Predicting disease progression in metabolic dysfunction-associated steatotic liver disease (MASLD) is challenging, and current non-invasive tests (NITs) lack the precision to replace liver biopsy. This study aimed to identify plasma biomarkers for different stages of fibrosis using affinity-based proteomics in two biopsy-proven cohorts. The primary objective was to identify biomarkers capable of distinguishing between low-to-no fibrosis (F0-1) and significant fibrosis (F2-4) in MASLD.

Participants in the discovery cohort were recruited from Uppsala University Hospital and Swedish CArdioPulmonary bioImage Study (SCAPIS), while the validation cohort was included from Linköping University Hospital. All participants diagnosed with MASLD underwent liver biopsy and were categorized by fibrosis stage (F0-1 or F2-4). A total of 276 plasma proteins were analyzed using Olink® panels, with biomarkers identified through ordinal logistic regression, random forest (RF) analysis and the Boruta algorithm.

The discovery cohort included 60 participants, with 60% having fibrosis stage F0-1 and 40% having F2-4. The validation cohort had 59 participants, of whom 35 had fibrosis stage F0-1 (59.3%) and 24 had stage F2-4 (40.7%). Five biomarkers were significantly associated with fibrosis stage in the discovery cohort, with four confirmed in the validation cohort. A model combining angiotensin converting enzyme-2 (ACE2), hepatocyte growth factor (HGF) and insulin-like growth factor-binding protein-7 (IGFBP-7) demonstrated strong predictive performance for significant fibrosis (c-statistics 0.82-0.83), outperforming fibrosis-4 (FIB-4) (c-statistics 0.61-0.72).

A biomarker model including ACE2, HGF and IGFBP7 shows promise in distinguishing between low-stage and significant fibrosis.

In metabolic dysfunction-associated steatotic liver disease (MASLD) and in MASLD with alcohol consumption (MetALD), we investigated the effect of severity of metabolic dysfunction on incident major adverse liver outcomes (MALO), major cardiovascular events (MACE), obesity-related cancers, and all-cause mortality (ACM).

SLD was identified among 502,381 UK Biobank participants using the Hepatic Steatosis Index (HSI) (>36 vs.<30). Metabolic syndrome (MetS) traits and MetS (≥3 traits) using MASLD/MetALD criteria. Cox regression was used to estimate adjusted hazard ratios and 95%CIs [aHR(95%CIs)] of MASLD or MetALD plus 1 to 5 MetS traits with incident MALO, MACE, obesity-related cancers and 5-year/10-year incidence rates versus reference (no SLD/MetS traits).

Median follow-up was 148 to 149 months. Comparing MASLD with one versus five MetS traits, respectively, to the reference; for MALO, [aHRs (95%CIs)] were 2.27 (1.03-5.00) and 9.19 (4.98-16.95); for MetALD, aHRs were 1.65 (0.53-5.11) and 8.54 (3.65-19.95) respectively. For MACE, with MASLD; aHRs were 1.51 (1.19-1.92) and 4.81 (4.06-5.69) respectively; with MetALD, aHRs were 1.46 (1.00-2.13) and 4.64 (3.51-6.14) respectively. For obesity-related cancers; with MASLD, aHRs were 1.04 (0.87-1.23) and 1.46 (1.29-1.66) respectively; with MetALD, aHRs were 1.01 (0.79-1.29) and 1.51 (1.24-1.83) respectively. 5-year and 10-year incidence rates also increased progressively with increasing MetS traits. Combining SLD, MetS and high liver fibrosis risk (defined by FIB-4 ≥ 2.67) was strongly associated with MALO in both MASLD and MetALD (aHRs 27.48, (17.72-42.61); 43.36, 20.53-91.58 respectively).

In MASLD or MetALD, the numbers of MetS traits markedly influence risk and incidence of liver-related outcomes, MACE, obesity-related cancers and ACM.

Our objective was to compare the clinical features of Metabolic dysfunction-associated steatotic liver disease (MASLD) /metabolic alcohol-related liver disease (MetALD)/metabolic associated fatty liver disease (MAFLD)/nonalcoholic fatty liver disease (NAFLD) and the relative risk analysis of metabolic disorders.

The National Health and Nutrition Examination Survey for the 2017-2018 cycle was used to screen the participants. Multivariate-adjusted logistic regression models were applied to explore the difference in relative risk analysis between NAFLD/MAFLD/MASLD/MetALD and metabolic disorders.

Among the 1,862 eligible individuals, 358(44.84%) had MASLD, 213(11.44%) had MetALD, 841(45.17%) had MAFLD, and 1,125(60.42%) had NAFLD. Positive associations with the risk of hypertension were discovered for MASLD (OR = 2.892, 95%CI = 2.226-3.756), MetALD (OR = 1.802, 95% CI = 1.355-2.398), MAFLD (OR = 3.455, 95%CI = 2.741-4.354) and NAFLD (OR = 1.983, 95%CI = 1.584-2.484). Positive associations with the risk of T2DM were discovered for MASLD (OR = 6.360, 95%CI = 4.440-9.109), MAFLD (OR = 7.026, 95%CI = 4.893-10.090) and NAFLD (OR = 3.372, 95%CI = 2.511-4.528). We discovered similar results for hyperlipidemia. Compared to mild steatosis, moderate to severe steatosis in patients with MASLD (OR = 3.924, 95%CI = 2.399-6.419), MAFLD (OR = 3.814, 95%CI = 2.367-6.144), NAFLD (OR = 4.910, 95%CI = 2.983-8.080) has a higher risk for T2DM.

The proposed definitions of MASLD and MetALD are valuable and deserve further exploration. Our findings suggest that MAFLD is a more effective indicator for identifying patients at increased risk for metabolic disorders.

Nonalcoholic fatty liver disease (NAFLD) is characterized by increased lipid accumulation and excessive deposition of extracellular matrix (ECM) that results in tissue stiffening. The potential interplay between matrix stiffness and hepatocyte lipid accumulation during NAFLD has not been established. Here, an in vitro NAFLD model is developed using chemically defined, engineered hydrogels and human induced pluripotent stem cell-derived hepatic organoids (HOs). Specifically, dynamic covalent chemistry crosslinking, along with transient small molecule competitors, are used to create dynamic stiffening hydrogels that enable the reproducible culture of HOs. Within matrices that mimic the stiffness of healthy to diseased tissue (≈1-6 kPa), lipid droplet accumulation in HOs is triggered by exposure to an NAFLD-associated free fatty acid. These NAFLD model suggests that higher stiffness microenvironments result in increased hepatic lipid droplet accumulation, increased expression of fibrosis markers, and increased metabolic dysregulation. By targeting the ROCK mechanosignaling pathway, the synergy between matrix stiffness and lipid droplet accumulation is disrupted. The in vitro model of NAFLD has the potential to understand the role of mechanosignaling in disease progression and identify new pathways for therapeutic intervention.

