The LiverRisk score (LRS) has recently been proposed to predict liver fibrosis and future development of liver-related outcomes in the general population. Here, we performed an external validation of this score.

We used data from National Health and Nutrition Examination Survey 2017-2020, a United States population-based cohort to assess the diagnostic accuracy of the LRS to detect a liver stiffness measurement (LSM) ≥8 and ≥12 kPa. Performance was tested among the entire general population and clinically relevant subgroups.

The cohort comprised 7,025 participants (aged 49 [33-63], 49% male), and 9.7% had an LSM ≥8 and 3.2% had an LSM ≥12 kPa. The area under the receiver characteristic operator curve (AUC) in the overall population was 0.73 (95% confidence interval [CI] :0.71-0.75) and 0.78 (95% CI: 0.74-0.81) to detect an LSM ≥8 and ≥ 12 kPa, respectively, significantly outperforming the fibrosis 4 index (FIB-4) but not the nonalcoholic fatty liver disease fibrosis score, steatosis-associated fibrosis estimator (SAFE), or metabolic dysfunction-associated fibrosis 5 (MAF-5). Performance was consistent among most subgroups, but AUC levels to detect an LSM ≥8 kPa decreased to <0.70 among participants aged 18-40 or 60-80 years, blacks, and individuals with diabetes or liver steatosis. The LRS categorized 80.5% as very low risk, 17.7% as low risk, and 1.8% as at risk, prevalence of an LSM ≥8 in these groups was 6.3%, 20.8%, and 50.5%, respectively. The sensitivity to detect an LSM ≥8 kPa was 47.3% in the overall population (but dropped to 21.3% for individuals aged 18-40 years) despite applying the lowest cut-off, which should yield the highest sensitivity.

The LRS score is a promising new tool to predict liver fibrosis; however, its diagnostic accuracy attenuates especially among patients aged 18-40 or 60-80 years. The overall sensitivity was only 47.3% at the lowest LRS cut-off. Further studies assessing cost-benefit ratios according to the LRS compared to FIB-4 and other risk scores such as MAF-5 and SAFE are required to determine its usefulness in referral strategies.

The stress hyperglycemia ratio (SHR) offers a more nuanced understanding of glucose metabolism by factoring in the background glycemia through the component of Hemoglobin A1c. The association of SHR with cardiovascular and cerebrovascular diseases has been established, but the relationship between SHR and the risk of nonalcoholic fatty liver disease (NAFLD) remains unexplored. This study aimed to elucidate the relationship between the two among U.S. adults with diabetes or prediabetes.

A total of 1409 participants diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were included in this study. Multiple logistic regression models (ranging from unadjusted to fully adjusted), restricted cubic splines, and subgroup analyses were employed to determine the relationship between SHR and NAFLD risk and to assess the stability of this relationship across different populations. The average age of all participants was 54.65 years, with males accounting for 47.91 %, and the prevalence of NAFLD being 68.77 %. A fully adjusted logistic regression model indicated a positive association between SHR levels and the risk of NAFLD. Specifically, for each one standard deviation increase in SHR, the risk of NAFLD increased by 20 % (OR, 1.2; 95 % CI, 1.0-1.4). Both the trend test and the restricted cubic splines suggested a linear relationship between the two variables (p for trend <0.05, p for nonlinear = 0.390). Subgroup analysis demonstrated that this positive association remained consistent across most subgroups.

SHR was identified as a valuable index for predicting the risk of NAFLD among U.S. adults with diabetes or prediabetes.

The non-HDL cholesterol to HDL cholesterol ratio (NHHR) is a novel composite lipid index. However, its relationship with mortality, particularly in individuals with non-alcoholic fatty liver disease (NAFLD), remains unclear. The aim of this study was to explore the association between NHHR and both all-cause and cardiovascular mortality in adults with NAFLD in the United States.

This study included 12,648 adult participants with NAFLD from the National Health and Nutrition Examination Survey (NHANES) database (1999-2018). Multivariate Cox proportional hazards models and restricted cubic spline (RCS) methods were employed to assess all-cause and cardiovascular mortality. Subgroup analyses were performed to verify the consistency of these associations.

Over a median follow-up of 99.27 months, 1,659 participants died from all causes, including 460 from cardiovascular disease. RCS analysis revealed a U-shaped relationship between NHHR and all-cause mortality, no association was found between NHHR and cardiovascular mortality. The inflection points for all-cause mortality were 2.67. Subgroup analysis showed that a stronger association between NHHR and all-cause mortality in those with diabetes(P = 0.048).

NHHR is associated with all-cause mortality in NAFLD patients, with distinct non-linear relationships, while it is not associated with cardiovascular mortality. NHHR monitoring may be valuable for assessing mortality risk, particularly in those with diabetes.

Mounting evidence has established metabolic dysfunction-associated steatotic liver disease (MASLD) as an independent risk factor for heart failure (HF), particularly HFpEF. This narrative review explores the impact of MASLD on cardiovascular structure and function. We summarize findings from multiple cohort studies demonstrating that MASLD is associated with distinct patterns of adverse cardiac remodeling, including increased left ventricular concentricity and impaired diastolic function. These subclinical changes in cardiac structure and function often precede overt HF development and appear to occur in the context of multiple interconnected pathways involving metabolic dysfunction, systemic inflammation, adipose tissue dysregulation, vascular dysfunction, and altered hepatic hemodynamics. Early identification of cardiac structural and functional abnormalities through systematic screening may enable timely intervention in this high-risk population. Lifestyle modifications remain foundational, however, achieving and maintaining significant weight loss is challenging. Recent clinical trials have shown promising results with cardiometabolic agents, particularly GLP-1 receptor agonists, which demonstrate significant weight loss and hepatic and cardiovascular benefits. Despite these advances, key knowledge gaps remain regarding optimal screening strategies, mechanisms linking MASLD to HF, and targeted therapeutic approaches. Addressing these gaps will be essential for developing effective prevention and treatment strategies in this high-risk population.

