Steatotic Livers Research Articles

The multifaceted roles of B lymphocytes in metabolic dysfunction-associated steatotic liver disease.

Recent evidence suggests that adaptive immune cells are important contributors to metabolic dysfunction-associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease, NAFLD). In liver biopsies from MASLD patients, the accumulation of intrahepatic B cells is positively correlated with the MASLD activity score. Hepatic B-cell infiltration is observed in experimental models of metabolic dysfunction-associated steatohepatitis (MASH, formerly non-alcoholic steatohepatitis, NASH). Intrahepatic B2 cells have been shown to contribute to MASLD/MASH by activating T cells, macrophages and hepatic stellate cells, and by producing pathogenic IgG antibodies. In mice fed a MASH diet, selective depletion of B2 cells reduces steatohepatitis and fibrosis. Intestinal B cells are metabolically activated in MASH and promote T-cell activation independently of TCR signaling. In addition, B cells have been shown to contribute to liver fibrosis by activating monocyte-derived macrophages through the secretion of IgA immunoglobulins. Furthermore, our recent study indicates that certain B cell subsets, very likely regulatory B cells, may play a protective role in MASLD. This review summarizes the molecular mechanisms of B cell functions and discusses future research directions on the different roles of B cells in MASLD and MASH.

Sex-specific associations of metabolic dysfunction-associated steatotic liver disease with cardiovascular outcomes

Sex-specific associations of metabolic dysfunction-associated steatotic liver disease with cardiovascular outcomes

Intestinal microbiota and metabolically associated steatotic liver disease: current understanding of the problem. Review

Cross‑interaction of microbes, microbial products, and the intestinal barrier are components of the so‑called «intestine‑liver axis», as the liver and intestines have a close two‑way relationship. In patients with metabolically associated steatotic liver disease (MASLD), significant characteristic changes in the intestinal microbiome are observed, in particular, the growth of gram‑negative bacteria, which contributes to the formation of a pro‑inflammatory status (primarily due to endotocins) and disruption of metabolic processes, while an increase in Bacteroides and Ruminococcus and a decrease in Prevotella are associated with severe stages of liver fibrosis. Intestinal microbiota modulates the pool of bile acids thereby affecting metabolic homeostasis and pro‑inflammatory processes. Dysbiosis associated with MASLD is characterized by an excess of bacteria — producers of secondary bile acids, which are one of the factors in the progression of metabolically associated steatohepatitis. In addition, dysbiosis leads to increased production of short‑chain fatty acids, which promotes gluconeogenesis, synthesis and accumulation of toxic lipids in the liver and, accordingly, the development and progression of MASLD. But liver function disorders connected with dysbiosis are associated not only with intestinal bacteria, but also with fungi and viruses. According to the results of recent studies, MASLD is associated with a significant diversity of the mycobiome and has certain differences in the progression of the disease depending on the degree of liver inflammation and the stage of fibrosis. Chronic hyperproduction of endogenous ethanol (Klebsiella pneumoniae, Escherichia, Candida, etc.) is an important factor in the pathogenesis of MASLD, as it disrupts glucose and lipid metabolism, contributing to the formation of liver steatosis and steatohepatitis. Ultrastructural and functional changes of mitochondria are recognized determinants in the pathogenesis of MASLD. Mitochondria and intestinal microbiota have a bidirectional relationship: microbiota supplies metabolites for mitochondrial metabolism and redox homeostasis, and the development of dysbiosis contributes to oxidative stress and proinflammatory status — key factors in the development of metabolically associated steatohepatitis. Mitochondria can also modulate intestinal microflora by affecting the permeability of the intestinal barrier. The data presented in the article expand our knowledge about the interaction of the liver and the intestine and inspire the development of new promising therapeutic approaches to the treatment of MASLD, which involve a synergistic effect on the intestinal microbiota, microbiome, virome, and mitochondrial function.