This study aimed to develop and validate a non-invasive model for screening advanced liver fibrosis and predicting liver-related outcomes in patients with type 2 diabetes mellitus (T2DM).

This study included patients with T2DM from five tertiary hospitals for the development and internal validation of a non-invasive model. Advanced liver fibrosis was defined as a liver stiffness measurement ≥12 kPa. An external validation cohort was obtained from the National Health and Nutrition Examination Survey (NHANES), and the model's predictive performance for hepatocellular carcinoma (HCC) and liver-related mortality was assessed in the UK Biobank.

In total, 28,197 patients with T2DM were enrolled. In the derivation cohort (n = 1,129), waist circumference, alanine aminotransferase, aspartate aminotransferase, platelet count, and albumin were identified as independent risk factors for advanced fibrosis and were fit to develop the "DiabetesLiver score." The area under the curve (AUC) was 0.835 (95% confidence interval [CI]: 0.781-0.890), significantly higher than the AUCs of non-invasive tests (all p < 0.01). It maintained high AUCs of 0.870 and 0.823 in the internal validation (n = 1,000), and NHANES cross-sectional (n = 1,432) cohorts, respectively. A dual cutoff of 2.39 and 3.99 with sensitivity ≥90% and specificity ≥90%, respectively, was used to classify patients into low-, middle-, and high-risk groups. In the UK Biobank cohort (n = 24,636), the high-risk group had an elevated risk of liver-related outcomes.

The DiabetesLiver score demonstrated good performance in identifying advanced liver fibrosis and the development of liver-related events in the T2DM population.

National Natural Science Foundation.

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.

Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide. This study aimed to analyze the risk factors associated with NAFLD progression by collecting and evaluating clinical data of NAFLD patients, providing a scientific basis for its prevention and treatment.

Clinical data of NAFLD patients from June 2015 to June 2016 were retrospectively collected, including gender, age, alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP),γ-glutamyltranspeptidase (GGT), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), fasting blood glucose (FBG), and visceral fat area (VFA). All patients were stratified by gender and age, and logistic regression analysis was used to explore the risk factors for NAFLD disease progression.

ALT, TG, FBG, and VFA were identified as independent risk factors for NAFLD progression. Stratified analysis showed that in male patients, ALT, TG, and VFA were independent risk factors, whereas in female patients, TG, FBG, and VFA were identified as independent risk factors. Age-stratified analysis revealed that ALT, TG, and VFA were significant risk factors for progression in young and middle-aged patients. At the same time, age, ALT, TG, and FBG were substantial in elderly patients.

Different risk factors should be closely monitored in sex- and age-specific populations to prevent NAFLD progression effectively.

Μetabolic dysfunction-associated steatotic liver disease (MASLD) comprises a heterogeneous condition in the presence of steatotic liver. There can be a hierarchy of metabolic risk factors contributing to the severity of metabolic dysfunction and, thereby, the associated risk of both liver and extrahepatic outcomes, but the precise ranking and combination of metabolic syndrome (MetS) traits that convey the highest risk of major adverse liver outcomes and extrahepatic disease complications remains uncertain. Insulin resistance, low-grade inflammation, atherogenic dyslipidaemia and hypertension are key to the mechanisms of liver and extrahepatic complications. The liver is pivotal in MetS progression as it regulates lipoprotein metabolism and secretes substances that affect insulin sensitivity and inflammation. MASLD affects the kidneys, heart and the vascular system, contributing to hypertension and oxidative stress. To address the global health burden of MASLD, intensified by obesity and type 2 diabetes mellitus epidemics, a holistic, multidisciplinary approach is essential. This approach should focus on both liver disease management and cardiometabolic risk factors. This Review examines the link between metabolic dysfunction and liver dysfunction and extrahepatic disease outcomes, the diverse mechanisms in MASLD due to metabolic dysfunction, and a comprehensive, personalized management model for patients with MASLD.

Recent advancements in plasma lipidomes genome-wide association studies data have enhanced our understanding of lipid categories, significantly improving risk assessments for metabolic dysfunction-associated fatty liver disease (MAFLD) beyond traditional lipid biomarkers.

This study utilized Mendelian randomization (MR) to assess the causal relationships between 179 lipid species across 13 subclasses and MAFLD, primarily using the Wald ratio and IVW methods. Corrections were made using false discovery rate (FDR), supplemented by Bayesian colocalization analysis.

Elevated levels of genetically predicted phosphatidylcholine (16:0_16:1) [ORWald ratio = 2.638, 95% CI 1.557-4.469, P = 3.11 × 10-4], phosphatidylcholine (16:1_18:0) (ORWald ratio = 2.644, 95% CI 1.559-4.486, P = 3.11 × 10-4), triacylglycerol (46:2) (ORWald ratio = 2.515, 95% CI 1.524-4.153, P = 3.11 × 10-4), and triacylglycerol (48:2) (ORIVW = 1.863, 95% CI 1.300-2.669, P = 6.95 × 10-4) were significantly associated with increased MAFLD risk, with rs1260326 within the GCKR gene playing a crucial role. Colocalization analysis indicated that in significant evidences, the posterior probability for hypothesis 4 was over 80%, identifying rs780093 as a shared causal variant. Additionally, 16 suggestive evidences were identified.

The study confirmed the significant role of specific lipid molecules in influencing MAFLD risk, providing new scientific bases and potential therapeutic targets for future treatment strategies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, but its pathogenesis is unclear. Here we focus on histidine triad nucleotide-binding protein 2 (HINT2), which is expressed in the mitochondria and is involved in hepatic lipid metabolism and mitochondrial protein acetylation. The expression of HINT2 is downregulated in MASLD. HINT2 inhibits free fatty acid-induced lipid accumulation and impairs mitochondrial function in hepatocytes. Hint2 knockout exacerbates diet-induced hepatic steatosis, inflammation, fibrosis and mitochondrial damage in mice. The overexpression of Hint2 attenuates these alterations. Mechanistically, HINT2 regulates mitochondrial protein acetylation via SIRT3; HINT2 enhances the NAD+-dependent activation of sirtuin-3 (SIRT3) by promoting the mitochondrial influx of NAD+ through solute carrier family 25 member 51 (SLC25A51), thus ameliorating MASLD. Moreover, the downregulation of HINT2 in MASLD is due to YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated regulation. Our results suggest that HINT2 may be an important therapeutic target for MASLD.