Metabolic-dysfunction associated fatty liver disease (MAFLD) is a widespread chronic liver condition that has been steadily increasing among adolescents and young adults in recent years, posing a major global public health concern. This study aims to conduct an in-depth analysis of the Global Burden of Disease (GBD) 2021 data on MAFLD, focusing on prevalence, incidence, and disability-adjusted life years (DALY) for individuals aged 15-39, spanning the period from 1990 to 2021. This research examines data from the GBD study covering 1990 to 2021 to assess the prevalence, incidence, and DALYs associated with of MAFLD in adolescents and young adults aged 15-39. The analysis is broken down by socioeconomic status, geographic regions, and specific countries. Advanced statistical methods, including the estimated annual percentage change (EAPC) and Bayesian age-period-cohort (BAPC) modeling, were used to deliver the most current and thorough epidemiological assessment of MAFLD in this demographic. In 2021, the estimated global cases of non-alcoholic fatty liver disease among adolescents and young adults reached approximately 423 million, representing a 75.31% increase from 1990. The age-standardized prevalence rate (ASPR) was 14,221.32 cases per 100,000 population, and the age-standardized incidence rate (ASIR) was 977.61 cases per 100,000 population in 2021. Between 1990 and 2021, the ASPR, ASIR, age-standardized DALY rate, and age-standardized mortality rate showed a continuous upward trend, with EAPC of 0.84, 0.79, 0.65, and 0.81, respectively. Regions with Middle and Low-middle Socio-Demographic Index (SDI), as well as High-middle SDI, emerged as "hotspots" for MAFLD prevalence, particularly in North Africa, the Middle East, East Asia, and South Asia. Males exhibited higher prevalence rates compared to females, and the rates continued to increase across all adolescents and young adult age groups. By 2050, the ASPR for MAFLD among this population is projected to reach 16,101 cases per 100,000, signaling an alarming trend. Over the last 30 years, the burden of metabolic-dysfunction associated fatty liver disease has significantly increased among adolescents and young adults worldwide. To counter this rising global health concern, it is crucial to develop and implement targeted and effective interventions tailored to socio-economic settings.

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease characterized by inflammation and fibrosis, with enhanced interleukin-18 (IL-18) signaling. IL-18-binding protein (IL-18BP) neutralizes IL-18, but its therapeutic potential in MASH is unclear. We find elevated IL-18BP and IL-18 levels in patients with MASH and mice, with free IL-18 correlating with disease severity. IL-18 stimulates interferon-gamma (IFNγ) production in CD4 T cells, increasing hepatic IL-18BP. IL-18BP-deficient mice show worsened liver inflammation and fibrosis. We develop a human IL-18BP biologics (APB-R3) and inject it to mice to evaluate its pharmacologic efficacy. APB-R3 significantly improves MASH in reducing fibrosis and inflammation and inhibits hepatic stellate cell activation via the cGMP pathway. This study proposes that abrogation of IL-18 signaling by boosting IL-18BP can strongly inhibit the development of MASH-induced fibrosis, and our engineered IL-18BP biologics can become a promising therapeutic candidate for curing MASH.

The molecular mechanisms underlying metabolic dysfunction-associated steatotic liver disease (MASLD) remain largely unclear; however, emerging evidence suggests that microRNAs (miRNAs) play a critical role in modulating transcriptional regulation of target genes involved in MASLD. This study aims to elucidate the role of miR-93 in lipid metabolism and MASLD progression.

We comprehensively analyzed miRNA expression profiles in liver tissues from patients with MASLD and diet-induced obese mice. miR-93 knockout (KO) mice were fed a high-fat-high-fructose (HFHFr) diet to assess the impact of miR-93 deficiency on MASLD. Transcriptome analysis was performed to elucidate the molecular mechanisms and role of miR-93 in MASLD. Additionally, we employed a high-throughput screening system to identify drugs capable of modulating miR-93 expression.

miR-93 was significantly upregulated in the livers of patients with MASLD and diet-induced obese mice. miR-93 KO mice exhibited reduced hepatic steatosis. Specifically, miR-93 deficiency upregulated genes involved in fatty acid oxidation and downregulated genes associated with cholesterol biosynthesis. Sirtuin 1 (SIRT1) was identified as a direct target of miR-93, and miR-93 KO enhanced SIRT1 expression and activated the LKB1-AMPK signaling pathway. Niacin treatment downregulated miR-93, ameliorating hepatic steatosis by enhancing SIRT1 activity.

These findings implicate miR-93 as a novel therapeutic target for MASLD. The study demonstrates the therapeutic potential of niacin in modulating the miR-93/SIRT1 axis, providing a new potential treatment for MASLD, a disease with limited current treatment options.

To investigate whether endometriosis is associated with the risk of incident nonalcoholic fatty liver disease (NAFLD).

Data were retrieved from Nurses' Health Study II with participants followed up from 1995 to 2017. A total of 61,649 participants were included in this prospective cohort study. The exposure of this study was laparoscopically confirmed endometriosis. We performed Cox proportional hazard regression analyses to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) of the association between endometriosis and NAFLD.

A total of 4,774 incident NAFLD cases were recorded during a 1,313,067 person-years of follow-up. In the multivariable adjusted model, laparoscopically confirmed endometriosis was positively associated with the risk of NAFLD (HR: 1.17, 95% CI: 1.07 - 1.29). The results of the mediation analyses revealed that the association was partly attributable to hysterectomy/oophorectomy (31.6% mediated, 95% CI: 18.8-47.9%), hypercholesterolemia, hypertension and infertility. Further analysis revealed that the interaction effect of age was significant for the association between endometriosis and NAFLD (P = 0.01).

Laparoscopically confirmed endometriosis was positively associated with the risk of incident NAFLD. Awareness of the potential NAFLD risk should be raised for clinicians and patients during the regular follow-up of endometriosis.

Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated fatty liver disease (MAFLD), is a leading cause of liver disease worldwide and can progress to cirrhosis and cancer. Despite its prevalence, the pathogenesis of MASH remains poorly understood, and there is only one U.S. Food and Drug Administration-approved treatment, highlighting the need for new therapeutic strategies. Peroxisome proliferator-activated receptor (PPAR)γ is activated in the liver under high-fat or obese conditions, promoting lipid storage and contributing to MASH progression. We found that USP28 expression is elevated in the livers of MAFLD/MASH patients. Through dietary induction, including a methionine-choline deficient (MCD) diet and a western diet (WD) combined with carbon tetrachloride (CCl4) injections, we established two severe mouse models of MASH to explore the role of USP28. Mechanistically, the hepatic deubiquitinase (DUB) USP28 directly binds to PPARγ, preventing its ubiquitination and subsequent degradation, thereby maintaining the integrity of the PPARγ signaling pathway. In the absence of Usp28 or if the DUB is inhibited, PPARγ is downregulated, and the PPAR signaling pathway is inhibited, enhancing cellular defenses against excess fat. Both genetic and pharmacological inactivation of Usp28 significantly reduced MASH severity induced by the MCD diet or WD-CCl4 regimen, as well as WD-CCl4-induced hepatocellular carcinoma in mice.

Metabolic dysfunction-associated steatotic liver disease is a significant driver of the increasing global burden of chronic liver disease. This study aimed to describe the temporal trends and inequalities of liver complications related to metabolic dysfunction-associated steatotic liver disease (LC-MASLD) by geographical region, age and sex during 1990-2021.

