Steatotic Livers Research Articles

S1944 Recruitment of Minority Patients in Metabolic Dysfunction-Associated Steatotic Liver Disease Clinical Trials

S1944 Recruitment of Minority Patients in Metabolic Dysfunction-Associated Steatotic Liver Disease Clinical Trials

S1883 Evaluating Differences in Screening Between Pediatric and Adult Patients for Development of Metabolic Dysfunction-Associated Steatotic Liver Disease at an Academic Primary Care Clinic

S1883 Evaluating Differences in Screening Between Pediatric and Adult Patients for Development of Metabolic Dysfunction-Associated Steatotic Liver Disease at an Academic Primary Care Clinic

The Interplay between Liver and Adipose Tissue in the Onset of Liver Diseases: Exploring the Role of Vitamin Deficiency.

The deficiency of vitamins, a condition known as "hidden hunger", causes comprehensive pathological states. Research over the years has identified a relationship between liver diseases and hypovitaminosis or defects in vitamin metabolism. The exact mechanisms remain elusive; however, the crucial involvement of specific vitamins in metabolic functions, alongside the reclassification of liver disease as metabolic dysfunction-associated steatotic liver disease (MASLD), has prompted researchers to investigate the potential cause-effect dynamics between vitamin deficiency and liver disease. Moreover, scientists are increasingly investigating how the deficiency of vitamins might disrupt specific organ crosstalk, potentially contributing to liver disease. Although the concept of a dysmetabolic circuit linking adipose tissue and the liver, leading to liver disease, has been discussed, the possible involvement of vitamin deficiency in this axis is a relatively recent area of study, with numerous critical aspects yet to be fully understood. In this review, we examine research from 2019 to July 2024 focusing on the possible link between liver-adipose tissue crosstalk and vitamin deficiency involved in the onset and progression of non-alcoholic fatty liver disease (NAFLD). Studies report that vitamin deficiency can affect the liver-adipose tissue axis, mainly affecting the regulation of systemic energy balance and inflammation.

Association between antibiotic use and cardiovascular diseases in metabolic dysfunction-associated steatotic liver disease: A nationally representative retrospective cohort study.

Various subcategories for steatotic liver disease (SLD) were proposed globally. Previous studies suggested a heightened risk of cardiovascular diseases (CVD) with prolonged antibiotic exposure and metabolic dysfunction-associated SLD (MASLD), respectively. This study investigates the impact of antibiotic usage on CVD in MASLD patients. From the Korean National Health Insurance Service database, 276520 adults aged 40 and older were included. Antibiotic exposure was defined by the cumulative prescription days and the number of classes. Participants were categorized into no SLD and MASLD groups. Hepatic steatosis was defined by using the fatty liver index ≥60. From 2013 to 2019, 16197 CVD cases were recorded. A multivariate Cox model, adjusting for covariates, assessed adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD risk associated with MASLD and antibiotic prescriptions. The group with ≥91days of antibiotics prescribed and MASLD showed a significantly increased risk of CVD (aHR, 1.56; 95% CI, 1.39-1.74) compared with antibiotic non-users without SLD. Furthermore, the group with ≥4 classes of antibiotics prescribed and MASLD had an elevated risk of CVD (aHR, 1.49; 95% CI,1.34-1.66) compared with antibiotic non-users without SLD. Consistent results were observed in several sensitivity analyses. Our study identified prolonged antibiotic exposure may be a factor that increases the risk of CVD in MASLD patients. These findings suggest an epidemiological basis for the therapeutic application of antibiotics in MASLD patients, and emphasize the need for further studies to deepen the understanding of these intricate relationships.