The relationship between serum aspartate/alanine aminotransferase ratio (AST/ALT) and subsequent development of chronic kidney disease (CKD) in non-diabetic Asian adults has not yet been fully investigated in longitudinal studies.

The study included all middle-aged and older non-diabetic Japanese citizens who received health check-ups in Zentsuji, Kagawa, Japan (1998-2023). AST/ALT was classified into three categories: < 1.0 (reference), 1.0- < 1.5, and ≥ 1.5. CKD was defined as an estimated glomerular filtration rate of < 60 mL/min/1.73 m2. The Weibull accelerated failure time model was used to examine the association between AST/ALT categories and subsequent CKD onset because the proportional hazards assumption was violated.

Of 6309 men and 9192 women, 2966 men and 4395 women remained in the final cohort. After a mean follow-up of 7.50 years for men and 8.34 years for women, 33.7% of men and 34.0% of women developed CKD. Women had higher AST/ALT than men. In women, a dose-response relationship was observed, with a 9% shorter survival time to CKD onset for AST/ALT ≥ 1.5 compared with AST/ALT < 1.0. In contrast, men had a shorter survival time to CKD onset by point estimates, but the 95% confidence intervals crossed 1 in all models.

In this study comparing the risks of CKD development in non-diabetic men and women by AST/ALT levels, a dose-response relationship was only observed in women. Differences in the distribution of AST/ALT by sex may have affected the results. Therefore, in non-diabetic Japanese women, AST/ALT may be used as an indicator of future CKD development.

Objective: Our study aims to develop a personalized nomogram model for predicting the risk of nonalcoholic fatty liver disease (NAFLD) in hypertension (HTN) patients and further validate its effectiveness. Methods: A total of 1250 hypertensive (HTN) patients from Guangxi, China, were divided into a training group (875 patients, 70%) and a validation set (375 patients, 30%). LASSO regression, in combination with univariate and multivariate logistic regression analyses, was used to identify predictive factors associated with nonalcoholic fatty liver disease (NAFLD) in HTN patients within the training set. Subsequently, the performance of an NAFLD nomogram prediction model was evaluated in the separate validation group, including assessments of differentiation ability, calibration performance, and clinical applicability. This was carried out using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The risk-prediction model for the HTN patients concomitant with NAFLD included oral antidiabetic drugs (OADs) (OR = 2.553, 95% CI: 1.368-4.763), antihypertensives (AHs) (OR = 7.303, 95% CI: 4.168-12.794), body mass index (BMI) (OR = 1.145, 95% CI: 1.084-1.209), blood urea nitrogen (BUN) (OR = 0.924, 95% CI: 0.860-0.992), triglycerides (TGs) (OR = 1.474, 95% CI: 1.201-1.809), aspartate aminotransferase (AST) (OR = 1.061, 95% CI: 1.018-1.105), and AST/ALT ratio (AAR) (OR = 0.249, 95% CI: 0.121-0.514) as significant predictors. The AUC of the NAFLD risk-prediction model in the training set and the validation set were 0.816 (95% CI: 0.785-0.847) and 0.794 (95% CI: 0.746-0.842), respectively. The Hosmer-Lemeshow test showed that the model has a good goodness-of-fit (p-values were 0.612 and 0.221). DCA suggested the net benefit of using a nomogram to predict the risk of HTN patients concomitant with NAFLD is higher. These results suggested that the model showed moderate predictive ability and good calibration. Conclusions: BMI, OADs, AHs, BUN, TGs, AST, and AAR were independent influencing factors of HTN combined with NAFLD, and the risk prediction model constructed based on this could help to identify the high-risk group of HTN combined with NAFLD at an early stage and guide the development of interventions. Larger cohorts with multiethnic populations are essential to verify our findings.

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is a growing global concern. This study assessed the frequency of hepatic steatosis and MAFLD, alongside their associated risk factors, among medical students at Suez University, Egypt. A cross-sectional study was conducted from November 2022 to April 2023 among 84 medical students aged ≥ 18 years. Data on anthropometric parameters, body composition, and lifestyle were collected through self-administered questionnaires, InBody analysis, and FibroScan. MAFLD diagnosis required steatosis (≥ 238 dB/m) with obesity, metabolic dysfunction, or both. Statistical analyses included chi-square tests, ANOVA, and logistic regression. Hepatic steatosis was present in 25% of participants, while MAFLD frequency was 13.1%. Participants with MAFLD exhibited higher body weight (82.34 ± 10.78 kg vs. 65.84 ± 10.61 kg, p < 0.001), BMI (29.05 ± 3.66 vs. 22.90 ± 3.23 kg/m2, p < 0.001), waist circumference (88.73 ± 8.73 cm vs. 78.10 ± 7.96 cm, p < 0.001), BMR (1566.09 ± 27.37 vs. 1429.86 ± 93.44 kcal/day, p < 0.001), and fat mass (32.74 ± 7.25% vs. 23.91 ± 8.60%, p < 0.001). Binary regression analysis revealed increased body weight, BMI, waist circumference, and BMR as significant risk factors for MAFLD. An elevated fat mass percentage with a reduced muscle mass percentage highlighted the sarcopenic obesity role in MAFLD progression. Extreme weight reduction can exacerbate hepatic fat accumulation. Poor sleep quality, a sedentary lifestyle, and an unhealthy diet are also significant predictors. The widespread frequency of steatosis and MAFLD highlights the pressing need to tackle this silent epidemic among young Egyptian adults.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is associated with prevalent cardiovascular disease. More favorable cardiovascular health (CVH) profiles are associated with a lower prevalence of MASLD in cross-sectional studies. The relationship between long-term CVH patterns and MASLD prevalence in midlife remains unknown.

Participants (aged 18-30 years at baseline) of the CARDIA (Coronary Artery Risk Development in Young Adults) study who had individual CVH components measured at 7 examinations over 20 years and liver fat assessed by noncontrast computed tomography at year 25 follow-up were included. CVH score was defined using published American Heart Association definitions. Group-based trajectory modeling was used to identify CVH trajectories. MASLD was defined as liver attenuation of ≤51 Hounsfield units with at least 1 metabolic risk factor after excluding other causes of liver fat. Logistic regression was used to examine associations of CVH trajectory groups and MASLD prevalence. At baseline, 39% of 2529 participants had high and 5% had low CVH, respectively. MASLD prevalence at year 25 was 23% (n=587). Five distinct CVH trajectories were identified. Between the 2 groups that started at similar CVH scores, those whose CVH declined over time had a higher prevalence of MASLD at year 25 (7.0% in high-stable versus 23.0% high-decreasing; 24.4% in moderate-stable versus 35.7% in moderate-decreasing). Lower and decreasing trajectories were associated with higher year-25 MASLD prevalence compared with the high-stable trajectory.