Global Burden of Diseases Study 2021 data were analysed to assess LC-MASLD incidence, prevalence, mortality and disability-adjusted life years (DALYs). Temporal trends during 1990-2021 were measured by 'estimated annual percentage change' (EAPC). Inequalities of LC-MASLD burden across countries were evaluated by the slope index of inequality (SII) and the relative concentration index (RCI).

During 1990-2021, LC-MASLD rose annually by 0.73% in incidence and prevalence, 0.19% in mortality and 0.16% in DALYs. In 2021, the Middle East and North Africa had the highest incidence and prevalence and Andean and Central Latin America had the highest mortality and DALY rates. While LC-MASLD incidence was earliest in the 15-19 age group, both prevalence and DALY rates peaked at 75-79 years for both sexes. Inequalities in mortality and DALYs by countries' socioeconomic development index increased during 1990-2021, demonstrated by a decline in SII from -0.09 to -0.56 per 100 000 for mortality and from 1.41 to -7.74 per 100 000 for DALYs. RCI demonstrated similar findings.

The LC-MASLD burden is increasing globally, especially in economically disadvantaged countries, with widening disease inequalities during 1990-2021. Effective prevention and subregional interventions are crucial, with a specific focus on resource optimisation for disadvantaged populations.

Non-alcoholic fatty liver disease (NAFLD) involves abnormal fat accumulation in the liver, mainly as triglycerides. It ranges from steatosis to non-alcoholic steatohepatitis (NASH), which can lead to inflammation, cellular damage, liver fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are crucial for regulating gene expression across various conditions. LncRNAs are emerging as potential putative diagnostic markers for NAFLD-associated HCC.

We used two human and two mouse datasets from the Gene Expression Omnibus to analyze the expression profiles of mRNAs and lncRNAs. We created a network linking lncRNAs, miRNAs, and mRNAs to investigate the relationships among these RNA types. Additionally, we identified NAFLD-related lncRNAs from existing literature. We then quantified the expression levels of four specific lncRNAs, including PVT1, DUBR, SNHG17, and SNHG14, in the serum of 92 Egyptian participants using qPCR. Finally, we performed a Receiver Operating Characteristic analysis to evaluate the diagnostic potential of the candidate lncRNAs.

Our data suggests that maternally expressed gene 3 (MEG3), H19, and DPPA2 Upstream Binding RNA (DUBR) were significantly upregulated, and plasmacytoma variant translocation 1 (PVT1) was markedly downregulated. PVT1 showed the highest diagnostic accuracy for both NAFLD and NASH. The combined panels of PVT1 +H19 for NAFLD and PVT1 +H19 +DUBR for NASH demonstrated high diagnostic potential. Uniquely, PVT1 can distinguish between NAFLD and NASH. PVT1 exhibited strong diagnostic potential for NAFLD and NASH, individually and in combination with other lncRNAs.

Our study identifies four lncRNAs as putative biomarkers with high specificity and accuracy, individually or combined, for differentiating between NAFLD and NASH. Healthy volunteers with PVT1 possess the highest diagnostic accuracy and significantly discriminate between NAFLD and NASH.

MRI proton density fat fraction (MRI-PDFF), controlled attenuation parameters (CAP), and attenuation coefficients (AC) are capable of steatosis characterization and may be useful as noninvasive alternatives for diagnosing hepatic steatosis.

This meta-analysis aimed to evaluate the performance of MRI-PDFF, CAP, and AC in grading hepatic steatosis, using histology as the reference standard.

We conducted a comprehensive search of the PubMed, Cochrane Library, Embase, and Web of Science databases until June 2024. The quality of eligible studies was assessed. Pooled sensitivity, specificity, and area under receiver operating characteristic (AUC) curves were calculated using a bivariate random-effects model. Meta-regression analysis, subgroup analysis, and Deeks' test were performed to explore heterogeneity and assess publication bias.

This meta-analysis included 38 studies with 5056 patients with metabolic dysfunction-associated steatotic liver disease. The AUC values for grading steatosis ≥S1, ≥S2, and ≥S3 were 0.99, 0.89, and 0.90 for MRI-PDFF, 0.95, 0.84, and 0.77 for CAP, and 0.97, 0.90, and 0.89 for AC, respectively. CAP demonstrated lower accuracy for detecting steatosis grades ≥S2 and ≥S3 compared to MRI-PDFF (0.89 vs. 0.84, p<0.001; 0.90 vs. 0.77, p<0.001) and AC (0.90 vs. 0.84, p<0.001; 0.89 vs. 0.77, p<0.001). Subgroup analyses revealed that MRI-PDFF and CAP exhibited superior diagnostic performance in diagnosing ≥S2 and ≥S3 steatosis among individuals in Asia, with a body mass index ≤30 kg/m2, and age <51 years.

A direct comparison with CAP showed greater accuracy for MRI-PDFF and AC in diagnosing moderate and severe steatosis, and similar diagnostic performance for MRI-PDFF and AC. For patients with steatosis, AC should be incorporated into routine ultrasound screening.

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.

Nonalcoholic fatty liver disease (NAFLD) cirrhosis is a significant health concern with a major impact on global morbidity and mortality. This study investigates the association of hemoglobin, albumin, lymphocyte, and platelet (HALP) with all-cause mortality, cardiovascular disease mortality, and cancer-related mortality in patients with NAFLD cirrhosis.

This retrospective cohort study used data from the National Health and Nutrition Examination Survey, assessing 11 550 adults. NAFLD cirrhosis was defined by a hepatic steatosis index greater than 36 and a NAFLD fibrosis score greater than 0.676 in participants without viral hepatitis or excessive alcohol use. The HALP score was categorized into low (<32), moderate (32-48.3), and high (>48.3). Logistic and weighted Cox regression analyses were conducted, along with subgroup and restricted cubic spline analyses.

Higher HALP scores were associated with lower all-cause mortality. Subgroup analyses revealed significant interactions with gender and age, showing a decreased risk of all-cause mortality in males and individuals aged 40 and above with higher HALP scores. A U-shaped relationship between HALP scores and all-cause mortality was observed.

The study demonstrates that HALP is associated with a lower risk of all-cause mortality in the NAFLD cirrhosis population, suggesting that HALP may be a useful predictor of mortality risk.