Global Epidemiology of Cirrhosis in Women

Recent epidemiological evidence indicates a significant rise in cirrhosis burden over the past two decades in all parts of the world, with cirrhosis incidence rates and related deaths escalating quickly. Women face unique risk factors and susceptibility to chronic liver diseases compared to men, underscoring the need for a sex-specific approach in early identification, reversal of causative factors, and complications prevention. This review aims to explore epidemiological trends and sex-specific factors contributing to the global epidemiology of cirrhosis among females today. While cirrhosis prevalence remains higher in males globally, the incidence rate from 2010 to 2019 grew faster among females. The female-to-male incidence ratio of metabolic-associated steatotic liver disease (MASLD) related cirrhosis globally in 2019 was 1.3, indicating a shifting trend towards new diagnoses among women now surpassing that of men. Alcohol-associated cirrhosis (AC) epidemiology is also changing, with trends towards equal incidence of AC between both sexes, particularly in industrialized nations with increased alcohol accessibility. Cirrhosis from viral hepatitis remains the main etiology among females in endemic regions. Sex differences in epidemiology are likely multifactorial, influenced by varying risk factors, susceptibility and behaviors between sexes. Further research is necessary to better understand these disparities and to tailor sex-specific interventions towards improved management and treatment strategies, ultimately enhancing outcomes for women with cirrhosis and providing better patient-centered care.

Efficacy and Safety of FGF21 Versus Semaglutide in the Management of Metabolic-Associated Steatotic Liver Disease: A Network Meta-analysis

Efficacy and Safety of FGF21 Versus Semaglutide in the Management of Metabolic-Associated Steatotic Liver Disease: A Network Meta-analysis

Prevalence and risk factors of significant fibrosis in chronic hepatitis B patients with concurrent metabolic dysfunction-associated steatotic liver disease

Introduction and objectivesSignificant fibrosis is an indicator of clinical intervention for both chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD). There remains a paucity of data regarding the clinical impact of biopsy-defined MASLD on significant fibrosis in CHB patients. The current study aims to elucidate whether patients with concomitant MASLD are at higher risk of significant fibrosis in patients with CHB. Patients and methodsThis retrospective research of two tertiary hospitals comprised 1818 patients between 2009 and 2021 with CHB and hepatic steatosis who had not received antiviral therapy. Pathologic findings by liver biopsy were contrasted between CHB group (n = 844) and CHB + MASLD (n = 974) group. METAVIR values of F≥2 were used to categorize significant fibrosis. ResultsPatients with CHB + MASLD had more significant fibrosis (35.5 % vs. 23.5 %, p < 0.001) than CHB group. The presence of MASLD [adjusted odds ratio (aOR) 2.055, 95 % confidence interval (CI) 1.635–2.584; p < 0.001] was strongly associated with significant fibrosis in all CHB patients. There was a trend for patients with more cardiometabolic risk factors (CMRFs) to have a higher prevalence of significant fibrosis: (25.7 % in CMRF1 subgroup v.s. 34.9 % in CMRF2 subgroup v.s. 53.7 % in CMRF≥ 3 subgroup, p < 0.001). Patients with CMRF≥3 had a three-fold higher significant fibrosis than those with just one CMRF. ConclusionsMASLD was associated with higher fibrosis stage in patients with CHB. Early detection and intervention are crucial to patients with three or more cardiometabolic risk factors.

The effect of stress on liver function

«Psychosocial stress» is becoming an increasingly common concept in today’s complex and highly demanding society. Although the liver is one of the body’s most resilient organs, it is still vulnerable to the damaging effects of stress and aging, leading to liver disease, severe scarring and impaired function. Mental stress increases mortality from liver disease. Stressors activate macrophages and trigger an innate immune response, which then leads to the induction of inflammation and liver damage. In its diseases, symptoms such as low energy, fatigue, changes in employment status and functionality can also lead to the development of depression. The various physiological effects of glucocorticoids and catecholamines released into the bloodstream during stress lead to inflammation and oxidative stress in the liver. Research has explained the complex interactions that occur between stress system effectors and inflammation. Chronic psychological stress leads to an increase in serum glucocorticoid concentrations and the release of catecholamines, which increases the need for insulin. Insulin resistance leads to the development of metabolic-associated steatotic liver disease. The high prevalence of hepatogenic fatigue in chronic diffuse liver disease, its negative impact on the quality of life of patients, and the lack of effect of basic treatment lead to its aggravation due to stress. Sublingual S-adenosyl-L-methionine is effective in the treatment of hepatogenic stress fatigue, both in short-term and long-term use as part of the complex therapy of liver diseases.

