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Alterations in tricarboxylic acid (TCA) cycle metabolism are associated with hepatic metabolic disorders. Elevated hepatic acetate concentrations, often attributed to high caloric intake, are recognized as a pivotal factor in the etiology of obesity and metabolic syndrome. Therefore, the assessment of acetate breakdown and TCA cycle activity plays a central role in understanding the impact of diet‐induced alterations on liver metabolism. Magnetic resonance‐based deuterium metabolic imaging (DMI) could help to unravel the underlying mechanisms involved in disease development and progression, however, the application of conventional deuterated glucose does not lead to substantial enrichment in hepatic glutamine and glutamate. This study aimed to demonstrate the feasibility of DMI for tracking deuterated acetate breakdown via the TCA cycle in lean and diet‐induced fatty liver (FL) rats using 3D DMI after an intraperitoneal infusion of sodium acetate‐d3 at 9.4T. Localized and nonlocalized liver spectra acquired at 10 time points post‐injection over a 130‐min study revealed similar intrahepatic acetate uptake in both animal groups (AUCFL = 717.9 ± 131.1 mM▯min−1, AUClean = 605.1 ± 119.9 mM▯min−1, p = 0.62). Metabolic breakdown could be observed in both groups with an emerging glutamine/glutamate (Glx) peak as a downstream metabolic product (AUCFL = 113.6 ± 23.8 mM▯min−1, AUClean = 136.7 ± 41.7 mM▯min−1, p = 0.68). This study showed the viability of DMI for tracking substrate flux through the TCA cycle, underscoring its methodological potential for imaging metabolic processes in the body. [ABSTRACT FROM AUTHOR]

Aims Materials and Methods Results Conclusions This study aimed to evaluate the effectiveness of imeglimin in improving liver function and fibrosis in patients with type 2 diabetes (T2D) complicated by metabolic dysfunction‐associated steatotic liver disease (MASLD).We conducted a multicentre study involving 80 patients with T2D and MASLD who were treated with or without imeglimin for 24 weeks. We assessed the changes in diabetes‐related parameters, including HbA1c, fasting blood glucose, glycoalbumin and C‐peptide index. Liver function was monitored using AST, ALT, γ‐GTP and liver fibrosis indicators such as Fib‐4 index and FibroScan‐AST (FAST) score. Liver fat content and stiffness were measured using controlled attenuation parameter and vibration‐controlled transient elastography, which were measured using FibroScan.Compared with the control group, imeglimin treatment led to a significant reduction in HbA1c levels, fasting blood glucose and liver‐related parameters, including AST, ALT and γ‐GTP. Additionally, the Fib‐4 index and FAST score, which reflect liver fibrosis and inflammation, were significantly lower in the imeglimin group. Liver fat content and stiffness remained unchanged during the study period.Imeglimin efficaciously improved liver inflammation and fibrosis in patients with T2D and MASLD, with no significant changes in liver fat content or stiffness. These findings suggest that imeglimin is a promising therapeutic drug for the management of MASLD in the context of T2D, warranting further research on its long‐term efficacy and mechanisms of action. [ABSTRACT FROM AUTHOR]

The gut microbiota plays a pivotal role in influencing the metabolism and immune responses of the body. A balanced microbial composition promotes metabolic health through various mechanisms, including the production of beneficial metabolites, which help regulate inflammation and support immune functions. In contrast, imbalance in the gut microbiota, known as dysbiosis, can disrupt metabolic processes and increase the risk of developing diseases, such as obesity, type 2 diabetes, and inflammatory disorders. The composition of the gut microbiota is dynamic and can be influenced by environmental factors such as diet, medication, and the consumption of live bacteria. Since the early 1900s, bacteria isolated from food and have been used as probiotics. However, the human gut also offers an enormous reservoir of bacterial strains, and recent advances in microbiota research have led to the discovery of strains with probiotic potentials. These strains, derived from a broad spectrum of microbial taxa, differ in their ecological properties and how they interact with their hosts. For most probiotics bacterial structural components and metabolites, such as short‐chain fatty acids, contribute to the maintenance of metabolic and immunological homeostasis by regulating inflammation and reinforcing gut barrier integrity. Metabolites produced by probiotic strains can also be used for bacterial cross‐feeding to promote a balanced microbiota. Despite the challenges related to safety, stability, and strain‐specific properties, several newly identified strains offer great potential for personalized probiotic interventions, allowing for targeted health strategies. [ABSTRACT FROM AUTHOR]

The meta-analysis study examines the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in children and adolescents with type 1 diabetes. The study included nine cross-sectional studies with 1007 participants, showing an overall MASLD prevalence of 16.69%. Variations in prevalence were observed based on world region and diagnostic method. The study highlights the importance of early detection and management of MASLD in this population, emphasizing the need for further research to validate these findings and explore screening recommendations. [Extracted from the article]

Background Methods Results Conclusions Type 2 diabetes increases the risk of cirrhosis and liver cancer. Noninvasive and early assessment of liver fibrosis is essential. We aimed to develop a score to aid in the initial assessment of liver fibrosis in the diabetic population.A fibrosis investigating navigator in diabetes (FIND) score was developed and validated in the NHANES dataset (2017–2020). Fibrosis was defined as a liver stiffness measurement (LSM) ≥8.0 kPa. The diagnostic accuracies of FIB‐4, NFS, LiverRisk, steatosis‐associated fibrosis estimator (SAFE) and metabolic dysfunction–associated fibrosis (MAF‐5) were compared. FIND was also externally validated in various liver diseases via biopsy as a reference in an Asian centre between 2016 and 2020. Finally, we examined the prognostic implications of the FIND index utilizing data from the UK Biobank cohort (2006–2010).The FIND score model yielded an AUROC of 0.781 for the prediction of an LSM ≥8 kPa in the validation set, which was consistently greater than that of other available models (all p < 0.05). In the whole NHANES dataset, the 85% sensitivity cut‐off of 0.16 corresponded to a NPV of 91.9%, whereas the 85% specificity cut‐off of 0.31 corresponded to a PPV of 50.6%. FIND displayed overall accuracies similar to those of the other models in staging fibrosis stages, with biopsy used as a reference. In the UK Biobank cohort, FIND >0.31 was associated with an increased risk of all‐cause and liver‐related mortality in the diabetic population in adjusted models (HR, 1.75; 95% CI, 1.62–1.89; HR, 23.59; 95% CI, 13.67–40.69).In diabetes patients, the novel FIND score performs well in identifying subjects at risk of liver fibrosis and predicting all‐cause and liver‐related mortality. [ABSTRACT FROM AUTHOR]

This review focuses on a special aspect of hepatic lipid storage and inflammation that occurs during nutritional excess in obesity. Mounting evidence supports that prolonged excess fatty acid (FA) uptake in the liver is strongly associated with hepatic lipid storage and inflammation and that the two processes are closely linked by a homeostatic mechanism. There is also strong evidence that bacterial lipids may enter the gut by a common mechanism with lipid absorption and that there is a set point to determine when their uptake triggers an inflammatory response in the liver. In fact, the progression from high uptake of FAs in the liver resulting in Metabolic dysfunction‐associated steatotic liver disease (MASLD) to the development of the more serious Metabolic dysfunction‐associated steatohepatitis (MASH) depends on the degree of inflammation and its progression from an acute to a chronic state. Thus, MASLD/MASH implicates both excess fatty acids and progressive inflammation in the aetiology of liver disease. We start the discussion by introduction of CD36, a major player in FA and lipopolysaccharide (LPS) uptake in the duodenum, liver and adipose tissue. We will then introduce CEACAM1, a major player in the regulation of hepatic de novo lipogenesis and the inflammatory response in the liver, and its dual association with CD36 in enterocytes and hepatocytes. We conclude that CEACAM1 and CD36 together regulate lipid droplet formation and inflammation in the liver. [ABSTRACT FROM AUTHOR]