Achieving and maintaining high CVH scores starting in young adulthood lowers the risk of prevalent MASLD in midlife.

Metabolic hepatic steatosis (MetHS) is a clinically heterogeneous, multisystemic, dynamic, and complex disease, whose progression is one of the main causes of cirrhosis and hepatocarcinoma. This clinical practice guideline aims to respond to its main challenges, both in terms of disease burden and complexity. To this end, recommendations have been proposed to experts through the Delphi method. The consensus was optimal in recommendations regarding type 2 diabetes as a risk factor (1.5.1, 4.5.1), in which cases early detection of MetHS should be carried out (4.5.2). Its results also emphasize the importance of the use of non-invasive tests (FIB-4, NFS, HFS) for the exclusion of significant fibrosis in patients with suspected MetHS (2.3.1, 2.3.3). Diagnosis should be carried out through the sequential combination of non-invasive indices and transient elastography by FibroScan® for its risk stratification (2.3.3). A nearly unanimous consensus was reached regarding the role of early prevention in the impact on the quality of life and survival of patients (5.1.2), as well as on the effectiveness of the Mediterranean diet and physical exercise in relation to the improvement of steatosis, steatohepatitis and fibrosis in MetHS patients (5.2.2) and on the positive results offered by resmiterom and semaglutide in promoting fibrosis regression (5.4.1). Finally, a great consensus has been reached regarding the importance of multidisciplinary management in MetHS, for which it is essential to agree on multidisciplinary protocols for referral between levels in each health area (6.2.1), as well as ensuring that referrals to Hepatology/Digestive and Endocrinology or Internal Medicine services are effective and beneficial to prevent the risk of disease progression (6.2.3, 6.3.1).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease influenced by genetic, lifestyle, and environmental factors. While MASLD is more prevalent in men, women are at increased risk after menopause, highlighting the critical pathogenetic role of sex hormones. The complex interplay between estrogen deficiency, visceral fat accumulation, metabolic syndrome (MetS), and inflammation accelerates disease progression, increases cardiovascular (CV) risk, and triggers a cycle of worsening adiposity, metabolic dysfunction, and psychological problems, including eating disorders. Weight loss in postmenopausal women can significantly improve both metabolic and psychological outcomes, helping to prevent MASLD and related conditions. This review examines the prevalence of MASLD, its comorbidities (type 2 diabetes T2D, CV, mental disorders), pathogenetic mechanisms, and pharmacological treatment with GLP-1 receptor agonists (GLP1-RAs), with a focus on postmenopausal women. Given the use of GLP1-RAs in the treatment of obesity and T2D in MASLD patients, and the increase in MetS and MASLD after menopause, this review analyzes the potential of a stable GLP-1-estrogen conjugate as a therapeutic approach in this subgroup. By combining the synergistic effects of both hormones, this dual agonist has been shown to increase food intake and food reward suppression, resulting in greater weight loss and improved insulin sensitivity, glucose, and lipid metabolism. Therefore, we hypothesize that this pharmacotherapy may provide more targeted therapeutic benefits than either hormone alone by protecting the liver, β-cells, and overall metabolic health. As these effects are only supported by preclinical data, this review highlights the critical need for future research to evaluate and confirm the mechanisms and efficacy in clinical settings, particularly in postmenopausal women.

To determine the frequency and association of hyperuricemia in non-alcoholic fatty liver disease patients.

This retrospective study was conducted at multiple healthcare facilities including Baqai Institute of Diabetology and Endocrinology (BIDE), Fatima Hospital and Imam Clinic over a span of one year (July 2023 to June 2024).This multi-center approach allowed for a comprehensive analysis and ensured diverse participant representation. The study focused on patients over 18 years old with known cases of non-alcoholic fatty liver disease (NAFLD) visiting outpatient departments. Demographic details, co-morbidities, examination findings, and pertinent laboratory tests were systematically documented utilizing a standardized proforma. Additionally, ultrasound reports of liver scans were scrutinized to categorize NAFLD severity into mild, moderate, and severe cases.

In this study of 246 NAFLD patients, severity distribution was 35% mild, 24.4% moderate, and 40.2% severe, with a mean age of 53.1 years and a female majority (52%). Significant associations were found between NAFLD severity and age, gender, blood pressure, tobacco use, diet, and obesity. Biomarker analysis revealed elevated levels in severe NAFLD cases, particularly uric acid (7.63 vs. 6.6 vs. 5.96; P<0.001) and HbA1c (6.77 vs. 6.15 vs. 5.8; P<0.001). Hyperuricemia was significantly associated with NAFLD severity (P: 0.001), with 56.6% of severe cases exhibiting hyperuricemia. Univariate logistic regression identified hypertension, diabetes, obesity, and severe NAFLD as significant factors for hyperuricemia (P: 0.0001).

A significant prevalence of hyperuricemia was noted among NAFLD patients, underscoring the importance of integrating uric acid assessments and appropriate management into NAFLD care protocols.

Nonalcoholic fatty liver disease (NAFLD) is a serious public health problem worldwide. The purpose of this study was to investigate whether Yunnan medicine Jiangzhi ointment (YMJO) can relieve the progression of NAFLD and to elucidate the specific mechanism involved. A NAFLD model was established in high-fat diet (HFD)-induced SD rats and free fatty acid (FFA)-induced BRL 3A cells. The expression of autophagy-related proteins and ferroptosis-related proteins was detected using Western blotting. The histopathological features of the livers of NAFLD rats were evaluated using hematoxylin and eosin (HE) and Oil Red O staining. The results revealed that in a successfully established HFD-induced NAFLD rat model, YMJO alleviated the progression of NAFLD, promoted autophagy, and inhibited ferroptosis. This regulatory mechanism is related to the activation of the AMPK pathway. Further study of the molecular mechanism via cell experiments revealed that YMJO activated FFA-induced liver cell autophagy through the AMPK signaling pathway and inhibited ferroptosis, thus alleviating the development of NAFLD. This study revealed that YMJO promotes phosphorylation by activating the AMPK pathway, enhances autophagy, ameliorates ferroptosis induced by high fat, and alleviates the occurrence and development of NAFLD.