Indicators of functional state of liver, blood lipid spectrum in patients with steatotic liver disease associated with metabolic dysfunction: modern approaches to complex treatment. Review

Objective — to study the dynamics of indicators of the functional state of the liver, the lipid spectrum of the blood, to evaluate the cardiovascular risk according to SCORE‑2 (Systematic Coronary Risk Estimation 2) scale under the influence of complex pathogenetic treatment of the detected disorders in patients with steatotic liver disease associated with metabolic dysfunction (SLDMD) in combination with obesity. Materials and methods. 46 outpatients with a diagnosis SLDMD were examined: 29 (63.1%) men and 17 (36.9%) women aged 32—55 years. The patients were divided into two groups. The main group included 19 (41.3%) persons who received atorvastatin: 20 mg/day for 90 days. The comparison group consisted of 27 (58.7%) patients who were prescribed ursodeoxycholic acid preparations in combination with atorvastatin: 250 mg (15 mg/kg of body weight) for 90 days. The control group consisted of 12 healthy persons of the appropriate age. The anthropometric criterion of obesity was the Quetelet index. Phenotypic variant of obesity was determined by the ratio of waist circumference/hip circumference (WC/HC). Among the patients of the main group, there were 9 (47.4%) persons with I degree of obesity ((32.6±2.2) kg/m2), 6 (31.5%) persons with II degree ( 35.8±3.6 kg/m2), and 4 (21.1%) persons with III degree (40.0±2.1kg/m2), in the comparison group there were 17 (62.9%), 6 (22.3%) and 4 (14.8%) patients, respectively. All patients received a differentiated diet with the calculation of the energy value, the quota of protein (1.4—1.6 g), fat (1.2—1.4 g), carbohydrates (2—3 g) per 1 kg of ideal body weight and dosed physical activity. For assessing the indicators of the functional state of the disease we determined: the level of general bilirubin and its fractions (direct and indirect), activity of serum aminotransferases, alkaline phosphatase, total cholesterol content in the blood serum, high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol, very‑low‑density lipoprotein cholesterol, triglycerides. Results. In the majority of patients with SLDMD, a statistically significant (p &lt;0.05) increase in the level of direct bilirubin in the blood, the activity of hepatic transaminases, alkaline phosphatase, and changes in the lipid spectrum of the blood were detected. According to the body mass index (BMI) most of the examined patients had visceral obesity. After the course of the combined therapy positive dynamics was marked in biochemical indices of the blood (p &lt;0.05): decrease of the direct bilirubin level, hepatic transaminases, blood phosphatase. The lipid spectrum of the blood was close to normal (p &lt;0.05). The addition of ursodeoxycholic acid to statin therapy contributes to a statistically significant reduction in total cardiovascular risk according to the SCORE 2 scale compared with atorvastatin monotherapy. All patients were recommended to continue the course of treatment (combination of atorvastatin and ursodeoxycholic acid) for 2 to 3 months. Conclusions. The use of a combination of statin and ursodeoxycholic acid in the treatment of patients with SLDMD and obesity helps to normalise the functional state of the liver and blood lipid parameters, reduce the degree of overall cardiovascular risk, and achieve clinical and biochemical remission of the pathological process in the liver.

Gut Microbiota Dysbiosis in the Pathogenesis of Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD)

: Metabolic-dysfunction-associated steatotic liver disease (MASLD), previously referred to as nonalcoholic fatty liver disease (NAFLD), affecting approximately 30% of the global population. Projections suggest that MASLD incidence may rise by up to 56% over the next decade. MASLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in the USA, France, UK, and other regions worldwide. The prevalence of MASLD and MASLD-related liver damage is expected to parallel the increasing rates of obesity and type 2 Diabetes Mellitus (T2DM) globally. The factors contributing to MASLD development and its progression to metabolic-dysfunction- associated steatohepatitis (MASH), fibrosis, cirrhosis, and HCC remain poorly understood. Evidence from cell-based, animal-based, and human-subject studies suggests that insulin resistance, endoplasmic reticulum stress, oxidative stress, impaired autophagy, genetics, epigenetics, reduced immune surveillance, increased gut inflammation, and gut dysbiosis are crucial events in MASLD pathogenesis. In recent years, dysregulation of gut microbiota has emerged as a potential mechanism implicated in MASLD and MASLD-related hepatocarcinogenesis. This review briefly outlines the mechanistic events significant for MASLD pathogenesis. Additionally, it offers insight into dysregulated gut microbiota and its correlation with MASLD and MASLD-related liver damage. Furthermore, it highlights pertinent questions for cell and microbiologists in the MASLD research field. It underscores the necessity for identifying factors leading to gut microbiome dysregulation in MASLD and MASH pathogenesis. Identifying these factors could aid in the development of novel strategies for managing MASLD and MASLD-related liver damage.