Background: Fatty liver disease (FLD) is the common metabolic disease of liver with high worldwide prevalence. Nonalcoholic FLD may progress to acute hepatitis, chronic liver disease and even into hepatocellular carcinoma. Noninvasive parameters based on diagnostic imaging should be sought as the only diagnostic test available for this condition is liver biopsy. Objectives: The objectives of this study are to correlate abdominal adiposity indicators, specifically visceral adipose tissue (VAT) thickness and subcutaneous adipose tissue (SAT) thickness, with body mass index (BMI) and fatty liver disease (FLD) grades using ultrasound, and to evaluate the diagnostic ability of the parameter "VAT thickness of 3 cm or above" in detecting hepatic steatosis. Method: Total 100 patients were examined by ultrasound to evaluate VAT, SAT and FLD grades. All patients showing findings of steatotic liver were considered as cases and those showing normal liver findings were considered as controls. Correlation coefficient for VAT, SAT, BMI and FLD grades were calculated and p-value was derived. Sensitivity, Specificity, ROC curve and AUC value for parameter "VAT thickness 3 cm or above" was calculated. Results: A total of 100 patients were examined including 33 males and 67 females. The mean age of patients was 42.34 ± 12.87 years. Mean VAT thicknesses was 3.69 ± 1.61 cm. The mean SAT thickness was 2.00 ± 0.86 cm. Mean BMI was 25.28 ± 5.13 kg/m2 (Overweight). Positive correlation of VAT and SAT measurements seen with BMI and FLD grades." VAT thickness 3 cm or above", to detect FLD has a good diagnostic ability with Sensitivity (95%), Specificity (96%), PPV (95%), NPV (96%) and area of curve value 0.8 to detect FLD. Conclusion: The abdominal fat indicators were positively correlated with BMI and FLD grades. The parameter "VAT thickness 3 cm or above" has a good diagnostic efficacy to detect FLD and may be utilized as an alternative to liver biopsy. [ABSTRACT FROM AUTHOR]

Objective: We aimed to elucidate the effectiveness of Sodium-glucose co-transporter-2 inhibitors (SGLT2-I) in the reduction of ALT among Type-2 diabetes patients (T2DM) with Non-alcoholic fatty liver disease (NAFLD). Methods: We retrospectively collected data from 120 files of T2DM, aged 30-60 years, with elevated ALT, and documented follow-up for one year from August 2018 - July 2019. The effects of SGLT2Is (Dapagliflozin and Empagliflozin) were evaluated using Generalized Estimating Equation (GEE) for analysis. Results: The overall mean age was 48.9 ± 7.3 years, 57.5% were females, and the mean duration of diabetes was 8.5 ± 5.6 years. At baseline, the mean BMI was 32.5 ± 5.7 kg/m2, mean ALT was 51.6 IU/L ± 17.8 IU/L, and mean HbA1c was 8.5% ± 1.5%. There was a statistically significant reduction in mean ALT of 2.2 IU/L (p-value 0.02) with every 10 mg/dl increase in LDL among females using 10 mg Empagliflozin as compared to males not on SGLT2i. Conclusions: We observed an average reduction in mean ALT levels when SGLT2Is was initiated in T2DM patients having NAFLD. Apart from encouraging diet and lifestyle modification, early intervention with SGLT2Is may decrease liverrelated morbidity and mortality resulting from NAFLD. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease, affecting approximately one-fourth of adults worldwide, and is the leading cause of liver-related morbidity and mortality. MASLD is a sex-dimorphic disease, with a general higher prevalence in men. Women in fertile age exhibit a lower risk of MASLD than men. However, after menopause, their prevalence of MASLD becomes comparable to that of men. A complex interaction of gender-specific factors contributes to MASLD varying prevalence and severity. Sex is rarely considered as a biological variable in preclinical and clinical studies of MASLD. Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common chronic liver condition. MASLD is a sexually dimorphic condition, with its development and progression influenced by sex chromosomes and hormones. Estrogens typically protect against, whereas androgens promote, MASLD. Therapeutic approaches for a sex-specific personalized medicine include estrogen replacement, androgen blockers, and novel drugs targeting hormonal pathways. However, the interactions between hormonal factors and inherited genetic variation impacts MASLD risk, necessitating more tailored therapies. Understanding sex disparities and the role of estrogens could improve MASLD interventions and management, whereas clinical trials addressing sex differences are crucial for advancing personalized treatment. This review explores the underappreciated impact of sexual dimorphism in MASLD and discusses the potential therapeutic application of sex-related hormones. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non‐alcoholic fatty liver disease, focusing particularly on ferroptosis‐related pathways and its reliance on nuclear factor erythroid 2‐related factor 2. Materials and Methods: Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis‐related gene expression in vivo. Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels. Results: Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low‐density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin‐1β and tumour necrosis factor‐α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high‐fat diet‐induced non‐alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2‐related factor 2 and its downstream ferroptosis‐related genes to inhibit ferroptosis in the livers of rats with non‐alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis‐related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear factor erythroid 2‐related factor 2. Conclusions: This study highlights the potential of diosgenin from Dioscoreaceae plants in mitigating oxidative stress and ferroptosis levels through nuclear factor erythroid 2‐related factor 2 regulation, offering novel insights into the treatment of non‐alcoholic fatty liver disease and other metabolic disorders through traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

The available literature on the effect of apolipoprotein C-III (ApoC-III) inhibition in MASLD reveals inconsistencies. The aim of the present work was to examine levels of ApoC-III in the entire spectrum of metabolic-dysfunction associated steatotic liver disease (MASLD). This is a multicenter study involving patients enrolled in two gastroenterology-hepatology clinics (Greece and Australia) and in a bariatric-metabolic surgery clinic (Italy), with liver biopsy before and after bariatric surgery or lifestyle modification. Comparing simple MASL to steatohepatitis (MASH) with fibrosis stage F ≥ 2 (at-risk MASH), revealed a marginally significant trend for decreased ApoC-III levels in the latter group (p = 0.07). Multi-adjusted analysis revealed an inverse association between ApoC-III and at-risk MASH (Odds Ratio per 1 mg/dL increase in ApoC-III = 0.91, 95 % Confidence Interval (0.83, 0.99)). ApoC-III interacted with triglycerides in predicting at-risk MASH (p-for-interaction = 0.002). Participants with ApoC-III > median (∼3.75 mg/dL) and normal triglycerides (triglyceridese≤150 mg/dL) had the lowest likelihood to present at-risk MASH (31.8 %) in contrast with participants with ApoC-III < median and hypertriglyceridemia among whom at-risk MASH was recorded in 57.1 %. In multi-adjusted analysis participants with normal triglycerides and high ApoC-III had 64 % lower odds of at-risk MASH compared with their counterparts with ApoC-III < median (OR = 0.36, 95%CI (0.14, 0.86)). Among participants with hypertriglyceridemia, those with ApoC-III < median had less prevalent at-risk MASH compared with those with ApoC-III ≥ median (OR = 0.54, 95%CI (0.32, 0.98)); however in all cases significance was lost when liver enzymes were taken into account. In advanced disease stages, ApoC-III levels seem to be decreased and advanced organ damage may be a potential explanation. Mendelian randomization studies are needed to confirm or refute this hypothesis. [ABSTRACT FROM AUTHOR]