Comparative efficacy of THR-β agonists, FGF-21 analogues, GLP-1R agonists, GLP-1-based polyagonists, and Pan-PPAR agonists for MASLD: A systematic review and network meta-analysis

AimsTo compare the efficacy of thyroid hormone receptor beta (THR-β) agonists, fibroblast growth factor 21 (FGF-21) analogues, glucagon-like peptide-1 receptor agonists (GLP-1RAs), GLP-1-based polyagonists, and pan-peroxisome proliferator-activated receptor (Pan-PPAR) agonists in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). MethodsA database search for relevant randomized double-blind controlled trials published until July 11, 2024, was conducted. Primary outcomes were the relative change in hepatic fat fraction (HFF) and liver stiffness assessed non-invasively by magnetic resonance imaging proton density fat fraction and elastography. Secondary outcomes included histology, liver injury index, lipid profile, glucose metabolism, blood pressure, and body weight. ResultsTwenty-seven trials (5357 patients with MASLD) were identified. For HFF reduction, GLP-1-based polyagonists were most potentially effective (mean difference [MD] −51.47; 95 % confidence interval [CI]: −68.25 to −34.68; surface under the cumulative ranking curve [SUCRA] 84.9) vs. placebo, followed by FGF-21 analogues (MD −47.08; 95 % CI: −58.83 to −35.34; SUCRA 75.5), GLP-1R agonists (MD −37.36; 95 % CI: −69.52 to −5.21; SUCRA 52.3) and THR-β agonists (MD −33.20; 95 % CI: −43.90 to −22.51; SUCRA 36.9). For liver stiffness, FGF-21 analogues were most potentially effective (MD −9.65; 95 % CI: −19.28 to −0.01; SUCRA 82.2) vs. placebo, followed by THR-β agonists (MD −5.79; 95 % CI: −9.50 to −2.09; SUCRA 58.2), and GLP-1RAs (MD −5.58; 95 % CI: −15.02 to 3.86; SUCRA 54.7). For fibrosis improvement in histology, GLP-1-based polyagonists were most potentially effective, followed by FGF-21 analogues, THR-β agonists, Pan-PPAR agonists, and GLP-1R agonists; For MASH resolution in histology, GLP-1-based polyagonists were most potentially effective, followed by THR-β agonists, GLP-1R agonists, FGF-21 analogues, and Pan-PPAR agonists. THR-β agonists are well-balanced in liver steatosis and fibrosis, and excel at improving lipid profiles; FGF-21 analogues are effective at improving steatosis and particularly exhibit strong antifibrotic abilities. GLP-1R agonists showed significant benefits in improving liver steatosis, glucose metabolism, and body weight. GLP-1-based polyagonists have demonstrated the most potential efficacy overall in terms of comprehensive curative effect. Pan-PPAR agonists showed distinct advantages in improving liver function and glucose metabolism. ConclusionThese results illustrate the relative superiority of the five classes of therapy in the treatment of MASLD and may serve as guidance for the development of combination therapies.

Targeting ketone body metabolism to treat fatty liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disorder marked by excessive accumulation of lipids within the liver. If untreated, this condition can progress to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and ultimately, hepatocellular carcinoma (HCC). Given the liver's pivotal role in glucose and fatty acid metabolism, disruptions in these processes are commonly observed in MASLD. Ketone bodies, crucial energy metabolites primarily produced in the liver, are also closely related to the progression of MASLD. Recent studies have demonstrated that disrupted ketogenesis not only accompanies MASLD, but may also play a causal role in its development and progression. Moreover, activation of the ketogenic pathway has been suggested as a promising strategy for reducing excessive hepatic fat accumulation. This review focuses on the regulation of ketogenesis in MASLD, emphasizing the significance of dietary and pharmacological interventions as potential therapeutic approaches to treat fatty liver disease.

Expression of TWEAK/Fn14 axis in the context of metabolic dysfunction associated-fatty liver disease: an approach in liver regeneration