Epidemiological and transcriptome data identify association between iron overload and metabolic dysfunction-associated steatotic liver disease and hepatic fibrosis

The primary objective of this study was to examine the association between iron overload (IO), metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatic fibrosis. We hypothesized that there is a significant association. Data from the NHANES (2017-2020) were analyzed to explore IO's impact on MASLD and hepatic fibrosis in U.S. adults. We assessed serum ferritin, controlled attenuation parameter (CAP), liver stiffness measurement (LSM), and various covariates. Gene expression data were sourced from the FerrDb V2 and GEO databases. Differential gene expression analysis, Protein-Protein Interaction (PPI) Network construction, and Gene Ontology (GO) and KEGG pathway enrichment analyses were performed. The study verified the link between MASLD, hepatic fibrosis, and iron overload hub genes. This study of 5927 participants, averaging 46.78 years of age, revealed significant correlations between serum ferritin and CAP, LSM, after adjusting for covariates. Threshold effect analysis indicated nonlinear associations between serum ferritin and CAP, LSM, with distinct patterns observed by age and gender. Moreover, the area under the ROC curve for serum ferritin with MASLD and hepatic fibrosis was 0.8272 and 0.8376, respectively, demonstrating its performance in assessing these conditions. Additionally, molecular analyses identified potential hub genes associated with iron overload and MASLD, and hepatic fibrosis, revealing the underlying mechanisms. Our study findings reveal an association between iron overload, MASLD, and hepatic fibrosis. Additionally, the hub genes may be implicated in iron overload and subsequently contribute to the progression of MASLD and hepatic fibrosis. These findings support precision nutrition strategies.

Ultrasound evaluation of chronic liver disease.

Chronic liver disease is a world-wide epidemic. Any etiology that causes inflammation in the liver will lead to chronic liver disease. Presently, the most common inciting factor worldwide is steatotic liver disease. Recent advances in ultrasound imaging provide a multiparametric ultrasound methodology of diagnosing, staging, and monitoring treatment of chronic liver disease. Elastography has become a standard of care technique for the evaluation of liver fibrosis. Quantitative ultrasound allows for determination of the degree of fatty infiltration of the liver. Portal hypertension is the most important factor in determination of liver decompensation. B-mode findings combined with Doppler, and elastography techniques provide qualitative and quantitative methods of determining clinically significant portal hypertension. A newer method using contrast enhanced ultrasound may allow for a non-invasive quantitative estimation of the portal pressures. This paper reviews the use of multiparametric ultrasound in the evaluation of chronic liver disease including conventional B-mode ultrasound, Doppler, elastography and quantitative ultrasound for estimation of liver fat. The recent guidelines are presented and advised protocols reviewed.

Novel eicosanoid signature in plasma provides diagnostic for metabolic dysfunction-associated steatotic liver disease

There is a clinical need for a simple test implementable at the primary point of care to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) in the population. Blood plasma samples from adult patients with varying phenotypes of MASLD were used to identify a minimal set of lipid analytes reflective of underlying histologically confirmed MASLD. Samples were obtained from the NIDDK Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database prospective cohort study (MASLD group; N = 301). Samples of control subjects were obtained from cohort studies at the University of California San Diego (control group; N = 48). Plasma samples were utilized for targeted quantitation of circulating eicosanoids, related bioactive metabolites, and polyunsaturated fatty acids by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) lipidomics analysis. Bioinformatic approaches were used to discover a panel of bioactive lipids that can be used as a diagnostic tool to identify MASLD. The final panel of fifteen lipid metabolites consists of 12 eicosanoid metabolites and 3 free fatty acids that were identified to be predictive for MASLD by multivariate area under the receiver operating characteristics curve (AUROC) analysis. The panel was highly predictive for MASLD with an AUROC of 0.999 (95% CI = 0.986–1.0) with only one control misclassified. A validation study confirmed the resulting MASLD LIPIDOMICS SCORE, which may require a larger-scale prospective study to optimize. This predictive model should guide the development of a non-invasive “point-of-care” test to identify MASLD patients requiring further evaluation for the presence of metabolic dysfunction-associated steatohepatitis.

Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children. Liver biopsy is considered the gold standard for diagnosis. Magnetic resonance elastography (MRE) and transient elastography (TE) are imaging modalities that can monitor fibrosis and steatosis noninvasively. More studies are needed to identify whether imaging modalities can provide accurate and reproducible data. We hypothesize that MRE provides reliable data similar to that of TE when compared to liver biopsy in children with MASLD/metabolic dysfunction-associated steatohepatitis. We conducted a retrospective chart review of children with liver biopsy-proven MASLD at Children's Hospital Los Angeles between September 2017 and January 2023, investigating and comparing the predictive accuracy of MRE and TE in the detection of high-grade fibrosis on liver biopsy. Seventy-seven patients were reviewed, all of whom had undergone liver biopsy, MRE and TE for evaluation of MASLD. Fibrosis was identified in 90% of liver biopsies. The area under the receiver operating characteristic curves (AUROC) of MRE and TE for detection of high-grade fibrosis were 0.817 and 0.750, respectively, and not significantly different (p = 0.4785). We demonstrate that MRE and TE did not accurately predict high-grade fibrosis on liver biopsy. Between the two noninvasive imaging modalities, the correlation of identifying high-grade fibrosis was not statistically different; however, the AUROC for MRE was slightly superior to that of TE. Studies with larger cohorts will be required to validate these findings.

Comparable glucagon-stimulated amino acid suppression in individuals with and without hepatic steatosis or steatohepatitis.

Hepatic amino acid (AA) metabolism and glucagon secretion are linked in a feedback cycle in which circulating AAs stimulate glucagon secretion, while glucagon stimulates hepatic AA catabolism. It has been proposed that metabolic dysfunction-associated steatotic liver disease (MASLD) leads to hepatic glucagon resistance, which may result in hyperaminoacidemia and hyperglucagonemia. We tested the glucagon effect on AA metabolism in subjects with obesity; 11 with steatohepatitis (MASH), 10 with steatosis (MAS), and seven subjects (CON) without steatosis. We performed a somatostatin clamp with infusions of insulin and low-dose followed by high-dose glucagon. We measured plasma levels of 17 AAs and assessed hepatic fat content (FF%) and body fat distribution (visceral and subcutaneous adipose tissue mass) by MRI. HighGlucagon suppressed plasma total AA equally in all groups; MASH 13% (SD 9%), MAS 14% (7%), CON 11% (5%), respectively. In univariate regression analyses visceral adipose tissue mass (β = 0.471, P = 0.011) and AA concentration at LowGlucagon (β = ─0.524, P = 0.004), but not FF% (β = ─0.243, P = 0.213), were significant predictors of AA reduction. Using a stepwise backward multiple regression approach revealed similar results. Total and specific AA levels (glutamic acid, tyrosine) were higher in both MASLD groups during the study and FF% was positively correlated to a number of individual AAs. Though finding elevated AA concentrations in subjects with MASLD, we conclude that in MASLD patients that do not have elevated glucagon at baseline, glucagon suppresses circulating AA levels equally in subjects with and without MASLD. NCT04042142.

Prevalence of subclinical hypothyroidism and longitudinal thyroid stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: an observational study.

Studies on adults have shown an association between overt or subclinical hypothyroidism (SH) and metabolic dysfunction-associated steatotic liver disease (MASLD). The goal of this study was to assess the relationship between thyroid-stimulating hormone (TSH) levels and the histological characteristics of MASLD in youth. This observational study used prospectively collected liver biopsy and clinical data from youth enrolled in two pediatric clinical trials in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Thyroid assays were compared between youth with MASLD and population-based controls aged ≤18 years from the National Health and Nutrition Examination Survey (NHANES). Individuals with overt hypothyroidism, abnormal anti-thyroid antibody, or thyroid-related medications were excluded. SH was defined as TSH between 4.5-10.0uIU/L. Multinomial logistic regression was used to test the association between TSH and MASLD histological changes at baseline, adjusting for age, sex, race/ethnicity, and body mass index. Mixed-effect models, including treatment and time, were used for the longitudinal analysis. Mean TSH, total thyroxine (T4), total triiodothyronine (T3), and free T4 levels were higher (p<0.001) in the NASH CRN cohort (n=218; 421 observations) than in the NHANES cohort (n=2,198). TSH levels were positively associated with increased steatosis over time (p=0.03). SH was associated with borderline or definite metabolic-associated steatohepatitis on histology at baseline (p=0.03) and with changes in fibrosis over time (p=0.01). The association between TSH and steatosis severity in individuals with normal thyroid hormone concentrations suggests an independent role of TSH in MASLD.