In recent lab‐based experiments, some post‐smolt Atlantic salmon (Salmo salar) held at 3°C for 5 weeks exhibited a range of clinical signs. They became lethargic and swam at the water's surface, developed ulcers to the head and jaw (clinical signs similar to tenacibaculosis in Norwegian salmon aquaculture) and had fin erosion, and this was associated with significant mortalities. In addition, when fish with 'early' and 'advanced' stages of these different clinical signs were further examined, their livers were found to be large, pale and friable. Fish with this aetiology also had elevated aspartate aminotransferase levels (indicative of liver damage), elevated plasma [Na+], [Cl−] and osmolality (indicating osmoregulatory impairment), low glucose levels (likely limiting metabolic responses to maintain homeostasis) and high circulating cortisol levels (∼100 ng/mL). This suite of physiological disturbances is very similar to that observed in a condition referred to as 'Winter Syndrome' or 'Winter Disease' (WS/WD) in cultured gilthead sea bream (Sparus aurata) and other fish species. Thus, it appears that WS/WD described here for the first time in Atlantic salmon, alone or in combination with opportunistic infections, results in lipid deposition in the liver, compromising liver function and osmoregulatory capacity, and metabolic collapse that ultimately results in significant losses. [ABSTRACT FROM AUTHOR]

The human gut microbiome plays a crucial role in regulating intestinal and systemic health, impacting host immune response and metabolic function. Dysbiosis of the gut microbiome is linked to various diseases, including steatotic liver diseases. Metabolic dysfunction‐associated steatotic liver disease (MASLD), a chronic liver disease characterized by excess hepatic lipid content and impaired metabolism, is the leading cause of liver disease worldwide. Among the gut microbes, Ruminococcus gnavus (R. gnavus) has garnered attention for its association with inflammatory and metabolic diseases. While R. gnavus abundance correlates to liver fat accumulation, further research is needed to identify a causal role or therapeutic intervention in steatotic liver disease. This review surveys our current understanding of R. gnavus in the development and progression of steatotic liver diseases, highlighting its potential mechanisms through metabolite secretion, and emphasizes the need for comprehensive microbiome analyses and longitudinal studies to better understand R. gnavus' impact on liver health. This knowledge could pave the way for targeted interventions aimed at modulating gut microbiota to treat and prevent MASLD and its comorbidities. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD). METHODS: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC. RESULTS: After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95%CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference. DISCUSSION: This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention. [ABSTRACT FROM AUTHOR]

The nervous system significantly participates in maintaining homeostasis, and modulating repair and regeneration processes in the liver. Moreover, the nervous system also plays an important role in the processes associated with the development and progression of liver disease, and can either potentiate or inhibit these processes. The aim of this review is to describe the mechanisms and pathways through which the nervous system influences the development and progression of liver diseases, such as alcohol‐associated liver disease, nonalcoholic fatty liver disease, cholestatic liver disease, hepatitis, cirrhosis, and hepatocellular carcinoma. Possible therapeutic implications based on modulation of signals transduction between the nervous system and the liver are also discussed. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fatty acids are involved in some hepatic disorders. The proprotein convertase subtilisin kexin 9 (PCSK9) inhibits the uptake of low-density lipoproteins (LDLs), which contain lipids, into the liver and may thus be associated with nonalcoholic fatty liver disease (NAFLD), a cardiovascular disorder (CVD) risk. Statins reduce blood LDL–cholesterol (LDL-C) levels and CVD risk and can attenuate the development of NAFLD while increasing blood PCSK9 levels. Methods: We investigated the correlation between PCSK9 and liver conditions in patients with familial hypercholesterolemia (FH), a CVD risk population with elevated blood LDL-C levels, under statin treatment. Blood tests for lipids, PCSK9, and liver function (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were performed in patients with FH taking statins (n = 25, mean age = 57 years, 12% of males). The ALT:AST ratio was used as a marker of NAFLD risk. Results: The mean LDL-C level was 3.38 mmol/L, and the median PCSK9 level was 312 ng/mL. The median ALT:AST ratio was 0.88. A significant negative correlation was observed between the PCSK9 and ALT:AST ratio (β = −0.67, p < 0.05). Conclusions: Their negative correlation might give a hypothetical insight into the effect of statin treatment on the development of NAFLD, in relation to PCSK9 behavior, in patients with FH. [ABSTRACT FROM AUTHOR]

Citrin deficiency (CD) is a complex metabolic condition due to defects in SLC25A13 encoding citrin, an aspartate/glutamate carrier located in the mitochondrial inner membrane. The condition was first described in Japan and other East Asian countries in patients who were thought to suffer from classical citrullinemia type 1, and was therefore classified as a urea cycle disorder. With an improved understanding of its molecular basis, it became apparent that a defect of citrin is primarily affecting the malate–aspartate shuttle with however multiple secondary effects on many central metabolic pathways including glycolysis, gluconeogenesis, de novo lipogenesis and ureagenesis. In the meantime, it became also clear that CD must be considered as a global disease with patients identified in many parts of the world and affected by SLC25A13 genotypes different from those known in East Asian populations. The present short review summarizes the (hi)story of this complex metabolic condition and tries to explain the relevance of including CD as a differential diagnosis in neonates and infants with cholestasis and in (not only adult) patients with hyperammonemia of unknown origin with subsequent impact on the emergency management. [ABSTRACT FROM AUTHOR]

Background: Changes in normal liver lipid levels indicate various diseases closely related to dietary and lifestyle factors. Magnetic resonance spectroscopy (MRS) is a reliable, advanced, and noninvasive method for estimating these levels. This study aimed to evaluate the interaction effect of diet and lifestyle factors on liver lipid levels, as measured by MRS, among female students. Methods and Results: This cross-sectional study included 29 female students from the Department of Radiological Sciences who underwent MRS to evaluate liver lipid levels and correlate these levels with lifestyle factors assessed by a questionnaire. SPSS two-way ANCOVA was applied to the acquired data. Diet and exercise had a significant interaction effect on the liver lipid levels after adjusting for gender and age (P=0.036). The interaction between diet and other factors such as caffeinated drinks, family history, smoking, and body mass index (BMI) with lipid levels did not reach significant levels (P>0.05). Conclusion: The results obtained support the strong interaction effect of diet and exercise on liver fat levels. Adopting a healthy lifestyle characterized by healthy food choices and regular exercise may help maintain normal liver fat levels and reduce the risk of HS and NAFLD in young women.

Abstract Background Fatty liver disease (FLD) is the common metabolic disease of liver with high worldwide prevalence. Nonalcoholic FLD may progress to acute hepatitis, chronic liver disease and even into hepatocellular carcinoma. Noninvasive parameters based on diagnostic imaging should be sought as the only diagnostic test available for this condition is liver biopsy. Objectives The objectives of this study are to correlate abdominal adiposity indicators, specifically visceral adipose tissue (VAT) thickness and subcutaneous adipose tissue (SAT) thickness, with body mass index (BMI) and fatty liver disease (FLD) grades using ultrasound, and to evaluate the diagnostic ability of the parameter "VAT thickness of 3 cm or above" in detecting hepatic steatosis. Method Total 100 patients were examined by ultrasound to evaluate VAT, SAT and FLD grades. All patients showing findings of steatotic liver were considered as cases and those showing normal liver findings were considered as controls. Correlation coefficient for VAT, SAT, BMI and FLD grades were calculated and p-value was derived. Sensitivity, Specificity, ROC curve and AUC value for parameter “VAT thickness 3 cm or above” was calculated. Results A total of 100 patients were examined including 33 males and 67 females. The mean age of patients was 42.34 ± 12.87 years. Mean VAT thicknesses was 3.69 ± 1.61 cm. The mean SAT thickness was 2.00 ± 0.86 cm. Mean BMI was 25.28 ± 5.13 kg/m2 (Overweight). Positive correlation of VAT and SAT measurements seen with BMI and FLD grades.” VAT thickness 3 cm or above”, to detect FLD has a good diagnostic ability with Sensitivity (95%), Specificity (96%), PPV (95%), NPV (96%) and area of curve value 0.8 to detect FLD. Conclusion The abdominal fat indicators were positively correlated with BMI and FLD grades. The parameter “VAT thickness 3 cm or above” has a good diagnostic efficacy to detect FLD and may be utilized as an alternative to liver biopsy.

Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) affects up to one-third of the global population. Since no approved pharmacotherapy for MAFLD is available, lifestyle modification remains the cornerstone of clinical care. Our study aims to evaluate the association of an overall healthy lifestyle with MAFLD risk. Methods We conducted an analysis of 327,387 participants from UK biobank. An overall healthy lifestyle score including six evidence-based lifestyles (diet, alcohol consumption, physical activity, sedentary behavior, sleep, and smoking) was assessed by questionnaires. MAFLD and its subtypes were diagnosed by blood biochemistry, ICD codes, and medication information from touchscreen and verbal interview. The prevalence ratios (PRs) and risk ratios (RRs) were estimated by Poisson regression models with robust variance. Results In the cross-sectional analysis, the PR (95% CI) was 0.83 (0.83 to 0.84) for MAFLD, and 0.83 (0.83 to 0.84) for MAFLD-overweight/obesity (MAFLD-O), 0.68 (0.66 to 0.70) for MAFLD-lean/normal weight and metabolic dysfunction (P-value for heterogeneity

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) incidence is increasing and correlated with metabolic dysfunction-associated steatotic liver disease (MASLD; formerly nonalcoholic fatty liver disease), even in patients without advanced liver fibrosis who are more likely to be diagnosed with advanced disease stages and shorter survival time, and less likely to receive a liver transplant. Machine learning (ML) tools can characterize large datasets and help develop predictive models that can calculate individual HCC risk and guide selective screening and risk mitigation strategies. METHODS: Tableau and KNIME Analytics were used for descriptive analytics and ML tasks. ML models were developed using standard laboratory and clinical parameters. Sci-kit learn algorithms were used for model development. Data from University of California (UC), Davis, were used to develop and train a pilot predictive model, which was subsequently validated in an independent dataset from UC San Francisco. MASLD and HCC patients were identified by International Classification of Diseases-9/10 codes. RESULTS: Of the patients diagnosed with MASLD (n = 1561 training; n = 686 validation), HCC developed in 14% (n = 227) of the UC Davis training cohort and 25% (n = 176) of the UC San Francisco validation cohort. Liver fibrosis determined by the noninvasive Fibrosis-4 score was the strongest single predictor for HCC in the model. Using the validation cohort, the model predicted HCC development at 92.06% accuracy with an area under the curve of 0.97, F1-score of 0.84, 98.34% specificity, and 74.41% sensitivity. CONCLUSION: ML models can aid physicians in providing early HCC risk assessment in patients with MASLD. Further validation will translate to cost-effective, personalized care of at-risk patients.

Summary: Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is on rise, in parallel with the increase in obesity and other lifestyle factors. The systematization of nutritional care is an important tool for diagnosing and intervening appropriately in these cases. However, despite the numerous interventions for MAFLD, few studies explore the systematized approach of the Nutrition Care Process. Objective: To identify the diagnosis and interventions in the nutritional care of people with non-alcoholic hepatic steatosis disease. Method: Descriptive cross-sectional study, of adults with non-alcoholic hepatic steatosis disease who were treated at a specialized outpatient clinic in a public hospital in southern Brazil. Data was collected from February to August 2023, with sociodemographic and clinical data supporting the diagnoses and nutritional interventions. The data was analyzed descriptively by central tendency, simple and relative frequency. Results: 45 people took part, most of them elderly (78%) and obese (93%). The most frequent nutritional problem was excessive energy (62%) and carbohydrate (57%) intake. The main goals set were to reduce energy and simple carbohydrate intake and increase fiber. Conclusion: The most common nutritional diagnosis was Excessive Expected Energy Intake and the need for interventions to reduce energy intake, simple carbohydrates and increase fiber, and all patients required nutritional monitoring. The systematization proposed in the Nutrition Care process standardizes the identification of the diagnosis and appropriate nutritional intervention, making it possible to monitor and evaluate the management of results.

Abstract Background Metabolic dysfunction-associated steatotic liver (MASLD) disease is the commonest hepatic cause of liver fibrosis and cirrhosis after the introduction of the direct acting antivirals and eradication of hepatitis C. MASLD is usually associated with metabolic syndrome and elevated inflammatory markers. Magnetic resonance spectroscopy (MRS) offers a non-invasive diagnostic, alternative to liver biopsy. This is a case–control diagnostic-accuracy study conducted on 40 patients in the Hepato-gastroenterology Unit in the Internal Medicine Department, Ain Shams University Hospitals, to study the role of MRI spectroscopy as a new diagnostic model for assessment of liver steatosis in non-diabetic MASLD patients compared to the standard ultrasound and clinical criteria. MASLD was diagnosed by a combination of a validated ultrasound hepatic steatosis score grading system and hepatic steatosis index using clinical and laboratory parameters. MRS was performed in all patients and fat peak, water peak, and fat fraction % were measured, and diagnostic accuracy of different MRS is compared to the US scoring and different laboratory and clinical parameters. To our knowledge this is the first study conducted on MRS in our region and Egypt. Results This study revealed no statistically significant difference between the two groups regarding HbA1C, creatinine, while there was highly statistically significant difference regarding fasting blood sugar, 2 h post-prandial glucose level, urine albumin, and low-density lipoprotein levels. Hepatic steatosis score grading by abdominal ultrasound on the 20 controls showed no fatty changes with grade 0 (50%), and on the 20 MASLD patients showed that 2 cases were grade 1 steatosis (5%), 9 cases were grade 2 steatosis (22.5%), and 9 cases were grade 3 steatosis (22.5%). The diagnostic accuracy of predicting hepatic steatosis using different MRS parameters: fat peak, water peak, and fat fraction had area under the curve of 99.9%, 88.6%, and 100%, respectively. The sensitivity and specificity of fat fraction in detecting hepatic steatosis were 100%. The sensitivity and specificity of the fat peak in detecting hepatic steatosis were 100% and 95%, respectively. Moreover, the sensitivity and specificity of the water peak in detecting the hepatic steatosis were 88.6% and 85%, respectively. There is a statistically significant correlation between the three MRS parameters and the abdominal ultrasound hepatic steatosis score grades. Conclusion MRS parameters: fat fraction, fat peak, and water peak, have high diagnostic accuracy for predicting the liver steatosis. Moreover, MRS has the added advantage of being a non-invasive and a tool with low radiation risk. MRS also shows the metabolic changes in the liver and could be an eligible outcome in therapeutic clinical trials.

Abstract The influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on gallbladder polyp development in both sexes remains elusive. Therefore, to clarify the role of MASLD in gallbladder polyp development, we investigated the longitudinal association between MASLD and gallbladder polyps. In this observational study, we included 5,527 gallbladder polyp-free patients who underwent > 2 health check-ups over > 2 years. Generalized estimation equations were used to analyze associations between MASLD and gallbladder polyp development according to repeated measures at baseline and the most recent stage. Gallbladder polyp development rates in men and women were 7.5% and 5.6% (p

The efficacy of artificial neural network (ANN) models employing laboratory variables for predicting fatty liver disease (FLD) remains inadequately established. The study aimed to develop ANN models to precisely predict FLD.