Males suffer more often from profibrotic changes in liver than females. The underlying mechanism for this sex difference in the prevalence and manifestation of Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) is not yet completely known. We studied male and female mice that were induced to develop MASLD by consuming a "fast food" diet (FFD) and assessed metabolic phenotype as well as liver histology and compared them with mice fed with a matched control diet (CD). Our aim was to check for sex-specific differences in MASLD development in a mouse model of diet-induced profibrotic changes in the liver. Our results demonstrate a clear difference in body weight, fat distribution and changes in liver tissue for male and female mice fed with FFD. We found that female mice stored lipids mainly in subcutaneous and visceral adipose tissue while males increased ectopic lipid accumulation in the liver which resulted in hepatomegaly and increased transforming growth factor β 1 (Tgfb1) and collagen I (Col1a1) expression concomitant to fibrosis development. This was absent in female mice. Analysis of estrogen receptor -α (Esr1) and -β (Esr2) expression revealed an upregulation of Esr2 in livers of male FFD-fed mice whereas in female liver tissue a higher expression in Esr1 could be observed. This study supports Esr1 and Esr2 as potential targets to reverse negative effects of diet-induced profibrotic changes in the liver.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) and heart failure are two intersecting growing pandemics. Studies have demonstrated a strong association between MASLD and heart failure. Liver cirrhosis is a well-recognized complication of MASLD. This study aimed to summarize the potential effects of Ramadan fasting on MASLD, liver cirrhosis, and heart failure. The author searched the SCOPUS and PubMed databases using specific terms. The literature review focused on research articles published in English from 2000 to 2024. Twenty-two articles were selected for this narrative review. Ramadan fasting reduced serum cholesterol serum levels, improved symptoms of heart failure and reduced anthropometric measurements. However, it increased ascitic fluid production and plasma bilirubin levels and might increase the risk of hepatic encephalopathy and upper gastrointestinal haemorrhage in liver cirrhosis. Ramadan fasting might improve symptoms of heart failure and might decrease the risk of heart failure in patients with MASLD. Further research studies are needed to confirm the efficacy and evaluate the safety of Ramadan fasting in patients with heart failure and liver cirrhosis.

To clarify how dietary and lifestyle factors work on diabetes-related cardiovascular disease (CVD), we investigated whether the increased risk of CVD in patients with type 2 diabetes mellitus (T2DM) could be offset by an increase in diet and/or lifestyle with antioxidant potential.

A total of 7,658 individuals from UK Biobank (UKB) with T2DM but no diagnosed CVD were included in this study. We screened combinations of 16 nutrients and/or 4 lifestyles to calculate the Oxidative Balance Score (OBS), dietary OBS (DOBS), and lifestyle OBS (LOBS). Cox proportional hazards (CPH) regression models and mediation statistical models were performed.

After adjusting for covariates, CPH regression models showed inverse associations between both OBS and LOBS and CVD. The highest tertile of LOBS was significantly associated with a lower risk of CVD compared to the lowest tertile, with hazard ratios and 95% CIs as follows: Atherosclerotic Cardiovascular Disease (ASCVD) 0.81 (0.68-0.97), Coronary Artery Disease (CAD) 0.79 (0.67-0.93), Atrial Fibrillation (AF) 0.56 (0.45-0.70) and CVD mortality 0.67(0.51-0.88). Correspondingly, the results of associations between the highest tertile of OBS and risks of CVDs above were ASCVD 0.80 (0.64-0.99), CAD 0.83(0.68-1.01), AF 0.73 (0.57-0.92) and CVD mortality 0.68 (0.50-0.92). No associations between DOBS and CVDs were observed [ASCVD 0.83 (0.66-1.05), CAD 0.86 (0.70-1.05), AF 0.77 (0.60-1.00), and CVD mortality 0.79 (0.57-1.10)]. These results were consistent in stratified analyses. Additionally, we identified a mediating role for C-reactive protein (CRP) and white blood cell count (WBC) in the observed relations, with indirect effect and mediation estimates as follows: CRP - 0.003 6.0% (OBS and CAD), -0.008 17.2%, -0.003 11.7%, and - 0.010 14.5% (OBS/DOBS/LOBS and CVD mortality); WBC - 0.006 14.3%, -0.006 12.6%, -0.006 13.4%, -0.005 23.3% (OBS and CVDs), -0.008 11.8%, -0.008 11.9%, -0.008 11.8%, and - 0.005 5.3% (LOBS and CVDs).

Sustained adherence to diets and lifestyles with high antioxidant potential may significantly reduce the risk of CVD in individuals with T2DM.

Metabolic dysfunction-associated steatotic liver disease (MASLD, previously termed NAFLD, nonalcoholic fatty liver disease) is a complex multifactorial disease showing generally higher prevalence and severity in men than in women. With respect to women, men are also more prone to develop metabolic dysfunction-associated steatohepatitis, fibrosis and liver-related complications. Several genetic, hormonal, environmental and lifestyle factors may contribute to sex differences in MASLD development, progression and outcomes. However, after menopause, the sex-specific prevalence of MASLD shows an opposite trend between men and women, pointing to the relevance of oestrogen signalling in the sexual dimorphism of MASLD. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, that encodes a triacylglycerol lipase that plays a crucial role in lipid metabolism, has emerged as a key player in the pathogenesis of MASLD, with the I148M variant being strongly associated with increased liver fat content and disease severity. Recent advances indicate that carrying the PNPLA3 I148M variant can be a risk factor for MASLD especially for women. To elucidate the molecular mechanisms underlying the sex-specific role of PNPLA3 I148M in the development of MASLD, several in vitro, ex vivo and in vivo models have been developed.

Dysregulation of immune homeostasis can precipitate chronic inflammation, thus significantly contributing to the onset and progression of metabolic and cardiovascular diseases. Myeloid-derived suppressor cells (MDSCs) constitute a heterogeneous population of immature myeloid cells that are mobilized in response to biological stressors such as tissue damage and inflammation. Although MDSCs have been extensively characterized in the contexts of cancer and infectious diseases, emerging evidence highlights their pivotal roles in the pathophysiology of metabolic and cardiovascular disorders. We discuss growing evidence for the involvement of MDSCs in the progression of metabolic and cardiovascular diseases, with the aim of deepening our understanding of MDSCs in cardiometabolic physiology and identifying the necessary steps for the development of innovative MDSC-targeted therapeutic strategies.

Patients receiving statin therapy still suffer from adverse cardiovascular events. Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is a newly proposed concept that shares common metabolic risk factors with cardiovascular disease. This study aimed to investigate the association between MAFLD and adverse cardiovascular outcomes in coronary heart disease (CHD) patients with LDL-C<1.8 mmol/L.

CHD patients with LDL-C<1.8 mmol/L were divided into MAFLD and non-MAFLD groups. Propensity score matching (PSM) was used to control for baseline differences between the two groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs). All MAFLD patients were further stratified into two groups with and without advanced liver fibrosis, according to the Fibrosis-4 (FIB-4) index cutoffs, and the associations between advanced liver fibrosis status and cardiovascular outcomes were analyzed. After PSM, 800 MAFLD and 800 non-MAFLD patients with LDL-C<1.8 mmol/L were analyzed. MAFLD patients exhibited a significantly greater cumulative incidence and risk of MACCEs than non-MAFLD patients (9.6 % versus 6.6 %, p < 0.05; HR 1.48, 95 % CI 1.04-2.1, p < 0.05). Among MAFLD patients with LDL-C<1.8 mmol/L, advanced liver fibrosis staged by the FIB-4 index was associated with an elevated risk for MACCEs (HR 2.91, 95 % CI 1.17-7.19, p < 0.05), all-cause mortality, myocardial infarction (MI) and stent thrombosis.