Endocrine multisystem defect polycystic ovary syndrome (PCOS) causes hyperandrogenism and infertility. Half of PCOS women have (non-alcoholic fatty liver disease) NAFLD, which increases metabolic disease risk. We tested decorin's effect on NAFLD and related processes in PCOS. NAFLD+PCOS, PCOS+decorin, and control rats were studied. Decorin was evaluated on NAFLD/PCOS rats. Test group rats received HF for eight weeks to generate NAFLD. The rats got 1 mg/kg letrozole orally daily for 21 days to diagnosis PCOS. Afterward, rats got injectable decorin for 14 days. Body weight, liver weight, liver coefficient Abdominal Circumference (AC) and body mass index (BMI) were determined. Blood triglycerides (TG), total cholesterol, LDL-c, AST, and glucose were measured. The insulin, testosterone, estrogen, LH, and FSH were measured by ELISA. GPx, SOD, MDA, TNF-, and Caspase-3 liver immunohistochemistry were evaluated. NAFLD liver tissues in PCOS models showed biochemical and histological alterations. NAFLD+PCOS raised BMI, AC, liver weight, and coefficient. Blood glucose, insulin resistance, TG, ALT, and AST increased. Lipid abnormalities (TG, cholesterol, LDL-c, and HDL-c), oxidative stress markers (MDA, SOD, and GPx), and liver dysfunction were found. Low serum E2 and high T supported PCO. Decorin reduced model rat BMI, liver weight, coefficient, insulin resistance, TG, ALT, and AST. It reduced liver inflammation, improved liver extract lipids, and normalized MDA, SOD, and GPx. In the model group, decorin lowered serum T, E2, LH, caspase 3, and TNF-alpha. Decorating improved NAFLD/PCOS group liver histology and function. Decorin reduces hepatosteatosis by reducing liver inflammation, oxidative stress, and dyslipidemia.

The effects of metabolic syndrome (MetS), its individual components, and baseline liver histology, on the rates of progression and regression of nonalcoholic fatty liver disease (NAFLD), were evaluated.

We conducted a post hoc analysis of a multicenter prospective cohort study using the noninterventional registry of the Nonalcoholic Steatohepatitis Clinical Research Network (2002-2022). We included patients aged 18 years or older with biopsy-proven NAFLD. Outcomes included progression/regression of histology defined by changes in NAFLD Activity Score, nonalcoholic steatohepatitis, or fibrosis. Crude incidence rates were compared among patients with MetS vs those without using Kaplan-Meier curves and log-rank test. Cox proportional hazard models were used to estimate effects of MetS and its components on the fibrosis progression/regression.

We included 452 patients; the mean age was 51 years, one-third was male, and 85% was White. The median follow-up was 4.3 (range: 1-15.6) years. At baseline, patients with MetS, large waist circumference, and impaired glucose tolerance/diabetes had worse ballooning and fibrosis scores and a higher prevalence of definite nonalcoholic steatohepatitis than those without. MetS was not associated with fibrosis progression or regression. Impaired glucose tolerance/diabetes was associated with a higher risk of fibrosis progression (adjusted hazard ratio = 1.61; 95% confidence interval: 1.11-2.34) whereas hypertension was associated with a lower risk (adjusted hazard ratio = 0.64; 95% confidence interval: 0.43-0.96).

In the cohort of patients with NAFLD, MetS was associated with greater histological severity at baseline but was not a risk factor of disease progression or regression. Impaired glucose/diabetes was associated with a higher rate and hypertension with a lower rate of fibrosis progression.

With its increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major global public health concern over the past few decades. Growing evidence has proposed the microbiota-derived metabolites short-chain fatty acids (SCFAs) as a potential factor in the pathophysiology of MASLD and related metabolic conditions, such as obesity and type 2 diabetes mellitus (T2DM). By influencing key pathways involved in energy homeostasis, insulin sensitivity, and inflammation, SCFAs play an important role in gut microbiota composition, intestinal barrier function, immune modulation, and direct metabolic signaling. Furthermore, recent animal and human studies on therapeutic strategies targeting SCFAs demonstrate their potential for treating these metabolic disorders.

Non-alcoholic fatty liver disease (NAFLD) has frequently been associated with obesity, type 2 diabetes (T2D), and dyslipidemia, all of which are shared by increased insulin resistance. It has become the most common liver disorder in Korea as well as in developed countries and is therefore associated with an increased health burden of morbidity and mortality. It has an association with T2D, and T2D increases the risk of cirrhosis and related complications. NAFLD encompasses a disease continuum from simple steatosis to non-alcoholic steatohepatitis which is characterized by faster fibrosis progression. Although its liver-related complication is estimated to be, at most, 10%, it will be a leading cause of cirrhosis and hepatocellular carcinoma soon in Korea. Although the main causes of death in people with NAFLD are cardiovascular disease and extra-hepatic malignancy, advanced liver fibrosis is a key prognostic marker for liver-related outcomes and can be assessed with combinations of non-invasive tests in the community. A number of components of metabolic syndrome involved could be another important prognostic information of NAFLD assessed easily in the routine care of the community. There is a few approved therapies for NAFLD, although several drugs, including antioxidants, attract practitioners' attention. Because of the modest effect of the present therapeutics, let alone complex pathophysiology and substantial heterogeneity of disease phenotypes, combination treatment is a viable option for many patients with NAFLD in the Korean community. Comprehensive approach taking healthy lifestyle and weight reduction into account remain a mainstay to the prevention and treatment of NAFLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of end-stage liver disease. MASLD and liver fibrosis are associated with cardiometabolic risk factors and health-related quality of life (HRQOL) while being affected by dietary/exercise patterns and social determinants of health (SDOH). However, previous studies have not assessed in conjunction exercise, diet, SDOH, and HRQOL in patients with MASLD. This was a cross-sectional study of patients with MASLD seen in hepatology clinic at University of Michigan. Participants completed validated surveys on HRQOL, diet, and physical activity, and a subset also underwent vibration controlled transient elastography (VCTE). The primary outcomes were HRQOL (measured by Short Form-8) and cirrhosis, and predictors were physical activity, dietary patterns, cardiometabolic comorbidities, and social determinants of health. The primary analysis included 304 patients, with median body mass index 32.4 kg/m2 and prevalence of type 2 diabetes, hypertension, and dyslipidemia 38%, 45%, and 42%, respectively (Table 1). The majority of the participants had a FIB-4 score of less than 1.3 and LSM of less than 8 (Table 1). HRQOL was lower with higher BMI, type 2 diabetes, hypertension, and increased liver fibrosis, and higher in people with adequate fruit intake. Neighborhood-level SDOH were also associated with HRQOL. Factors associated with cirrhosis or higher liver stiffness measurement by VCTE included body mass index, diabetes, and living in an impoverished neighborhood, while increased vegetable intake and exercise were associated with lower prevalence of cirrhosis/fibrosis. In multivariable models including demographic and cardiometabolic factors, dietary patterns and SDOH were independently associated with HRQOL and cirrhosis. Cardiometabolic risk factors, physical activity, diet, and social determinants of health are associated with HRQOL and liver fibrosis.