Background: One of the pathways involved in liver regeneration processes is TWEAK/Fn14 (tumor necrosis factor-related weak inducer of apoptosis/fibroblast growth factor-inducible 14), which has been proposed to act directly and selectively on hepatic progenitor cells; however, its role in the regeneration of steatotic liver metabolic dysfunction associated fatty liver disease has not been fully elucidated. Objective: To evaluate the behavior of Fn14 and its ligand TWEAK, as well as cellular stress signals as biochemical cues for possible liver regeneration in MAFLD. Materials and methods: A prospective study was carried out where the behavior of Fn14 and its ligand TWEAK, as well as cellular stress signals were observed as biochemical indications of a possible liver regeneration in a condition of tissue damage caused by excessive lipid accumulation. The expression of TWEAK, Fn14 and heat shock proteins in hepatic steatosis of non-alcoholic origin was assessed using immunohistochemistry and western blotting. Results: The histological classification of the tissues under study corresponded to microvesicular steatosis. We report a high level of expression of heat shock proteins in the cytoplasm. The expression of TWEAK and Fn14 in liver tissue affected by lipid accumulation was localized in the cytoplasm of hepatocytes, showing a higher intensity of reactivity for Fn14 compared to its ligand TWEAK. Conclusion: The expression of TWEAK/Fn14 axis was positive suggesting reactivity of the signaling pathway in metabolic dysfunction associated fatty liver disease.

Benign pericholecystic regeneration mimicking hepatocellular carcinoma: a potential pitfall in imaging of cirrhosis.

Several pseudolesions mimicking malignancy have been reported in cirrhotic and non-cirrhotic livers. Pericholecystic regeneration is among those pseudolesions and can occasionally mimic malignancy. Herein we present a case series comprised of 10 cirrhotic patients (majority due to alcoholic liver disease [ALD] or metabolic dysfunction associated steatotic liver disease [MASLD]) with pericholecystic observations initially categorized as highly suspicious for HCC (LR-4 and LR-5) due to their suspicious enhancement pattern which were later proven to be benign based on biopsy, transplantation or imaging criteria (stability of size and morphology on serial CT or MRI for > 2 years). These observations ranged 2-6.3cm in size, were multiple in most patients and universally resulted in indentations of gallbladder. Arterial phase hyperenhancement and washout, features usually attributed to hepatocellular carcinoma (HCC), were seen in most patients. However, ancillary features of malignancy such as diffusion restriction, increased T2 signal, and hypointensity on hepatobiliary phase MRI were not present. Pericholecystic observations, in particular in the setting of ALD and MASLD, should be carefully assessed and possibility of pseudolesion should be considered especially when the observations are multiple, cause indentation of gallbladder, and lack ancillary features of malignancy.

Glycaemic control metrics and metabolic dysfunction-associated steatotic liver disease in children and adolescents with type 1 diabetes.

The aim was to examine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a risk factor for atherosclerotic cardiovascular disease, and its association with glycaemic control metrics in children and adolescents with type 1 diabetes (T1D). We enrolled 244 children and adolescents with T1D (115 girls, mean age: 16.2 ± 3.2 years). The diagnosis of MASLD was defined by the presence of hepatic steatosis on ultrasonography in combination with at least one of five common cardiometabolic risk factors. Metrics of short-term and long-term glycaemic control, blood pressure, lipids, anthropometric characteristics and three genetic variants strongly related to MASLD susceptibility (rs738409 [patatin-like phospholipase domain-containing 3], rs58542926 [transmembrane 6 superfamily member 2] and rs1260326 [glucokinase regulator]) were assessed. Characteristics of these subjects with and without MASLD were compared using the unpaired Student t test, Mann-Whitney test or χ2 test as appropriate. Logistic regression analyses were performed to determine the main independent predictors of MASLD. The prevalence of MASLD was 27.5% in children and adolescents with T1D. Blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein cholesterol, HbA1c and time above range (TAR) were significantly higher in subjects with MASLD than in those without MASLD. Mean HbA1c values from diabetes onset (adjusted odds ratio [OR]: 1.703, 95% confidence interval [CI]: 1.040-2.787, p = 0.034), TAR (adjusted OR: 1.028, 95% CI: 1.009-1.047, p = 0.006) and plasma LDL cholesterol (adjusted OR: 1.045, 95% CI: 1.013-1.078, p = 0.004) were independently associated with the presence of MASLD. MASLD is a common condition in children and adolescents with T1D. The mean HbA1c values from diabetes onset, TAR and LDL cholesterol levels were the independent predictors of MASLD.

Epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD)

Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) together represent the majority of individuals with steatotic liver disease (SLD). MASLD and ALD prevalence continues to rise globally, which is driven by several factors including an aging population, increasing prevalence of cardiometabolic risk factors such as obesity and diabetes mellitus, and the increasing trends in high-risk unhealthy alcohol use which surged during the COVID-19 pandemic. As a result, MASLD, as well as ALD-related cirrhosis and hepatocellular carcinoma, is also on the rise, becoming major etiologies contributing to end-stage liver disease among adults awaiting liver transplantation. Accurately understanding MASLD and ALD epidemiology is critical to guide healthcare resource planning and health policy. Accurate estimates of MASLD and ALD epidemiology are particularly important to understand in the context of recent updates in nomenclature terminology. This review provides an updated assessment of existing literature describing the epidemiology of MASLD and ALD.

Weight-adjusted waist index is positively and linearly associated with all-cause and cardiovascular mortality in metabolic dysfunction-associated steatotic liver disease: findings from NHANES 1999-2018.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Body mass index (BMI) is the most used obesity index but has important limitations. The weight-adjusted waist index (WWI) is a novel obesity metric and accurately reflects body composition. We explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in MASLD. Adult participants with MASLD were included from NHANES 1999-2018. WWI was calculated by dividing the waist circumference (WC) by the square root of body weight. MASLD was diagnosed by the presence of hepatic steatosis and at least one cardiometabolic risk factor in the absence of other causes of steatosis. A fatty liver index ≥60 suggested the presence of hepatic steatosis. Mortality data was obtained by prospectively linking to the National Death Index. Multivariate Cox proportional hazards regression analyses were used to explore these associations and multiple adjustment models were constructed including crude, partial, and fully adjusted models. After adjusting for all covariates including BMI, WWI remained positively and linearly associated with all-cause and CVD mortality in MASLD (hazard ratios [HR] 1.247 and 1.218, respectively). Higher WWI was associated with a significantly increased risk of mortality (both p for trend <0.05). There was an "obesity paradox" between BMI and all-cause mortality in MASLD, with significantly lower all-cause mortality in those with overweight/obesity compared to normal BMI (HR 0.625 and 0.596, respectively, p for trend = 0.024), and no association between BMI and CVD mortality. Interaction analyses indicated that these associations were influenced by several demographic variables and disease status. Time-dependent receiver operating characteristic curves indicated that the predictive value of WWI for mortality in MASLD was higher than that of BMI, WC, and waist-to-height ratio across all follow-up durations. WWI was positively and linearly associated with all-cause and CVD mortality in MASLD, whereas BMI did not accurately reflect mortality risk. WWI provided the optimal predictive value for mortality compared to traditional obesity indicators. These findings emphasize the potential use of WWI as a novel obesity indicator for mortality risk assessment, stratification, and prevention in MASLD.

Long-term antibody response after the third dose of inactivated SARS-CoV-2 vaccine in MASLD patients

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) patients are at an elevated risk of developing severe coronavirus disease 2019 (COVID-19). The objective of this study was to assess antibody responses and safety profiles six months after the third dose of the inactivated acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in MASLD patients.MethodsThis study included MASLD patients and healthy volunteers without a history of SARS-CoV-2 infection. Blood samples were collected six months after receiving the third dose of the inactivated vaccine to measure the levels of neutralizing antibodies (NAbs) and anti-spike IgG antibodies against SARS-CoV-2.ResultsA total of 335 participants (214 MASLD patients and 121 healthy volunteers) were enrolled. The seroprevalence of NAb was 61.7% (132 of 214) in MASLD patients and 74.4% (90 of 121) in healthy volunteers, which was a significant difference (p = 0.018). Statistically significant differences in IgG seroprevalence were also observed between MASLD patients and healthy volunteers (p = 0.004). Multivariate analysis demonstrated that the severity of MASLD (OR, 2.97; 95% CI, 1.32–6.68; p = 0.009) and age (OR, 1.03; 95% CI, 1.01–1.06; p = 0.004) were independent risk factors for NAb negativity in MASLD patients. Moderate/severe MASLD patients had a lower NAb seroprevalence than mild MASLD patients (45.0% vs. 65.5%, p = 0.016).ConclusionLower antibody responses were observed in MASLD patients six months after their third dose of the inactivated vaccine than in healthy volunteers, providing further assistance in monitoring patients who are more vulnerable to hypo-responsiveness to SARS-CoV-2 vaccines.