MAFLD was an independent risk factor for adverse cardiovascular outcomes in CHD patients with LDL-C<1.8 mmol/L. Additionally, advanced liver fibrosis predicts increased risks for adverse cardiovascular events among MAFLD patients. These findings suggest that MAFLD and liver fibrosis screening and management contribute to the residual cardiovascular risk of CHD patients.

Metabolic dysfunction associated steatotic liver disease (MASLD) is prevalent in up to 60% of patients with type 2 diabetes mellitus (T2DM). T2DM accelerates the risk of hepatic fibrosis and hepatocellular carcinoma in patients with MASLD. Our goal in this study was to identify patients with suspected MASLD and hepatic fibrosis in a large T2DM clinic by using noninvasive fibrosis scoring systems.

We conducted a retrospective study of patients with T2DM seen by our endocrinologists at the Medical Faculty Associates (MFA) Diabetes Center in Washington, DC, from November 1, 2021, until November 1, 2022. We included all subjects who were over 18 years old with a hemoglobin A1c (HbA1c) of 6.5 or higher. Patients with a history of significant alcohol consumption, decompensated cirrhosis, previous bariatric surgery, or prior chronic liver disease were excluded from the study. We identified patients at risk for hepatic fibrosis by using the Fibrosis-4 (FIB-4) Index, NAFLD Fibrosis Score (NFS) and AST to Platelet Ratio Index (APRI) when lab values were available.

A total of 1,411 patients were evaluated for T2DM by an endocrinology provider during the one-year period. Out of these, 336 patients met one or more of the exclusion criteria, leaving a total of 1075 patients included in the analysis. The majority were African American (n = 582, 54%), 261 were Caucasian (24.3%), and 85 were Hispanic (7.9%). Most patients were females (n = 675, 62.7%). The mean HbA1c was 8.1 ± 2.3. 643 patients (59.8%) were insulin dependent. Based on FIB-4 scores, we found that 35 (3.9%) patients had a score of > 2.67 associated with advanced fibrosis and 257 (29%) patients with scores of 1.3-2.67 had moderate fibrosis. Using the NFS calculator, there were 281 (28%) patients with values of > 0.675 consistent with F3-F4 disease. 715 (71.8%) patients with values of < 0.675 consistent with F0-F2 fibrosis. A total of 6(< 1%) patients met criteria for advanced fibrosis by APRI scoring.

In our urban Diabetes Center, utilizing the NFS calculator may detect many patients with advanced liver disease. Further research is needed to ensure the internal validity of the non-invasive tests in predicting liver fibrosis and to correlate these findings with transient elastography and other imaging evidence of fatty liver disease.

Non-applicable.

This review explores the correlation of non-alcoholic fatty liver disease (NAFLD) with cognitive function and brain changes. A comprehensive search of relevant studies in the PubMed database up to June 2024 was conducted, including various study designs such as cross-sectional, longitudinal, case-control, and cohort studies. Data were extracted from 24 studies, focusing on study design, sample size, NAFLD diagnosis, control of confounders, key findings, and limitations. Neuropsychological tests utilized within each study were grouped into relevant cognitive domains. Statistical analyses and comparisons were also performed on the observed changes in brain parameters across the studies. The meta-analysis on the domain of general cognition was conducted. Results indicated that NAFLD was significantly associated with general cognition, executive function, attention, and memory. NAFLD impacts the total brain volume, the volumes of specific brain regions and certain high-intensity brain regions, the cerebral blood flow and perfusion, the integrity of nerve fiber bundles, and the brain abnormalities or lesions such as cerebral hemorrhage, cerebral microbleeds, and white matter lesions. NAFLD also affects the thickness and surface area of certain cortical regions and the resting-state brain function MRI indicators in specific brain areas. Despite these findings, the included studies varied in design, population characteristics, and outcome measures, which introduced heterogeneity that might influence the generalizability of the results. Overall, NAFLD is associated with a decline in cognitive function and alterations in certain brain parameters. Furthermore, NAFLD may exert its influence on cognition by impacting brain structure.

NAFLD is a rapidly expanding global health issue that is distinguished by the accumulation of hepatic fat that is not associated with alcohol consumption. Parallel to the increase in obesity and type 2 diabetes mellitus (T2DM), its prevalence is also increasing. Amidst a backdrop of limited epidemiological data, Somalia, which is undergoing urbanization and dietary adjustments, is contending with escalating rates of NAFLD. Our study aims to addresses critical voids in local epidemiological data regarding this subject in Somalia.

The objective of this retrospective study was to evaluate the prevalence of NAFLD and concomitant risk factors among T2DM patients at the Mogadishu Somalia Turkish Training and Research Hospital. A total of 832 patients diagnosed with T2DM between May 2023 and March 2024 were used to analyze the data. Various variables, such as age, sex, diabetic medications, hypertension, insulin resistance, hyperlipidemia, and NAFLD grade, were obtained from electronic medical records. Statistical analyses were conducted to investigate the associations and predictors of NAFLD using descriptive analysis, logistic regression, and multiple regression.

The study cohort was predominately female (57%), with a mean age of 53.48 years. The most prevalent grades of NAFLD were grade 1 and grade 2, with NAFLD being identified in 53.8% of patients. NAFLD displayed a robust correlation with insulin resistance (OR: 52.04), with hypertension (OR: 20.091) and hyperlipidemia (OR: 2.528) following shortly thereafter. These factors collectively account for 57% of the variance in NAFLD, as indicated by multiple regression analysis (R2 = 0.57, F (6,823) = 184.302, p < 0.001).