Hepatocellular carcinoma (HCC) is expected to become the third most common cause of cancer death worldwide by 2030. The increase in HCC is in large part due to the rising prevalence of risk factors such as type 2 diabetes mellitus (T2DM). Up to 1 in 20 people living with T2DM have liver cirrhosis, and they have a 1% to 2% incidence of HCC per year. Patients with cirrhosis enter surveillance for HCC to identify early-stage, curable tumours. A diagnosis of T2DM does not mandate testing to identify patients with cirrhosis, with testing restricted to those with additional risks. There has never been a trial and nested cost-effectiveness evaluation comparing screening all patients with T2DM for cirrhosis against usual care.

The study will use a multi-centre, unblinded individual randomised controlled trial design. The aim will be to determine the effectiveness and cost-effectiveness of screening all adults with T2DM to identify those at high risk of HCC. The recruitment strategy has been supported by patient and public involvement (PPI). Participants will be identified via an automated search of primary care records and invited to participate via text. 320 participants will be randomised for screening. The screening will include measurement of bio-markers for liver fibrosis (ELF and Fib-4) and vibration-controlled transient elastography. Another 320 participants will be randomised to standard care. Demographic and medical history data will be collected at baseline from all participants. Outcome data will be collected remotely from healthcare records. The primary outcome is the proportion of participants in each arm who are referred to HCC surveillance following testing for liver disease within 12 months of randomisation. The results will be used to calculate the incremental cost-effectiveness ratio of screening via a Markov model.

The results of this study will be presented directly to National Health Service England. Additional dissemination via conference proceedings and publication will be supported by our PPI team. Ethical approval was granted by the West of Scotland Research Ethics Service on 2 August 2023, REC reference 23/WS/0102.

ISRCTN17017677.

Background/Objectives: VelacurTM is a novel, point-of-care ultrasound device developed to accurately diagnose patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH). The Velacur system non-invasively assesses liver stiffness, attenuation, and the Velacurdetermined fat fraction (VDFF). In this study, the performance of Velacur was measured against biopsy results in a cohort of MASLD and MASH patients. Methods: This prospective study enrolled adult patients who were scheduled to undergo biopsy within 6 months of enrollment. The primary objective was to validate Velacur's findings against that of histological findings. The secondary objective was to compare Velacur results with those of FibroScan. Results: A total of 78 participants were enrolled, and 70 were included in the analysis. Patients had a mean age of 53.3 ± 13.1 years, with a mean BMI of 35.0 ± 6.24 kg/m2. A total of 11, 19, 13, 25, and 2 were characterized as F0 to F4, respectively. The mean Velacur stiffness was 6.48 ± 1.4 kPa, and the mean VDFF was 14.4 ± 5.1%. In patients with significant fibrosis the Velacur AUC [95% CI] was 0.86 [0.76, 0.93] and 0.79 [0.66, 0.88] for patients with advanced fibrosis. For measurements of steatosis, 2, 24, 20, and 24 patients were found to have S0 to S3, respectively. To determine moderate steatosis (≥S2), the VDFF had an AUC of 0.846 [0.716, 0.920]. In the comparison population (n = 59), VDFF (0.85 [0.72, 0.94]) was significantly different than FibroScan CAP (0.50 [0.35, 0.66]) for the detection of moderate steatosis. Conclusions: This study validates the use of Velacur as a non-invasive tool for assessment of steatosis and fibrosis, hallmarks of MASLD and MASH, when compared to histological evidence provided via hepatic biopsy. Further, Velacur outperformed FibroScan in the assessment of steatosis.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by combinations of insulin resistance and insulin deficiency. Non-alcoholic fatty liver disease (NAFLD) is emerging as a public health problem worldwide and affects up to 70% of patients with T2DM. Although patients with T2DM have an increased risk of developing advanced liver disease compared to healthy individuals, varying prevalence rates of NAFLD among patients with T2DM, ranging from 34% to 94%, have been reported.

To determine prevalence and identify associated factors of NAFLD among Limbe patients with T2DM and evaluate correlation with glycemic control.

A cross-sectional study was carried out from February to June 2024 among patients with T2DM. Gamma-glutamyl transferase (GGT) activity and serum triglycerides (TGs) were measured by spectrophotometry. NAFLD was diagnosed using the fatty liver index score. Data were analyzed using SPSS version 26.0 for Windows. Student's t-test was used to compare the means of two groups. The χ 2 test was applied to determine the association of NAFLD and T2DM. Logistic regression analysis was performed to identify predictors of NAFLD. P < 0.05 was considered statistically significant.

Of the 150 patients with T2DM recruited for this study, 63 (58%) were females and the majority (84.7%) had good glycemic control (glycated hemoglobin < 7%). Prevalence of NAFLD among patients with T2DM was 19%. Patients with NAFLD had significantly elevated levels of TGs, GGT, and increased body mass index and waist circumference compared to those without NAFLD. There was a significant association between NAFLD and glycemic control. Predictive factors of NAFLD among patients with T2DM were vegetable intake of less than three times per week [adjusted odds ratio (aOR): 0.131, 95%CI: 0.020-0.839; P = 0.032], central obesity (aOR: 0.167, 95%CI: 0.037-0.748; P = 0.019), and metformin treatment for T2DM (aOR: 0.167, 95%CI: 0.037-0.718; P < 0.001).

The prevalence of NAFLD in patients with T2DM in Limbe Regional Hospital was 19%. Age, central obesity, metformin use, and infrequent consumption of vegetables were important predictors of NAFLD.