Sarcopenia and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review

The primary objective of modern medicine is to extend human life expectancy. Currently, the majority of hospital patients across various clinical settings are elderly or advanced-age individuals, often with multiple comorbidities and age-related alterations in peripheral tissues. One such alteration is sarcopenia, a progressive decline in muscle mass, strength, and function, which significantly increases the risk of disability and mortality in older adults. Sarcopenia is associated with numerous adverse outcomes, and its underlying mechanisms are the subject of ongoing research. This narrative review discusses the epidemiology, pathophysiology, and diagnostic criteria for sarcopenia. It also examines the connections between sarcopenia and metabolic dysfunction-associated steatotic liver disease (MASLD), highlighting potential treatment approaches for the coexistence of these two pathologies.

ADHERENCE TO THE MEDITERRANEAN DIET IN PATIENTS WITH HIGH CARDIOVASCULAR RISK

Introduction. Recommendations for the use of the Mediterranean diet apply to many nosologies, which made it expedient to consider the principles of such nutrition and adherence to it for patients with high cardiovascular risk. Objectives. In order to evaluate the nature of the diet of patients with high cardiovascular risk and their adherence to the Mediterranean diet, the principles of the diet were described according to the data from the Pubmed database. Adherence to and compliance with the principles of Mediterranean diet in patients with high cardiovascular risk were determined according to the Food Questionnaire in 29 outpatients with stable chronic forms of coronary heart disease and arterial hypertension: 18 men, 11 women aged 55.72±2.59 years with excessive body weight; the results were processed by the methods of variational statistics. Results. The Mediterranean diet is recommended for patients with high cardiovascular risk, excess body weight, steatotic liver disease, inflammatory bowel diseases, autoimmune changes in the thyroid gland, dementia, chronic obstructive pulmonary diseases, and oncological processes. It is based on grains, cereals, vegetables and fruits, beans, nuts, and seeds; a small amount of meat, eggs, fish, and poultry; olive oil and moderate daily consumption of cheeses and yogurts. According to the Food Questionnaire, patients with a high cardiovascular risk are not sufficiently aware of the principles of this diet, do not fully follow the recommendations for replacing fats with extra virgin olive oil, do not consume enough fish, vegetables, fruits, nuts, whole grain pasta and hard cereals. In addition, they tend to consume meat, soft cereals, ordinary types of bread and pasta, sweets, carbonated beverages, beer, and spirits in excessive amounts or too often. Conclusions. Insufficient awareness and non-adherence to the Mediterranean diet require the activation of educational work to deepen knowledge about its principles and details.

High Levels of Vitamin C Intake Modify Effects of Phthalates on Metabolic Dysfunction-associated Steatotic Liver Disease: A Nationally Representative Study.

High Levels of Vitamin C Intake Modify Effects of Phthalates on Metabolic Dysfunction-associated Steatotic Liver Disease: A Nationally Representative Study.

Incidence of metabolic dysfunction-associated steatotic liver disease and advanced fibrosis and impact of overweight/obesity in elderly population: a nationwide cohort study.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, coinciding with aging population. However, limited studies have evaluated its incidence and progression to advanced fibrosis in the elderly population. Therefore, our study aimed to investigate the incidence of MASLD and advanced fibrosis in this age group. We included 878 686 individuals aged ≥60years from the Korea National Health Insurance Service-Senior cohort. After excluding participants with preexisting MASLD, 329 388 individuals were finally analyzed. Participants were categorized into four groups based on the presence of overweight/obesity and additional risk factors (aRF) included in the cardiometabolic diagnostic criteria of MASLD. The overall incidence of MASLD was 1.94 per 100 person-years, and the incidence of advanced fibrosis in MASLD patients was 1.78 per 100 person-years. MASLD development was significantly higher in overweight/obese patients (2.65 per 100 person-years) compared to lean patients (1.09 per 100 person-years), and this trend persisted after stratification by the presence of aRF. Similarly, the incidence of advanced fibrosis among MASLD patients was higher in overweight/obese individuals (2.06 per 100 person-years) compared to lean counterparts (0.87 per 100 person-years), irrespective of aRF. The lower incidence of MASLD in the elderly population compared to the general population underscores the importance of identifying age-specific risk factors. Overweight/obesity emerged as a robust predictor of MASLD development and advanced fibrosis. Additionally, the presence of additional cardiometabolic risk factors further increased the risk of incident MASLD and advanced fibrosis among the elderly.