Aim: creation of diagnostic models including electrical, viscoelastic parameters of erythrocytes to distinguish fatty liver disease of mixed etiology (metabolic + alcoholic) from non-alcoholic and alcoholic fatty liver disease.Materials and methods. We examined 46 men with non-alcoholic fatty liver disease (NAFLD), 43 men with alcoholic fatty liver disease (AFLD), as well as 54 men with fatty liver disease (FLD) of mixed genesis (metabolic + alcohol-related); average age of the patients included in the study made 48.4 ± 9.6 years. The diagnosis was established on the basis of liver ultrasound findings and FLI liver steatosis index with a fibrosis grade of F1 or less (FibroScan® 502, Echosens, France). The electrical and viscoelastic parameters of erythrocytes were investigated by the diagnostic technique of dielectrophoresis using an electrooptical cell detection system.Results. The most significant parameters for differentiating fatty liver disease of mixed genesis (metabolic + alcoholic) from NAFLD using the Volcano plot have turned out to be cell polarizability at a frequency of 106 Hz (p = 6.49 ×10-5), erythrocyte cell membrane capacity (p = 0.00077), relative polarizability (p = 0.001), the levels of which were higher in patients with NAFLD. On the contrary, the index of red blood cells destruction at 105 Hz was higher in FLD of the mixed genesis (p = 0.047) and the crossover frequency was shifted to the high frequency range more than in NAFLD (p = 0.0005). The discriminant analysis has additionally revealed the significance of the degree of erythrocyte deformation at 5 ×105 Hz in distinguishing between mixed-genesis FLD and NAFLD. In differentiating FLD of mixed genesis from NAFLD, a diagnostic model incorporating the above red blood cells parameters has provided an AUC of 0.829 (confidential interval: 0.742–0.916), sensitivity of 80.9 %, and specificity of 83.3 %. Two indicators of red blood cells have been established that statistically significantly distinguish the mixed-genesis FLD from the AFLD (Volcano plot); these are the index of red blood cells destruction at a frequency of 5 ×105 Hz, which was higher with AFLD (p = 0.0007), and the capacity of cell membranes, the value of which prevailed in mixed-genesis FLD (p = 0.011). When distinguishing the mixed-genesis FLD from the AFLD, the combined model with the inclusion of three parameters of red blood cells, namely the index of red blood cells destruction at a frequency of 5 ×105 Hz, the capacity of erythrocyte membranes, and polarizability at a frequency of 106 Hz, has shown the highest levels of diagnostic accuracy, namely AUC = 0.751 (confidential interval: 0.611–0.908) with a sensitivity of 79.5 %, specificity of 74.7 %.Conclusion. The electrical and viscoelastic parameters of erythrocytes studied using the diagnostic technique of dielectrophoresis should be considered as promising biomarkers for the diagnosis of diffuse liver disease.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of hepatocellular carcinoma (HCC) worldwide. Over the years, Perilipin 5 (PLIN5) has been recognized as a key regulator of both MAFLD and HCC development. In our previous studies we demonstrated that deficiency in Plin5 reduces the severity of MAFLD and HCC in mice. Interestingly, it has been established that patients with MAFLD and HCC exhibit various changes in their gut microbiome profiles. The gut microbiome itself has been shown to play a role in modulating carcinogenesis and the immune response against cancer. Methods: Therefore, we conducted a study to investigate the alterations in fecal microbiome composition in wild type (WT) and Plin5-deficient (Plin5-/-) mice models of MAFLD and MAFLD-induced HCC (MAFLD-HCC). We utilized 16S rRNA gene sequencing analysis to profile the composition of gut bacteria in fecal samples. Results: Notably, we discovered that the absence of Plin5 alone is already associated with changes in gut microbiota composition. Moreover, feeding the mice a Western diet (WD) resulted in additional microbial alterations. Interestingly, Plin5-/- animals exhibited an enrichment of the beneficial taxa Lactobacillus in both animal models. Discussion: Our findings identify Plin5 as a major regulator of gut microbiota during the development of MAFLD and MAFLD-HCC. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) is spreading worldwide, largely due to unhealthy lifestyles that contribute to the rise in diabetes, metabolic syndrome, and obesity. In this situation, the progression of injury to metabolic steatohepatitis can evolve to cirrhosis and, eventually, to hepatocellular carcinoma (HCC). It is well known that serine protease enzymes with different functions in cellular homeostasis act as signaling molecules that regulate liver inflammation by activating the protease-activated receptors (PARs) family members, expressed on the cellular plasma membrane. Among them, PAR2 plays a central role in the activation of signaling pathways in response to changes in the extracellular microenvironment. Experimental data have provided evidence that PAR2 is involved not only in inflammatory response but also in insulin resistance, lipid metabolism, and cancer. The major aims of this narrative review are addressed to assess PAR2 involvement in inflammation, metabolism, and liver disease progression and to explore possible therapeutic strategies, based on PAR2 inhibition, in order to prevent its biological effects in the context of MAFLD and cancer. [ABSTRACT FROM AUTHOR]

The historical use of the term non-alcoholic fatty liver disease (NAFLD) in obese/overweight children has been controversial as to the appropriateness of this terminology in children, and lately, in adults too. Newer game-changer terminology, metabolic (dysfunction)-associated fatty liver disease (MAFLD), for this condition signifies a positive step forward that addresses the limitations of the previous definition for both adults and children. The prevalence of MAFLD has surged in tandem with the global rise in obesity rates, establishing itself as a predominant cause of chronic liver disease in both adult and pediatric populations. The adoption of the recently proposed nomenclature reflects a more encompassing comprehension of the disease and its etiology compared to its predecessor, NAFLD. Notably, the revised terminology facilitates the recognition of MAFLD as an autonomous condition while acknowledging the potential coexistence of other systemic fatty liver disorders. Particularly in children, this includes various paediatric-onset genetic and inherited metabolic disorders, necessitating thorough exclusion, especially in cases where weight loss interventions yield no improvement or in the absence of obesity. MAFLD presents as a multifaceted disorder; evidence suggests its origins lie in a complex interplay of nutritional, genetic, hormonal, and environmental factors. Despite advancements, current non-invasive diagnostic biomarkers exhibit limitations in accuracy, often necessitating imaging and histological evaluations for definitive diagnosis. While dietary and lifestyle modifications stand as cornerstone measures for MAFLD prevention and management, ongoing evaluation of therapeutic agents continues. This article provides an overview of the latest developments and emerging therapies in the realm of paediatric MAFLD. [ABSTRACT FROM AUTHOR]

Chronic Kidney Disease (CKD) is a condition of gradual or chronic decline in kidney function, which is quite severe and caused by various kidney diseases, including urinary obstruction. This disease is progressive and generally irreversible. CKD requires kidney replacement therapy, one of which is continuous ambulatory peritoneal dialysis (CAPD). To determine the prevalence and risk factors for End Stage Renal Disease (ESRD) in patients undergoing CAPD due to urinary obstruction. We performed a retrospective cohort with a cross-sectional study was conducted using secondary data from medical record data of ESRD patients with CAPD accompanied by urinary obstruction at Dr. Saiful Anwar General Hospital, Malang, Indonesia. The prevalence of CKD in patients with CAPD accompanied by urinary obstruction was 6,50% and dominated by males (57,8%) with an age range of 41-50 years (26%). The majority of comorbidities are severely high the Body Mass Index (BMI) (89,0%) and hypertension (80,8%). The location of obstruction is mostly unilateral (5,64%) with mild levels (4,06%). Urinary obstruction is a frequent clinical finding in CKD patients with CAPD. The most common risk factor in this study was hypertension. The prevalence and comorbidities among CAPD patients with Urinary obstruction (UO) are better understood because to this study. It is necessary to recognise its limitations, particularly the small sample size and single-centre design. Future studies should involve more centres and larger patient groups in order to provide a more thorough knowledge of the mechanisms behind the high survival rates among CAPD patients. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a condition marked by excessive fat accumulation in the liver and poses a significant health challenge. The leaves of Blumea balsamifera and Sargassum aquifolium have been reported to have anti-atherogenic effects. This study aims to determine the effectiveness of B. balsamifera extract (BBLE) and S. aquifolium extract (SAE) in preventing and treating liver fat accumulation in Wistar rats induced by a high-cholesterol diet through the expression of the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRTl)/peroxisome proliferator-activated receptor y (PPARy) pathway, and the leptin receptor. The experimental design of this study is laboratory-based, involving, 20 Wistar rats were fed a high-cholesterol diet over a period of 21 days. The rats were divided into four groups for the evaluation of BBLE and SAE effect: negative control (P0): induced with a high-cholesterol diet + distilled water, positive control (Pl): induced with a high-cholesterol diet + simvastatin, P2: induced with a highcholesterol diet + 4 mg/kg/bw BBLE, and P3: induced with a highcholesterol diet + 4 mg/kg/bw BBLE and 4 mg/kg/bw SAE. The treatment duration extended over three months. Immunohistochemical analyses were performed on liver tissues to measure AMPK, SIRT1, PPARy, and leptin receptor expression. The results indicated that leptin expression was lower in the BBLE+SAE group compared to the simvastatin group, and differences were significant between the BBLE and BBLE+SAE groups. No significant differences were noted in AMPK, SIRT1, and PPARy expression between the simvastatin and BBLE+SAE groups (p>0.05). In conclusion, BBLE and SAE effectively reduce liver lipid accumulation and enhance fat metabolism in hypercholesterolemic rats. [ABSTRACT FROM AUTHOR]