This investigation emphasizes the presence of a high prevalence of NAFLD among T2DM patients in Mogadishu, Somalia, 53.8% which is substantially influenced by hypertension, insulin resistance, and hyperlipidemia. In this region, the necessity of targeted healthcare strategies to mitigate metabolic liver diseases is underscored by the results.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent among people living with severe obesity (body mass index [BMI] ≥ 35 kg/m2). However, it remains unknown how sex and adipose tissue distribution are related to MAFLD onset and progression into metabolic dysfunction-associated steatohepatitis (MASH) or advanced stages of fibrosis. Methodology: We retrospectively studied patients with severe obesity who were eligible for bariatric surgery. Demographic characteristics, biomarkers, and cardiometabolic comorbidities were reported. Anthropometric indices such as BMI, waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), neck circumference (NC), lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), and body roundness index (BRI) were measured or calculated. MAFLD, MASH, and stages of fibrosis (F1-F4) were established from perioperative liver biopsies. Standardized univariate and multivariate logistic regression analyses were used to examine the association between demographic variables, anthropometric indices, cardiometabolic conditions, and the risk of MASH or severe fibrosis (F2-F4). Results: A total of 2091 participants with severe obesity were included in the analyses; BMI 47.9 ± 7.3 kg/m2, age 46.2 ± 11.2 years, and 68.4% females. Overall, MAFLD prevalence was 79.5%, with 44.5% having MASH and 24.4% having severe fibrosis (Stage 2 or higher). No anthropometric indices of adiposity were associated with MASH or fibrosis severity. In this population, female sex was a risk factor for severe fibrosis (OR: 1.27, 95% CI 1.01-1.59, p < 0.05). Conclusions: MAFLD and MASH are highly prevalent in individuals living with severe obesity, but no anthropometric indices or laboratory tests are good predictors of MAFLD or MASH in this population. When MAFLD is diagnosed, our results suggest that females with severe obesity might be at higher risk of advanced stages of fibrosis.

The term metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed based on a redefinition of the nonalcoholic fatty liver disease (NAFLD) criteria. Our study aimed to address the knowledge gap by comparing the diagnostic accuracy of MAFLD and NAFLD criteria in identifying significant fibrosis among patients with hepatic steatosis. A cross-sectional study was conducted on 2626 patients with hepatic steatosis treated at Beijing Ditan Hospital between January 2009 and December 2022. Patients with viral hepatitis were excluded. Significant fibrosis was defined as a Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) score F ≥ 2. MAFLD and NAFLD were diagnosed in 478 and 428 patients, respectively. Clinicopathological characteristics were compared between the MAFLD+ NAFLD- group (patients who met the criteria for MAFLD but not NAFLD) and MAFLD- NAFLD+ group (patients who met the criteria for NAFLD but not MAFLD). A total of 743 patients with histologically verified hepatic steatosis were analyzed. The MAFLD+ NAFLD- group comprised 163 (21.9%) and the MAFLD- NAFLD+ group comprised 113 (15.2%) patients. Patients in the MAFLD+ NAFLD- group were older and more likely to be male and had higher body mass index and liver stiffness levels than those in the MAFLD- NAFLD+ group. The prevalence of significant fibrosis was higher in the MAFLD+ NAFLD- group than in the MAFLD- NAFLD+ group (43.6% vs 15.9%, P < .001). The MAFLD criteria may be a better indicator of fibrosis than the NAFLD criteria. Fibrosis in patients with MAFLD can be determined by metabolic disorders, not excessive alcohol consumption.

Hepatic de novo lipogenesis (DNL) is increased by both carbohydrate intake and protein consumption. In hepatic fat synthesis, a key role is played by the induction of the hepatic expression of lipogenic genes, including Fasn, Scd1, and Srebf1. Regarding carbohydrate intake, increased blood glucose and insulin levels promote the expression of hepatic lipogenic genes. However, although amino acids serve as a carbon source for hepatic DNL during protein consumption, their effects on hepatic lipogenic gene expression remain unclear. We investigated the effects of amino acids on hepatic lipogenic gene induction using primary cultured mouse hepatocytes and hepatic Fasn reporter (l-FasnGLuc) mice. In primary cultured hepatocytes, lipogenic gene expression (Fasn, Scd1, Srebf1) was induced under postprandial-mimicking conditions (treatment with insulin and LXR agonist). When hepatocytes were stimulated with an amino acid mixture containing 20 amino acids, the induction of lipogenic gene expression was enhanced, but this effect disappeared when proline was removed from the mixture. Furthermore, when each amino acid was tested individually, only proline potentiated the induction of lipogenic gene expression in hepatocytes under postprandial-mimicking conditions. In mouse liver, continuous proline infusion via osmotic pump increased Fasn gene expression and showed a trend toward increased Srebf1 expression. In l-FasnGLuc mice, continuous proline infusion resulted in sustained enhancement of hepatic Fasn transcription, measured by secreted luciferase activity. These results demonstrate that proline enhances the induction of hepatic lipogenic gene expression both in vitro and in vivo.

Hepatic steatosis (HS) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥ 7.5% are associated with increased risk for cardiovascular events.

To assess underlying coronary artery disease (CAD) and major adverse cardiovascular event (MACE) among those with and without HS at different ASCVD risk.

We evaluated stable chest pain patients receiving coronary computed tomography (CT) in the PROMISE trial. HS and CAD endpoints were defined on coronary CT. MACE was defined as unstable angina, non-fatal myocardial infarction, and all-cause death. Multivariable Cox regression, adjusting for CAD characteristics, assessed the association of HS with MACE for ASCVD < 7.5%.

One thousand two hundred and four of 3702 (32.5%) patients were at ASCVD < 7.5% and 20.3% (244/1204) of them had HS. Individuals with HS were younger (54.3 ± 5.2 vs. 55.8 ± 5.2; p < 0.001), more often males (40.2% [98/244] vs. 27.1% [260/960]; p < 0.001), had more risk factors/person (2.06 ± 0.89 vs. 1.93 ± 0.91; p = 0.047). CAD characteristics were similar between HS vs. non-HS patients at ASCVD < 7.5% and ASCVD ≥ 7.5% (all p > 0.05). Patients with HS had greater MACE rate compared to non-HS patients (ASCVD < 7.5%: 3.75%[9/244] vs. 1.5% [14/960]; p = 0.027 and ASCVD ≥ 7.5%: 4.7% [33/696] vs. 3.1% [56/1802]; p = 0.043). In patients without HS, MACE rate was higher in the ASCVD ≥ 7.5% vs. < 7.5% (3.1% [56/1802] vs. 1.5% [14/960]; p = 0.011). In patients with HS, MACE rates were not significantly different between ASCVD ≥ 7.5% vs. < 7.5% (4.7% [33/696] vs. 3.7% [9/244]; p = 0.484). In ASCVD < 7.5%, HS predicted MACE (aHR:2.34, 95%CI:1.01-5.43; p = 0.048), independent of CAD characteristics.

Individuals with HS at ASCVD < 7.5% risk had similar CAD characteristics as patients without HS at < 7.5% ASCVD risk, yet experienced comparable MACE rates as those at ASCVD ≥ 7.5%.

This study aims to investigate the differences in pathogenic bacterial spectra between patients with deep neck infection (DNI) with and without liver cirrhosis (LC). The goal is to identify specific pathogens prevalent in LC-DNI to guide the selection of empiric antibiotics, improving treatment outcomes and prognosis.