Previous studies have shown that methyl tert-butyl ether (MTBE) could interfere with lipid metabolism. However, there is still a lack of epidemiological reports on the association between MTBE exposure and the risk of nonalcoholic fatty liver disease (NAFLD). In this study, a cross-sectional study was performed with data from the 2017-2020 cycles of the National Health and Nutrition Examination Survey (NHANES). The target population consisted of adults with reliable vibration controlled Transient elastography (VCTE) and blood MTBE concentration results. The hepatic steatosis and fibrosis were assessed by the values of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Generalized linear mixed model analysis was performed to evaluate the association between MTBE exposure and both steatosis and early liver fibrosis after adjustment for potential confounders. A total of 1303 subjects were enrolled and divided into NAFLD groups (CAP ≥ 248) and non-NAFLD groups (CAP < 248) based on the values of CAP in this study. Generalized linear mixed analysis suggested that blood MTBE concentration was positively associated with NAFLD risk in whole populations (OR: 2.153, 95% confidence interval [CI], 1.176-3.940) and female populations (OR: 11.019, 95% CI: 2.069-58.676). Blood MTBE concentration still showed an obvious positive correlation with the NAFLD risk after excluding factors such as diet and exercise in whole populations. Similarly, a positive correlation between blood MTBE concentration and liver fibrosis was also observed, although the results did not show significant statistical differences. In conclusion, our results indicate that MTBE exposure might be a potential important environmental pathogenic factor for NAFLD.

Severity of fibrosis is the driver of liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD), and non-invasive testing such as fibrosis-4 (FIB-4) score is utilized for risk stratification. We aimed to determine if primary care patients at risk for MASLD and advanced fibrosis were evaluated with subsequent testing. A secondary aim was to determine if at-risk patients with normal aminotransferases had advanced fibrosis.

Primary care patients at increased risk for MASLD with advanced fibrosis (n = 91,914) were identified using previously established criteria. Patients with known alternative/concomitant etiology of liver disease or cirrhosis were excluded. The study cohort included patients with calculated FIB-4 score in 2020 (n = 52,006), and stratified into low, indeterminate, and high likelihood of advanced fibrosis. Among those at indeterminate/high risk, rates of subsequent testing were measured.

Risk stratification with FIB-4 characterized 77% (n = 40,026) as low risk, 17% (n = 8847) as indeterminate, and 6% (n = 3133) as high risk. Among indeterminate/high-risk patients (n = 11,980), 78.7% (n = 9433) had aminotransferases within normal limits, 0.95% (n = 114) had elastography, and 8.2% (n = 984) were referred for subspecialty evaluation.

In this cohort of primary care patients at risk for MASLD with fibrosis, the FIB-4 score identified a substantial proportion of indeterminate/high-risk patients, the majority of which had normal aminotransferase levels. Low rates of subsequent testing were observed. These data suggest that a majority of patients at increased risk for liver-related outcomes remain unrecognized and highlight opportunities to facilitate their identification.

A bidirectional relationship exists between obstructive sleep apnoea (OSA) and type 2 diabetes (T2D). We aimed to examine the cumulative impact of having both OSA and T2D on patient outcomes, relative to having either condition alone.

Using TriNetX, a global federated research network (n = 128 million), we undertook two retrospective cohort studies, using time-to-event analysis. Analysis 1 compared OSA with T2D versus OSA alone; analysis 2 compared T2D with OSA versus T2D alone. Propensity score matching using greedy nearest neighbour (calliper 0.1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes-related (microvascular) and cancer events over 1-5 years.

Analysis 1 (n = 179 688): A codiagnosis of T2D/OSA significantly increased risk of all-cause mortality (hazard ratio [HR] 1.52; confidence interval [CI]: 1.48, 1.57), dementia (HR 1.19; CI: 1.12, 1.26), liver (HR 2.20; CI: 1.77, 2.73), pancreatic (HR 1.62; CI: 1.35, 1.93), colon, renal and endometrial cancers; all cardiovascular, microvascular and liver related outcomes versus OSA alone over 1-5 5 years following OSA diagnosis. Analysis 2 (n = 240 094): A codiagnosis of OSA/T2D significantly increased the risk of peripheral (HR 1.39; CI: 1.36, 1.43) and autonomic (HR 1.63; CI: 1.51, 1.75) neuropathy; retinopathy (HR 1.13; CI: 1.09, 1.18), CKD (HR 1.21; CI: 1.18, 1.23); all cardiovascular and liver outcomes; all-cause mortality and several obesity related cancers versus T2D alone.

T2D significantly potentiates risk of cardiovascular, malignancy and liver-related outcomes in individuals with OSA. OSA, in individuals with T2D, significantly potentiates risk of cardiovascular disease, malignancy, death and several microvascular complications (retinopathy, CKD, peripheral/autonomic neuropathy).

The study aimed to evaluate blood biochemical markers in individuals with type 2 diabetes (T2D) and liver cirrhosis (LC) to discover if they may be utilized to assess their nutritional status, specifically protein malnutrition (PM). A retrospective examination of 500 T2D patients referred to the hospital from January 2022 to December 2023 was performed. After that, participants were split into 2 groups: LC and non-LC. The research comprised T2D individuals with LC. We used their medical data and referring physician reports. Two hundred thirty-five (47%) individuals diagnosed with both T2D and LC were included in the study out of a total of 500 patients referred to Madinah Hospital. The LC group had greater average age, body mass index (BMI), fasting blood glucose, hemoglobin A1c, insulin resistance, and triglycerides as compared to other T2D patient groups without LC. Two hundred thirty-five people with LC were evaluated nutritionally using biomarkers including total protein, albumin, urea, creatinine, and transferrin, which can be a useful evaluation method. A 53.2% of individuals with LC and T2D had PM. A 47% of 500 individuals with T2D and LC. LC had elevated levels of BMI, lipids, liver enzymes, and total bilirubin. A 53.2% had PM as shown by biochemical markers, which might be useful in evaluating patients' nutritional status. PM correlated with older age, decreased hemoglobin levels, reduced total protein, albumin, and transferrin but high ALP with high BMI index (obese). These findings can assist T2D with LC specialists develop better nutritional management and quality of life methods.

The aim of this study was to determine the prevalence of advanced hepatic fibrosis and to individualize using Bayesian analysis its associated risk factors in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) being cared for in three Alsatian cardio-metabolic health networks in the North East of France. Overall, 712 patients aged ≥18 years with a female predominance were included into a prospective, cross-sectional, and observational study. Advanced fibrosis and severe steatosis were evaluated using transient elastography (FibroScan®). The proportion of MASLD patients was 80% and 84% in women and men (difference -4.2% [-10.0; 1.9]), respectively. Advanced fibrosis was observed in 11% of patients, being more common in men (16.9%) than women (7.5%) (difference 9.4 [4.3-15.0]). Severe steatosis was also more common in men (74.9%) than women (63.4%) (difference 11.4 [4.2-18.2]). Only three of the tested variables were likely associated with advanced fibrosis: gender (OR: 1.78 [1.17-2.68]; Pr [OR >1] = 1), T2DM (OR: 1.54 [1-2.37]; Pr [OR >1] = 0.97) and hypertriglyceridemia (OR: 1.49 [0.97-2.27]; Pr (OR >1) = 0.97). In conclusion, this study confirmed the usefulness of assessing hepatic fibrosis in patients with metabolic dysfunction. Therefore, access to FibroScan® should be facilitated in all cardio-metabolic health networks.