The inhibitor-kappaB kinase epsilon (IKKε) represents a non-canonical IκB kinase that modulates NF-κB activity and interferon I responses. Inhibition of this pathway has been linked with atherosclerosis and metabolic dysfunction-associated steatotic liver disease (MASLD), yet the results are contradictory. In this study, we employed a combined model of hepatic PCSK9D377Y overexpression and a high-fat diet for 16 weeks to induce atherosclerosis and liver steatosis. The development of atherosclerotic plaques, serum lipid concentrations, and lipid metabolism in the liver and adipose tissue were compared between wild-type and IKKε knock-out mice. The formation and progression of plaques were markedly reduced in IKKε knockout mice, accompanied by reduced serum cholesterol levels, fat deposition, and macrophage infiltration within the plaque. Additionally, the development of a fatty liver was diminished in these mice, which may be attributed to decreased levels of multiple lipid species, particularly monounsaturated fatty acids, triglycerides, and ceramides in the serum. The modulation of several proteins within the liver and adipose tissue suggests that de novo lipogenesis and the inflammatory response are suppressed as a consequence of IKKε inhibition. In conclusion, our data suggest that the knockout of IKKε is involved in mechanisms of both atherosclerosis and MASLD. Inhibition of this pathway may therefore represent a novel approach to the treatment of cardiovascular and metabolic diseases. [ABSTRACT FROM AUTHOR]

Introduction: Ginseng berry (GB) has previously been demonstrated to improve systemic insulin resistance and regulate hepatic glucose metabolism and steatosis in mice with diet-induced obesity (DIO). Objectives: In this study, the role of GB in metabolism was assessed using metabolomics analysis on the total liver metabolites of DIO mice. Methods: Metabolomic profiling was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF/MS) of liver tissue from mice on a 12-wk normal chow diet (NC), high-fat diet (HFD), and HFD supplemented with 0.1% GB (HFD + GB). The detected metabolites, its pathways, and functions were analyzed through partial least square discriminant analysis (PLS-DA), the small molecular pathway database (SMPDB), and MetaboAnalyst 5.0. Results: The liver metabolite profiles of NC, HFD, and GB-fed mice (HFD + GB) were highly compartmentalized. Metabolites involved in major liver functions, such as mitochondrial function, gluconeogenesis/glycolysis, fatty acid metabolism, and primary bile acid biosynthesis, showed differences after GB intake. The metabolites that showed significant correlations with fasting blood glucose (FBG), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were highly associated with mitochondrial membrane function, energy homeostasis, and glucose metabolism. Ginseng berry intake increased the levels of metabolites involved in mitochondrial membrane function, decreased the levels of metabolites related to glucose metabolism, and was highly correlated with metabolic phenotypes. Conclusion: This study demonstrated that long-term intake of GB changed the metabolite of hepatosteatotic livers in DIO mice, normalizing global liver metabolites involved in mitochondrial function and glucose metabolism and indicating the potential mechanism of GB in ameliorating hyperglycemia in DIO mice. [ABSTRACT FROM AUTHOR]

Background: Hepatic steatosis is characterized by lipid accumulation in hepatocytes. Cheong-sang-gyeon-tong-tang is a major prescription for all types of headaches in traditional East Asian medicine. Objective: This study aimed to investigate the pharmacological effects of Cheong-sang-gyeon-tong-tang extract (CG) on high-fat diet (HFD)-induced hepatic steatosis in mice and to explore the underlying mechanism. Results: Treatment with CG significantly reduced body weight, liver weight, and epididymal fat mass, as well as improved the serum and hepatic lipid profiles in the HFD-induced fatty liver mouse model. Further, CG alleviated lipid accumulation in HFD-fed mice by controlling lipid metabolism, including triglyceride and cholesterol synthesis, and fatty acid oxidation at the mRNA level. CG also regulated the expression of cholesterol regulatory proteins in HFD-induced fatty liver mice. Conclusions: These results indicate that CG alleviates hepatic steatosis by regulating cholesterol homeostasis in HFD-induced fatty liver mice, thus improving our understanding of the mechanisms by which CG improves hepatic steatosis. Therefore, we propose CG as a therapeutic candidate for lipid metabolic disorders such as fatty liver disease. [ABSTRACT FROM AUTHOR]

Justification: There has been an alarming increase in metabolic dysfunction-associated steatotic liver disease (MASLD) and it is now the most common chronic liver disease worldwide, in both adult and pediatric populations. The lack of regional guidelines has hampered the formulation of national policies for prevention and management of MASLD in children. Therefore, we formulated recommendations for steatotic liver disease in children. Objectives: To review the existing literature on the burden and epidemiology of pediatric MASLD and formulate recommendations for diagnostic evaluation, prevention, and management strategies. Process: The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international stakeholders to participate in a consensus meeting held on April 20, 2024, in Mumbai, Maharashtra, India. Various aspects of pediatric steatotic liver disease were deliberated upon and a consensus document and recommendations were formulated after several rounds of discussion. Recommendations: Metabolic dysfunction-associated steatotic liver disease (MASLD) should be used as the preferred term in place of non-alcoholic fatty liver disease (NAFLD). There is a high prevalence of steatotic liver disease (SLD) among Indian children and adolescents, especially those who are overweight or obese. This condition may be progressive in childhood and associated with increased morbidity and mortality in adulthood. Various lifestyle, dietary, and genetic factors may predispose individuals to MASLD, including an increased intake of calorie-dense processed foods, sweetened sugar beverages, excessive screen time, higher sedentary time and lack of moderate to vigorous physical activity. MASLD is usually asymptomatic or presents with mild, non-specific symptoms and therefore, a high degree of suspicion is required for early diagnosis. MASLD is usually associated with cardiometabolic factors (hypertension, insulin resistance/diabetes mellitus, and/or dyslipidemia) and secondary causes should be excluded in all cases, particularly in the presence of red flag signs. Screening for MASLD should be considered in all obese children (body mass index or BMI ≥ 95th percentile) and in all overweight children (BMI ≥ 85th and <95thpercentile) with additional risk factors, such as prediabetes/diabetes, dyslipidemia, positive family history of metabolic syndrome, obstructive sleep apnea, and hypopituitarism. Abdominal ultrasound in combination with alanine aminotransferase (ALT) levels should be used as a screening test for MASLD in Indian children as per the proposed algorithm. Diet (any hypocaloric diet) and exercise (aerobic, resistance, or a combination of both; moderate to high intensity; regular in frequency) remain the cornerstones of pediatric MASLD management. Pharmacotherapy and/or endoscopic/surgical techniques for obesity should be considered as adjuncts and should be considered only after a failed adequate trial of lifestyle modifications. [ABSTRACT FROM AUTHOR]

The influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on gallbladder polyp development in both sexes remains elusive. Therefore, to clarify the role of MASLD in gallbladder polyp development, we investigated the longitudinal association between MASLD and gallbladder polyps. In this observational study, we included 5,527 gallbladder polyp-free patients who underwent > 2 health check-ups over > 2 years. Generalized estimation equations were used to analyze associations between MASLD and gallbladder polyp development according to repeated measures at baseline and the most recent stage. Gallbladder polyp development rates in men and women were 7.5% and 5.6% (p < 0.01), respectively. MASLD was not significantly correlated with gallbladder polyp development. Regarding the association between gallbladder polyp development (men: ≥6 mm and women: ≥5 mm) and the number of MASLD components following lifestyle habits, men and women with ≥ 4 MASLD components had odds ratios of 3.397 (95% confidence interval: 1.096–10.53) and 5.338 (1.054–27.04), respectively. Higher nonalcoholic fatty liver disease fibrosis scores were associated with significant risk of gallbladder polyp development in women (1.991, 1.047–3.785). Although MASLD influence on gallbladder polyp development differs by sex, close monitoring of patients with an increasing number of MASLD components is essential to prevent gallbladder polyp development. Specifically, men with ≥ 4 MASLD components should be monitored for gallbladder polyps measuring ≥ 6 mm. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver (MASLD) disease is the commonest hepatic cause of liver fibrosis and cirrhosis after the introduction of the direct acting antivirals and eradication of hepatitis C. MASLD is usually associated with metabolic syndrome and elevated inflammatory markers. Magnetic resonance spectroscopy (MRS) offers a non-invasive diagnostic, alternative to liver biopsy. This is a case–control diagnostic-accuracy study conducted on 40 patients in the Hepato-gastroenterology Unit in the Internal Medicine Department, Ain Shams University Hospitals, to study the role of MRI spectroscopy as a new diagnostic model for assessment of liver steatosis in non-diabetic MASLD patients compared to the standard ultrasound and clinical criteria. MASLD was diagnosed by a combination of a validated ultrasound hepatic steatosis score grading system and hepatic steatosis index using clinical and laboratory parameters. MRS was performed in all patients and fat peak, water peak, and fat fraction % were measured, and diagnostic accuracy of different MRS is compared to the US scoring and different laboratory and clinical parameters. To our knowledge this is the first study conducted on MRS in our region and Egypt. Results: This study revealed no statistically significant difference between the two groups regarding HbA1C, creatinine, while there was highly statistically significant difference regarding fasting blood sugar, 2 h post-prandial glucose level, urine albumin, and low-density lipoprotein levels. Hepatic steatosis score grading by abdominal ultrasound on the 20 controls showed no fatty changes with grade 0 (50%), and on the 20 MASLD patients showed that 2 cases were grade 1 steatosis (5%), 9 cases were grade 2 steatosis (22.5%), and 9 cases were grade 3 steatosis (22.5%). The diagnostic accuracy of predicting hepatic steatosis using different MRS parameters: fat peak, water peak, and fat fraction had area under the curve of 99.9%, 88.6%, and 100%, respectively. The sensitivity and specificity of fat fraction in detecting hepatic steatosis were 100%. The sensitivity and specificity of the fat peak in detecting hepatic steatosis were 100% and 95%, respectively. Moreover, the sensitivity and specificity of the water peak in detecting the hepatic steatosis were 88.6% and 85%, respectively. There is a statistically significant correlation between the three MRS parameters and the abdominal ultrasound hepatic steatosis score grades. Conclusion: MRS parameters: fat fraction, fat peak, and water peak, have high diagnostic accuracy for predicting the liver steatosis. Moreover, MRS has the added advantage of being a non-invasive and a tool with low radiation risk. MRS also shows the metabolic changes in the liver and could be an eligible outcome in therapeutic clinical trials. [ABSTRACT FROM AUTHOR]

Background: Abnormal lipid deposition is an important driver of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). MicroRNA-411-5p (miR-411-5p) and eukaryotic translation initiation factor 4γ2 (EIF4G2) are related to abnormal lipid deposition, but the specific mechanism is unknown. Methods: A high-fat, high-cholesterol diet (HFHCD) and a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) and a high-fructose diet (HFrD) were used to establish MASLD rat and mouse models, respectively. MiR-411-5p agomir and mimic were used to upregulate the miR-411-5p in vivo and in vitro, respectively. Adeno-associated virus type 8 (AAV8) carrying EIF4G2 short hairpin RNA (shRNA) and small interfering RNA (siRNA) were used to downregulate the EIF4G2 expression in vivo and in vitro, respectively. Liver histopathological analysis, Biochemical analysis and other experiments were used to explore the functions of miR-411-5p and EIF4G2. Results: MiR-411-5p was decreased in both MASLD rats and mice, and was negatively correlated with liver triglycerides and serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. Upregulation of miR-411-5p alleviated liver lipid deposition and hepatocellular steatosis. Moreover, miR-411-5p targeted and downregulated EIF4G2. Downregulation of EIF4G2 not only reduced liver triglycerides and serum ALT and AST levels in MASLD model, but also alleviated lipid deposition. Notably, upregulation of miR-411-5p and downregulation of EIF4G2 led to the reduction of forkhead box class O3 (FOXO3) and inhibited the expression of sterol regulatory-element binding protein 1 (SREBP1), acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), thereby reducing fatty acid synthesis. Conclusions: Upregulation of miR-411-5p inhibits EIF4G2 to reduce the FOXO3 expression, thereby reducing fatty acid synthesis and alleviating abnormal lipid deposition in MASLD. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence of IHD in patients of NAFLD. Study Design: Cross-sectional. Setting: Tertiary Care Hospital, Sargodha. Period: June 2022 to June 2023. Methods: The present research included sample size of 190 patients, who were checked for presence of IHD. Results: Overall prevalence of IHD among NAFLD patients was found to be 84.2%. Conclusion: NAFLD is associated with higher risk of IHD occurrence. [ABSTRACT FROM AUTHOR]

Aims: To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction‐associated steatotic liver disease (MASLD). Materials and Methods: In Part A (cross‐sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol−1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol−1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6‐week interventions: (1) exercise training (EX; 70%–75% maximum heart rate; four sessions/week; n = 13) or (2) non‐exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA‐IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin‐18 (CK18) M65, among others. Results: In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA‐IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = −0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433). Conclusions: Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate‐intensity exercise training. [ABSTRACT FROM AUTHOR]