This is a retrospective study.

The Chang Gung Research Database (CGRD) is a deidentified medical database encompassing seven hospitals within Taiwan's largest medical system. We analyzed data from 2004 to 2018 on DNI patients hospitalized with or without LC, categorizing them into these two groups. This study primarily focused on comparing the bacterial culture results of these groups, alongside an analysis of their treatment modalities (medication alone or surgery) and prognostic outcomes.

From a total of 11,455 DNI patients identified in the CGRD, 76 LC-DNI patients and 11,178 non-LC-DNI patients met the inclusion criteria after exclusions. The LC group had significantly higher rates of surgical debridement (34.2% vs. 19.4%, p = 0.002), ICU admission (22.4% vs. 10.7%, p = 0.004), and mediastinal complications (7.9% vs. 2.1%, p = 0.005). Although the overall mortality rates were not significantly different between the two groups (6.6% vs. 4.6%, p = 0.401), the mediastinitis-related mortality rate was significantly higher in the LC-DNI group (2.6% vs. 0.2%, p = 0.015). Bacterial culture analysis revealed that LC-DNI patients predominantly presented with Klebsiella pneumoniae (KP) as the primary facultative anaerobic pathogen, whereas non-LC-DNI patients were most infected with Viridans streptococcus (VS). For anaerobic bacteria, both groups consistently cultured Peptostreptococcus micros and Prevotella intermedia as the predominant species.

LC-DNI patients are predominantly infected with KP, a Gram-negative bacillus, unlike the Gram-positive cocci, VS, in non-LC-DNI. Anaerobic pathogens were similar in both groups. Empiric antibiotics for LC-DNI should target KP and anaerobes to improve outcomes.

3 Laryngoscope, 2025.

Non-alcoholic fatty liver disease (NAFLD) is a disease with various levels varying from fatty liver steatosis to acute steatosis which is non-alcoholic steatohepatitis (NASH), which can develop into hepatic failure, as well as in some conditions it can develop into hepatocellular carcinoma (HCC). In the NAFLD and NASH context, aberrant microRNA (miRNA) expression has a thorough contribution to the incidence and development of these liver disorders by influencing key biological actions, involving lipid metabolism, inflammation, and fibrosis. Dysregulated miRNAs can disrupt the balance between lipid accumulation and clearance, exacerbate inflammatory responses, and promote fibrogenesis, thus advancing the severeness of the disorder from simple steatosis to more complex NASH. In the current review, the latest development concerned with the activity of complex regulatory networks of miRNA in the incidence as well as the evolution of NAFLD is to be discussed, also conferring about the miRNAs' role in the onset, pathogenesis as well as diagnosis of NAFLD and NASH discussing miRNAs' role as diagnostic biomarkers and their therapeutic effects on NAFLD/NASH.

Metabolic associated steatohepatitis characterized by lipid accumulation, inflammation and fibrosis, is a growing global health issue, contributing to severe liver-related mortality. With limited effective treatments available, there is an urgent need for novel therapeutic strategies. Moringa oleifera, rich in antioxidants, offers potential for combating steatohepatitis, but its cytotoxicity presents challenges. Aloe vera, renowned for its cytocompatibility and anti-inflammatory effects, shows promise in mitigating these risks. Using infrared spectrometry and mass spectrometry, we identified 1586 metabolites from both plants across 84 chemical classes. By encapsulating these phytochemicals in nanoparticles, we achieved increased solubility, cytocompatibility, and gene modulation to hepatic stellate cells affected by steatohepatitis. Chemoinformatic analysis revealed bioactive metabolites, including hesperetin analogs, known to inhibit TGF-β. Our results demonstrate that these nanoparticles not only improved gene expression modulation related to metabolic associated steatohepatitis, particularly TGF-β and COL1A1, but also outperformed free compounds, highlighting their potential as a novel therapeutic approach.

The global burden of non-alcoholic steatohepatitis (NASH)-related liver cancer (NRLC) is increasing, making NASH the fastest-growing cause of liver cancer worldwide. This study presents a comprehensive analysis of NRLC burden at the global, regional, and national levels, further categorized by age, sex, and sociodemographic index (SDI).

Data on NRLC from the Global Burden of Disease, Injuries, and Risk Factors (GBD) study 2021 were downloaded at global, regional, and national levels. The numbers and age-standardized rates (ASRs) of incidence, mortality, and disability-adjusted life years (DALYs) were analyzed to quantify the global burden of NRLC. Additionally, percentage changes in ASRs were used to identify trends in NRLC from 1990 to 2021.

Globally, both the number of cases and ASRs for NRLC increased between 1990 and 2021. In 2021, there were 42,291 new cases, 40,925 deaths, and 995,475 DALYs attributed to NRLC. East Asia, South Asia, and Southeast Asia reported the highest absolute case numbers, while Western, Southern, and Eastern Sub-Saharan Africa exhibited the highest ASRs. From 1990 to 2021, Australasia, Southern Latin America, and High-income North America showed the most significant increases in NRLC incidence. Nationally, Mongolia, Gambia, and Mozambique exhibited the highest ASR in 2021.The greatest percentage increases in ASIR occurred in Australia, the United Kingdom, and New Zealand between 1990 and 2021. NRLC incidence rates were higher in men and increased with age, peaking at 80-89 years. Similar patterns were observed for NRLC-related deaths and DALYs. Regionally, ASRs initially declined but then increased as SDI rose. At the national level, ASRs consistently decreased with higher SDI.

This study highlights the substantial burden of NRLC at global, regional, and national levels. Males and older individuals bear a higher disease burden, and considerable variation exists across different regions and countries. These findings provide critical insights for formulating effective strategies to prevent and manage NRLC.

Metabolic dysfunction-associated fatty liver disease (MAFLD) presently poses a threat to approximately 24% of the global population. The consumption of healthy diets rich in an abundant assortment of vegetables has been scientifically validated to mitigate the progression of MAFLD. However, it remains uncertain whether all categories of vegetables confer benefits for MAFLD. The objective of this study is to investigate the impact of different types of vegetables on MAFLD, aiming to provide a scientific basis for developing more appropriate dietary recommendations for individuals at high risk of MAFLD.

We investigated the associations between various types of vegetable consumption and the risk of MAFLD, utilizing data sourced from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cycle. Employing multiple logistic regression and subgroup analyses, we estimated odds ratios (ORs) and 95% confidence intervals (CIs).