Interplay among IL1R1, gut microbiota, and bile acids in metabolic dysfunction-associated steatotic liver disease: a comprehensive review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by hepatic steatosis associated with metabolic abnormalities. Recent research has shed light on the intricate interplay among interleukin-1 receptor 1 (IL1R1), gut microbiota, and bile acids in the pathogenesis of MASLD. This review aims to provide a comprehensive overview of the current understanding of the role of IL1R1, gut microbiota, and bile acids in MASLD, exploring their interrelationships and potential mechanisms. We summarize the evidence supporting the involvement of IL1R1 in inflammation, discuss the influence of gut microbiota on bile acid metabolism and its influence on liver health, and elucidate the bidirectional interactions among IL1R1 signaling, gut microbiota composition, and bile acid homeostasis in MASLD. Furthermore, we highlight emerging therapeutic strategies targeting these interrelated pathways for the management of MASLD.

Analysis of the Association between Eosinophilic Esophagitis and MASLD: Retrospective, Observational, Cohort Analysis of the National Inpatient Sample 2016-2020.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory condition. Associated pathologies for EoE are similar to those with metabolic-dysfunction-associated steatotic liver disease (MASLD). This study assesses whether an association exists between MASLD and EoE. We used National Inpatient Sample (NIS) 2020 data to identify adult patients. ICD-10 codes were used to identify patients with MASLD and EoE. The relationship between MASLD and EoE was assessed by multivariate analysis after adjusting for confounding factors, such as patient demographics, hospital characteristics, Charlson comorbidity index, obesity, obstructive sleep apnea (OSA), diabetes, hypertension (HTN), hyperlipidemia (HLD), inflammatory bowel disease (IBD), celiac disease (CD), gastroesophageal reflux disease (GERD), smoking, alcohol use, and irritable bowel syndrome (IBS). Out of 26 million patients, 4,820 had a diagnosis of EoE. The majority of the patients were between 18 and 44 years of age (47.82%), male (54.05%), had private insurance (50.1%), and were in the highest income quartile (29.25%). A higher incidence of MASLD was noted in the EoE group than those without (6.1% vs.2.9%, p<0.001). After adjusting for confounding factors, MASLD had 2.38 times higher odds of having EoE (95% CI-1.82-3.11, p<0.001). Other factors noted to be associated with higher odds of EoE included younger age, Caucasian race, IBS, GERD, IBD, and CD. Our study reports a novel finding that MASLD and EoE are associated. Future prospective studies are needed to confirm and understand the clinical significance of this relationship and how one disease affects the other.

A weekly 4-methylpyrazole treatment attenuates the development of non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in male mice: Role of JNK.

4-methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism of ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess a potential in the treatment of intoxication from other substance, for example, acetaminophen, and to modulate JNK-dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet-induced non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in C57BL/6 mice. Male C57BL/6 mice (6-8 weeks old, n = 7-8/group) were pair-fed either a liquid control diet (C) or a liquid sucrose-, fat- and cholesterol-rich diet (SFC) for 8 weeks while being concomitantly treated with 4MP (50 mg/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin-challenged J774A.1 cells pretreated with 4MP, pro-inflammatory markers were assessed. The concomitant treatment of SFC-fed mice with 4MP attenuated the increase in JNK phosphorylation and pro-inflammatory markers like IFNγ, IL-6 and 3-nitrotyrosine protein adducts in liver tissue found in vehicle-treated SFC-fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin-stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro-inflammatory mediators like IL-6 and Mcp1. Taken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non-obese MASLD in mice.

Metabolic dysfunction-associated steatotic liver disease and gallbladder polyp development: an observational study

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.