introduction of the METS-IR, LAP, and TG/HDL into clinical assessments of IBD patients could prove useful in preventing liver and cardiovascular complications in this setting.

Diet, specifically meat consumption, has been implicated as a modifiable risk factor in the development of metabolic-associated fatty liver disease (MAFLD). This study aimed to investigate the associations between various types of meat intake and the risk of severe MAFLD and to examine whether genetic risk influences these associations.

This research utilized data from the UK Biobank, which initially enrolled over 500,000 participants between 2006 and 2010, of whom 487,875 were eligible for our analyses. Meat intake, including unprocessed red meat, processed meat, poultry, and fish, was evaluated through a validated touchscreen questionnaire. Cox proportional hazards models were used to analyze the relationship between meat consumption and severe MAFLD risk, adjusting for potential confounders. Genetic risk scores (GRS) were calculated using five MAFLD-associated SNPs, allowing for analyses of gene-diet interactions.

During a follow-up period totaling 6,036,554 person-years (mean duration: 12.1 years), 5,731 new cases of severe MAFLD were identified. High intakes of total meat, processed meat, unprocessed red meat and poultry were associated with increased MAFLD risk, with adjusted hazard ratios (HR) of 1.76 (95% CI: 1.33-2.33), 1.19 (1.02-1.40), 1.34 (1.17-1.53), and 1.21 (0.98-1.49), respectively, for the highest versus lowest intake categories. In contrast, oily fish intake showed a protective association (HR: 0.72; 95% CI: 0.53-0.97). No significant interaction was observed between meat intake and GRS for any meat subtype, suggesting that the associations were independent of genetic predisposition.

High consumption of red and processed meat was associated with an increased risk of severe MAFLD, while oily fish intake showed an inverse association with the risk of MAFLD. These effects were consistent across genetic risk levels for MAFLD. Our findings reinforce dietary recommendations to limit red and processed meat and encourage oily fish intake for MAFLD prevention, irrespective of individual genetic risk.

Little is known about modifiable risk factors for young-onset ovarian cancer, except for obesity and nulliparity. We investigated the association between non-alcoholic fatty liver disease (NAFLD) and the risk of young-onset ovarian cancer. A total of 2,376,482 women aged 20-39 years who underwent national health screening under the Korean National Health Insurance Service between 2009 and 2012 were included in this nationwide cohort study and followed-up until December 2022. The fatty liver index was used as a diagnostic biomarker for NAFLD. The risk was estimated using multivariable Cox proportional hazards models after adjusting for potential confounders. During 26.8 million person-years of follow-up (median: 11.5 years), 6,319 young women were newly diagnosed with young-onset ovarian cancer. The cumulative incidence probability was significantly higher for those with NAFLD than for those without (log-rank P < 0.01). NAFLD was associated with an increased risk of young-onset ovarian cancer (adjusted hazard ratio [aHR], 95% confidence interval [CI]: 1.30, 1.16-1.45). As the severity of NAFLD increased, the risk of young-onset ovarian cancer tended to increase (aHR, 95% CI: Moderate and severe NAFLD; 1.26, 1.12-1.41 and 1.45, 1.22-1.72, respectively; P for trend < 0.01). NAFLD was independently associated with an increased risk of young-onset ovarian cancer. As NAFLD is modifiable, our findings may benefit the next generation by reducing premature morbidity and mortality associated with young-onset ovarian cancer.

Studies in heterogeneous groups of people with respect to sex, body mass index (BMI), and glycemic status (normoglycemia, impaired glucose tolerance, diabetes), indicate no relationship between liver fat accumulation and pancreatic insulin secretion.

This work aimed to better understand the association of liver fat with insulin secretion.

A cross-sectional analysis was conducted of 61 men with abdominal obesity who had high liver fat (HLF, ≥ 5.6% by magnetic resonance spectroscopy, n = 28) or low liver fat (LLF, n = 33), but were balanced on BMI, total body fat, visceral adipose tissue (VAT), and pancreatic fat. A frequently sampled 5-hour oral glucose tolerance test with 11 samples, in conjunction with mathematical modeling, was used to compute indices of insulin sensitivity and insulin secretion (oral minimal model).

Compared to individuals with LLF, those with HLF had significantly greater fasting glucose, insulin, C-peptide, and triglycerides; lower high-density lipoprotein cholesterol; but similar glycated hemoglobin A1c. Areas under the 5-hour curve for glucose, insulin, and C-peptide were greater in the HLF group than the LLF group (by ∼10%, ∼38%, and ∼28%, respectively); fasting and total postprandial insulin secretion rates were approximately 37% and approximately 50% greater, respectively (all P < .05); whereas the insulinogenic index was not different. HLF participants had lower whole-body and hepatic insulin sensitivity, disposition index, and total insulin clearance than LLF participants (all P < .05).

Accumulation of liver fat is associated with increased insulin secretion independently of total adiposity, abdominal fat distribution, and pancreatic fat. Thereby, hyperinsulinemia in fatty liver disease is partly because of insulin hypersecretion and partly because of impaired insulin clearance.