Our analysis encompassed a total of 3162 participants. Remarkably, heightened intake of dark green vegetables demonstrated an innovative association with reduced odds of MAFLD (OR = 0.54; 95% CI: 0.36-0.81; p-value = 0.01), while other kinds of vegetable shown no significant association with MAFLD in the full adjusted model (all p-vale > 0.05). In the subgroup analysis, a prominent inverse correlation between the consumption of dark green vegetables and MAFLD was discerned among female and non-Hispanic white people with higher educational attainment.

Our study conclusively demonstrates that a heightened intake of dark green vegetables is linked to diminished odds of MAFLD.

Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), which have a reciprocal relationship compounded by obesity, are highly prevalent in the Middle East affecting morbidity, mortality, and healthcare costs.

This study aimed to assess the severity of MASLD and liver fibrosis among adult Emirati patients with long-standing T2DM.

This cross-sectional study used noninvasive methods to assess the severity of MASLD and fibrosis progression in an adult cohort of Emirati patients (N = 546) with a mean T2DM duration of 16 years.

Fatty liver infiltration was assessed by hepatic steatosis index (HSI), while fibrosis was assessed by the fibrosis-4 (FIB-4) index and aspartate aminotransferase/platelet ratio index (APRI). Of those, 108 patients were randomly subjected to ultrasound-based FibroScan® to assess controlled attenuation parameter (CAP) and liver stiffness measurement (LSM).

All patients had fatty liver with ~ 83% being categorized as having severe steatosis. Serum-based fibrosis biomarker panels detected significant liver fibrosis in ~ 2.5% of these patients. The APRI appeared to be more restrictive in detecting moderate fibrosis (1.5%) than the FIB-4 index (25.5%). CAP significantly correlated with the LSM, indicating that the two methods contributed to the same underlying pathophysiology. Liver steatosis was more severe in female patients, who were older and had a higher body mass index (BMI) than those with moderate or no significant fibrosis. They also had higher serum liver enzymes and were more likely to have age-related changes in kidney function. Interestingly, severity of both steatosis and fibrosis remained unaffected by age and duration of T2D except for fibrosis severity detected by FibroScan®.

This study highlights the critical need for routine screening of MASLD among Emirati patients with long-standing T2DM, given the high point prevalence of severe steatosis (~ 83%), predominantly among women in this population.

Macrophages play important roles in metabolic dysfunction-associated steatohepatitis (MASH), an advanced and inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD). In humans and mice, the cellular heterogeneity and diverse function of hepatic macrophages in MASH have been investigated by single cell RNA sequencing (scRNA-seq). However, little is known about their roles in rats. Here, we collected liver tissues at the postnatal week 16, when our previously characterized Lep∆I14/∆I14 rats developed MASH phenotypes. By scRNA-seq, we found an increase in the number of macrophages and endothelial cells and a decrease in that of NK and B cells. Hepatic macrophages in rats underwent a unique M1 to M2 transition without expression of the classical markers such as Arg1 and Nos2, except for Cd163. Lipid-associated macrophages (LAMs) were increased, which could be detected by the antibody against Cd63. In the microenvironment, macrophages had an increased number of interactions with hepatocytes, myofibroblasts, T cells, neutrophils, and dendritic cells, while their interaction strengths remained unchanged. Finally, the macrophage migration inhibitory factor (MIF) pathway was identified as the top upregulated cell-communication pathway in MASH. In conclusion, we dissected hepatic macrophage dynamics during MASH at single cell resolution and provided fundamental tools for the investigation of MASH in rat models.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and it is not only the keystone precursor of eventual liver-related morbidity, but it also places patients at considerably higher cardiovascular risk, which is still a leading cause of death in these patients. The most important common underlying pathophysiological mechanisms in these diseases are primarily related to insulin resistance, chronic inflammation and oxidative stress. The presence of MASLD with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) elevates the risk for poor outcomes, thus this review highlights a method to the therapeutic approaches. Given the intertwined nature of MASLD, T2DM, and CVD, there is an urgent need for therapeutic strategies that address all three conditions. Although lifestyle changes are important as treatment, medication plays a crucial role in managing hyperglycemia, enhancing liver function and lowering cardiovascular risk. The onset and progression of MASLD should be addressed through a multifaceted therapeutic approach, targeting inflammatory, immune, metabolic, oxidative stress, hormonal and gutaxis pathways, alongside the treatment strategies for T2DM. In this review, we discuss the effects of antidiabetic drugs with an impact on both liver outcomes and cardiovascular risk in patients affected by MASLD, T2DM and CDV.

Intermittent fasting (IF) can be an effective dietary therapy for weight loss and improving cardiometabolic health. However, there is scant evidence regarding the role of IF on indicators of liver function, particularly in adults with metabolic disorders. Therefore, we performed a systematic review and meta-analysis to investigate the effects of IF on liver function in adults with metabolic disorders.

Three primary electronic databases including PubMed, Web of Science, and Scopus, were searched from inception to September 2024 to identify original studies that used IF interventions with or without control groups in adults with metabolic disorders. Inclusion criteria were (1) studies of human participants with metabolic diseases, (2) interventions that evaluated the effects of IF, (3) with or without a control group, and (4) measured liver fat, liver steatosis, liver fibrosis, or liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as primary outcomes. Standardized mean differences (SMD) and 95% confidence intervals were calculated using random effects models. Heterogeneity was assessed using the Cochran's Q statistic and I-squared statistic (I2). Publication bias was assessed using the visual inspection of funnel plots and Egger's tests. The risk of bias was assessed using the PEDro scale and the NIH quality assessment tool.

A total 21 studies involving 1,226 participants with metabolic disorders were included in the meta-analysis. Overall, IF effectively decreased liver fat with a large effect size [SMD: -1.22 (95% CI: -1.63 to -0.80), p = 0.001], liver steatosis with a medium effect size [SMD: -0.73 (95% CI: -1.12 to -0.35), p = 0.001], ALT with a small effect size [SMD: -0.44 (95% CI: -0.58 to -0.30), p = 0.001], and AST with a small effect size [SMD: -0.30 (95% CI: -0.49 to -0.11), p = 0.001], but not liver fibrosis [SMD: -0.28 (95% CI: -0.59 to 0.02), p = 0.07]. Subgroup analyses showed that IF decreased liver fat and ALT significantly, independent of IF mode, participant age, health status, weight status, and intervention duration. IF significantly decreased liver fibrosis in those with obesity; and decreased AST following 5:2 diets, in middle-aged adults, adults with obesity, and regardless of health status or intervention duration.

IF seems to be an effective dietary therapy for improving liver function in adults with metabolic disorders, and many of liver function-related benefits occur regardless of IF mode, intervention duration, or participant health status.

Significant heterogeneity, small numbers of studies and inclusion of non-randomized trials or single-group pre-post trials were the main limitation of our meta-analysis. Further randomized clinical trials are needed to elucidate the effects of IF on liver function in adults with metabolic disorders.