Aim: To evaluate insulin and glucagon sensitivity in Han Chinese women with and without gestational diabetes mellitus (GDM). Methods: In total, 81 women with GDM and 81 age‐matched healthy controls were evaluated with a 75 g oral glucose tolerance test (OGTT) at gestational weeks 24‐28. Plasma glucose concentrations were measured at fasting and 1 h and 2 h post‐OGTT. Fasting plasma insulin, glucagon and amino acids were also measured. Insulin and glucagon sensitivity were assessed by the homeostatic model assessment of insulin resistance (HOMA‐IR) and glucagon‐alanine index, respectively. Results: As expected, plasma glucose concentrations were higher at fasting and 1 h and 2 h post‐OGTT in GDM participants (p <.001 each). Both the HOMA‐IR and the glucagon‐alanine index were higher in GDM participants. There was a weak positive correlation between HOMA‐IR and glucagon‐alanine index (r = 0.24, p =.0024). Combining the HOMA‐IR and the glucagon‐alanine index yielded better capacity (area under the curve = 0.878) than either alone (area under the curve = 0.828 for HOMA‐IR and 0.751 for glucagon‐alanine index, respectively) in differentiating GDM from healthy participants. While the majority of GDM participants (64%) exhibited both reduced insulin and glucagon sensitivity, a third of them presented either reduced insulin (20%) or glucagon (14%) sensitivity alone. HOMA‐IR and glucagon‐alanine index correlated differentially with fasting glucose, triglycerides, low‐density lipoprotein cholesterol, sum of amino acids and hepatic steatosis index. Conclusions: Impairments of both insulin and glucagon sensitivity occur frequently in Chinese women with GDM, which may, individually or together, drive metabolic derangements in GDM. These observations provide new insights into the pathophysiology of GDM and support the need to target insulin or glucagon resistance, or both, in the management of GDM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with obesity and, therefore, it is important to target both overweight and hyperglycaemia. Glucagon plays important roles in glucose, amino acid and fat metabolism and may also regulate appetite and energy expenditure. These physiological properties are currently being exploited therapeutically in several compounds, most often in combination with glucagon‐like peptide‐1 (GLP‐1) agonism in the form of dual agonists. With this combination, increases in hepatic glucose production and hyperglycaemia, which would be counterproductive, are largely avoided. In multiple randomized trials, the co‐agonists have been demonstrated to lead to significant weight loss and, in participants with T2DM, even improved glycated haemoglobin (HbA1c) levels. In addition, significant reductions in hepatic fat content have been observed. Here, we review and discuss the studies so far available. Twenty‐six randomized trials of seven different GLP‐1 receptor (GLP‐1R)/glucagon receptor (GCGR) co‐agonists were identified and reviewed. GLP‐1R/GCGR co‐agonists generally provided significant weight loss, reductions in hepatic fat content, improved lipid profiles, insulin secretion and sensitivity, and in some cases, improved HbA1c levels. A higher incidence of adverse effects was present with GLP‐1R/GCGR co‐agonist treatment than with GLP‐1 agonist monotherapy or placebo. Possible additional risks associated with glucagon agonism are also discussed. A delicate balance between GLP‐1 and glucagon agonism seems to be of particular importance. Further studies exploring the optimal ratio of GLP‐1 and glucagon receptor activation and dosage and titration regimens are needed to ensure a sufficient safety profile while providing clinical benefits. [ABSTRACT FROM AUTHOR]

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One of the challenges of modern-day living is to resist the temptation of overfeeding and sedentariness and maintain a healthy body and mind. On a favorable genetic and epigenetic background, a high-fat diet combined with lack of physical exercise constitutes the foundation for severe metabolic disturbances including steatotic liver disease. In our case-control study, we had the aim of establishing the role of selected micro-RNAs--miR-122, miR-192, miR-33a, and miR-33b--as superior biomarkers for the diagnosis and prognosis of steatotic liver in a 36-patient cohort compared to 12 healthy controls. Initial results confirmed the decline in miR-122 expression as fatty liver is progressing. However, combinations of DmiRs, such as DmiR33a_192, DmiR33a_122, and DmiR33b_122, correlate with ultrasound steatosis grade (R2 = 0.78) while others such as DmiR33b_122 provide a high specificity and sensitivity in fatty liver disease with an area under the curve (AUC) of 0.85. Compared to classical biomarkers, micro-RNAs can be used for both diagnostic and prognostic purposes as their diminished expression in severe cases of steatosis is associated with higher risk of emerging hepatocellular carcinoma. Manipulating micro-RNAs through agomirs or antagomirs can be the answer to the yet unsolved problem of efficient therapy in MAFLD. [ABSTRACT FROM AUTHOR]

Objectives: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally, with an estimated prevalence exceeding 25%. Variants in the PNPLA3 and HSD17B13 genes have been a focus of investigations surrounding the etiology and progression of NAFLD and are believed to contribute to a greater burden of disease experienced by Hispanic Americans. However, little is known about socioeconomic factors influencing NAFLD progression or its increased prevalence among Hispanics. Materials and Methods: We cross‐sectionally analyzed 264 patients to assess the role of genetic and socioeconomic variables in the development of advanced liver fibrosis in individuals at risk for NAFLD. Results: Adjusting for age, sex, body mass index, and PNPLA3 genotype, lacking a college degree was associated with 3.3 times higher odds of advanced fibrosis (95% confidence interval [CI]: 1.21–8.76, p = 0.019), an effect comparable to that of possessing the major PNPLA3 risk variant. Notably, the effect of PNPLA3 genotype on advanced fibrosis was attenuated to nonsignificance following adjustment for education and other socioeconomic markers. The effect of the protective HSD17B13 variant, moreover, diminished after adjustment for education (odds ratio [OR]: 0.39 [95% CI: 0.13–1.16, p = 0.092]), while lower education continued to predict advanced fibrosis following multivariable adjustment with an OR of 8.0 (95% CI: 1.91–33.86, p = 0.005). Discussion: Adjusting for education attenuated the effects of genotype and Hispanic ethnicity on liver fibrosis, suggesting that social factors—rather than genes or ethnicity—may be driving disease severity within some populations. Findings reveal the importance of including socioenvironmental controls when considering the role of genetics or ethnicity in complex disease. [ABSTRACT FROM AUTHOR]

Aim: In this study, we investigated glucose and lactate kinetics during a 75 g oral glucose tolerance test (OGTT) in 23 overweight and obese adolescents and assessed putative differences among participants with and without metabolic dysfunction‐associated steatotic liver disease (MASLD). Methods: We enrolled 23 young people (six girls) with obesity [body mass index 33 (29‐37)]. Glucose‐lactate kinetics parameters (disposal glucose insulin sensitivity, SID; fraction of glucose converted into lactate, fr; fractional lactate clearance rate, kL) and lactate production rate (LPR) were estimated using the oral glucose‐lactate minimal model. MASLD presence was assessed using the proton density fat fraction. We analysed glucose, lactate and LPR time to peak, peak values and area under the curve and evaluated differences using the Wilcoxon test. MASLD and no‐MASLD participants were compared using the Mann‐Whitney test. Correlations between parameters were assessed using the Spearman correlation coefficient (ρ). We also tested the performance of two (4 or 3 h OGTT) protocols in estimating oral glucose‐lactate minimal model and LPR parameters. Results: Glucose peaks 30 min earlier than lactate (p =.0019). This pattern was present in the no‐MASLD group (p <.001). LPR peaks 30 min later in the MASLD group (p =.02). LPR and kL were higher in MASLD, suggesting higher glycolysis and lactate utilization. SID and fr correlate significantly (ρ = −0.55, p =.008). SID and fr were also correlated with the body mass index, (ρ = −0.45, p =.04; and ρ = 0.45; p =.03). The protocol duration did not influence the estimates of the parameters. Discussion: Youth with MASLD showed a delayed glucose metabolism, possibly because of greater utilization of the underlying substrates. A 3‐h OGTT may be used to assess lactate metabolism effectively. [ABSTRACT FROM AUTHOR]

Purpose: Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. Materials and methods: Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan–Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. Results: 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32–3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58–2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52–3.16, p = 0.595) by log-rank analysis. Conclusion: TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction−associated liver disease (MASLD) and steatohepatitis (MASH) are becoming the most common causes of chronic liver disease in the United States and worldwide due to the obesity and diabetes epidemics. It is estimated that by 2030 close to 100 million people might be affected and patients with type 2 diabetes are especially at high risk. Twenty to 30% of patients with MASLD can progress to MASH, which is characterized by steatosis, necroinflammation, hepatocyte ballooning, and in advanced cases, fibrosis progressing to cirrhosis. Clinically, it is recognized that disease progression in diabetic patients is accelerated and the role of various genetic and epigenetic factors, as well as cell–matrix interactions in fibrosis and stromal remodeling, have recently been recognized. While there has been great progress in drug development and clinical trials for MASLD/MASH, the complexity of these pathways highlights the need to improve diagnosis/early detection and develop more successful antifibrotic therapies that not only prevent but reverse fibrosis. [ABSTRACT FROM AUTHOR]