Non-alcoholic fatty liver disease (NAFLD) is closely related to type 2 diabetes (T2D), with reduced insulin sensitivity being a key factor in their disrupted metabolic processes. The single point insulin sensitivity estimator (SPISE) is a novel index. This study aims to explore the association between SPISE and NAFLD in T2D population.

This study included a total of 2,459 patients with T2D. SPISE was calculated based on high density lipoprotein-cholesterol (HDL-c), triglycerides (TG), and body mass index (BMI). Participants were categorized into NAFLD and non-NAFLD groups based on the results of ultrasonographic diagnosis. The relationship between SPISE and NAFLD was analyzed separately for each gender.

The overall prevalence of NAFLD is 38.5%. In females and males, the SPISE was significantly reduced in the NAFLD group compared to the non-NAFLD group (both P < 0.05). The prevalence of NAFLD showed a significant reduction across quartiles of the SPISE in both genders (both P < 0.05).Additionally, univariate correlation analysis showed a negative correlation between SPISE and NAFLD (both P < 0.05). In multivariate regression analysis, a reduced SPISE was identified as an independent risk factor for NAFLD (odds ratios of 0.572 and 0.737, 95% CI of 0.477-0.687 and 0.587-0.926, respectively).Moreover, the area under the receiver operating characteristic (ROC) curve for SPISE was 0.209 in females and 0.268 in males (95% CI of 0.175-0.244 and 0.216-0.320, respectively). These results are more meaningful than those of other variables.

SPISE is significantly reduced in NAFLD patients with T2D. Compared to other indicators, SPISE demonstrates superior predictive value in diagnosing NAFLD, and it is independent of gender.

Attenuated insulin-sensitivity (IS) is a characteristic of type 2 diabetes (T2D) and is closely linked to non-alcoholic fatty liver disease (NAFLD). In recent years, many surrogate markers of IS have emerged to predict NAFLD. A natural log transformation of the glucose disposal rate (loge GDR) has been proposed as a new model for IS in patients with T2D. Our aim is to explore the correlation between loge GDR and NAFLD in normoalbuminuric patients with T2D.

A total of 1227 normoalbuminuric patients with T2D were involved in our study. NAFLD was evaluated by ultrasound. Biochemical and clinical data were collected, including parameters essential for calculating the loge GDR (triglycerides, urinary albumin-to-creatinine ratio, γ-glutamyl transferase and body mass index), as well as other relevant covariates required for adjustment. The relationship between the loge GDR and NAFLD was analyzed.

NAFLD patients showed lower loge GDR values than non-NAFLD (P < 0.001). As the loge GDR tertiles increased, the prevalence of NAFLD was decreased (P < 0.001). Multivariate analysis displayed that loge GDR was independently corrected with NAFLD (OR: 0.084; 95% CI: 0.040-0.177). Furthermore, receiver operating characteristic (ROC) analysis showed that loge GDR (area under the curves: 0.797) was superior to other evaluation variables.

The loge GDR was strongly associated with NAFLD and might be a useful predictor in normoalbuminuric patients with T2D.

Non-alcoholic fatty liver disease (NAFLD) is a widespread liver condition associated with diabetes, metabolic syndrome, and cardiovascular diseases, yet public awareness remains low. Early detection of risk factors is crucial, but liver biopsy, the diagnostic gold standard, is invasive and costly. Non-invasive anthropometric indices provide a safer alternative. This study examines these indices to identify the most reliable predictor of NAFLD in adults.

In the present cross-sectional study, we used the Fasa Cohort Data, conducted on about 10,000 people, of whom 1,047 were diagnosed with NAFLD. NAFLD diagnosis in this study was confirmed by physicians based on medical history and ultrasonographic evaluations, ensuring accurate and reliable identification of cases. General, anthropometric, and dietary assessments were performed using interviews, tools, and valid questionnaires. Biochemical evaluation was also done. Waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), Body mass index (BMI), a body shape index (ABSI), body roundness index (BRI), and visceral fat index (VAI) were also calculated using these measurements and formulas. This study used descriptive tests, binary logistic regression, and ROC curve analysis.

In both crude and adjusted models, significant associations were found between WHR, WHtR, BMI, and VAI with NAFLD. ROC analysis revealed that WHtR and BMI were the most accurate predictors of NAFLD in both genders (WHtR: men AUC = 0.750, women AUC = 0.702; BMI: men AUC = 0.754, women AUC = 0.701). BRI showed significant accuracy, but WHR (men: AUC = 0.727, women: AUC = 0.640) and VAI (men: AUC = 0.621, women: AUC = 0.622) were less effective. ABSI demonstrated poor predictive power (men: AUC = 0.530, women: AUC = 0.505) and is not recommended for NAFLD prediction.

Based on the findings, BMI and WHtR emerge as the most practical and accessible indicators for early screening of NAFLD in both men and women, while ABSI shows minor effectiveness in identifying the disease.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is a broad condition characterized by lipid accumulation in the liver tissue, which can progress to fibrosis and cirrhosis if left untreated. Traditionally, liver biopsy is the gold standard for evaluating fibrosis. However, non-invasive biomarkers of liver fibrosis are developed to assess the fibrosis without the risk of biopsy complications. Novel serum biomarkers have emerged as a promising tool for non-invasive assessment of liver fibrosis in MAFLD patients. Several studies have shown that elevated levels of Mac-2 binding protein glycosylation isomer (M2BPGi) are associated with increased liver fibrosis severity in MAFLD patients. This suggests that M2BPGi could serve as a reliable marker for identifying individuals at higher risk of disease progression. Furthermore, the use of M2BPGi offers a non-invasive alternative to liver biopsy, which is invasive and prone to sampling errors. Overall, the usage of M2BPGi in assessing liver fibrosis in MAFLD holds great promise for improving risk stratification and monitoring disease progression in affected individuals. Further research is needed to validate its utility in clinical practice and establish standardized protocols for its implementation.