Extracellular Matrix and Hepatic Wound Healing before Fibrosis.

The hepatic extracellular matrix (ECM) is most accurately depicted as a dynamic compartment that comprises a diverse range of players that work bidirectionally with hepatic cells to regulate overall homeostasis. Although the classic meaning of the ECM referred to only proteins directly involved in generating the ECM structure, such as collagens, proteoglycans, and glycoproteins, the definition of the ECM is now broader and includes all components associated with this compartment. The ECM is critical in mediating phenotype at the cellular, organ, and even organismal levels. The purpose of this review is to summarize the prevailing mechanisms by which ECM mediates hepatic phenotype and discuss the potential or established role of this compartment in the response to hepatic injury in the context of steatotic liver disease.

The phenotype of the pediatric patient with Cushing syndrome but without obesity.

Cushing syndrome (CS) often presents with obesity that is not as severe in children as it is in adults. The role of obesity in the severity of metabolic syndrome in children with CS has not been studied. This study evaluates whether pediatric patients with CS have obesity-specific differences in their demographic, biochemical, and presenting findings. Cohort study. We analyzed 273 patients with young onset of CS at ≤18 years old and who were classified as patients with or without obesity based on their BMI z scores. Patients without obesity (n = 84, 31%) were more frequently females with an older age of onset compared with patients with obesity (n = 189, 69%). Consistent with their older age, patients without obesity were also more likely to have advanced Tanner stages. Patients with and without obesity had a similar duration of disease, but patients with obesity showed higher markers of hypercortisolemia (urinary free cortisol, UFC). A higher prevalence of hypertension and insulin resistance was seen in patients with obesity than those without obesity, adjusting for UFC (P < .05 for all comparisons). While fatty liver disease was not statistically different among the entire cohort, elevated alanine transaminase and metabolic dysfunction-associated steatotic liver disease scores were more common in ACTH-dependent CS patients with obesity (P < .05). Weight gain appears to mediate some but not all the cortisol-associated complications in pediatric CS. Therefore, obesity may be a modifiable risk factor among these patients.

Clinical-Biological Particularities and Clinical Forms of Metabolic Liver Steatosis in a Group of Romanian Patients

Formerly named Non-alcoholic fatty liver disease (NAFLD) is now known as Metabolic associated steatotic liver disease (MASLD) and is frequent pathology in daily clinical practice. The paper present a study of 125 romanian patients with MASLD with anlysis of important data on the characteristics of disease in our geographical area, with highlight on some interesting correlations between clinical and biological features and the particularities of the disease: correlations between clinical aspects and laboratory examinations (imaging, biochemical), frequency and type of risk factors, clinical aspects and forms of liver steatosis, associated diseases, biochemical characteristics.

Associations of Cannabis Use, Metabolic Dysfunction-Associated Steatotic Liver Disease, and Liver Fibrosis in U.S. Adults.

Introduction: Following the introduction of metabolic dysfunction-associated steatotic liver disease (MASLD) as a replacement term for nonalcoholic fatty liver disease, the relationship between MASLD and cannabis use has yet to be established. With the global rise in cannabis consumption, understanding its impact on MASLD is critical for clinical guidance. Our study investigated the association between cannabis use, MASLD, and clinically significant fibrosis (CSF) among U.S. adults. Methods: Data were collected from the National Health and Nutrition Examination Survey for the period 2017 to 2018 to conduct a cross-sectional analysis. The diagnosis of hepatic steatosis and CSF was based on median values of the controlled attenuation parameter and liver stiffness measurement, with thresholds of 285 dB/m and 8.6 kPa, respectively. Information on cannabis use was obtained through self-report questionnaires. Multinomial logistic regression models and subgroup analyses were used to investigate the association between cannabis use and MASLD with CSF. Results: Our study assessed data from 2,756 U.S. adults (51.1% female; 32.2% white; mean age 39.41 ± 11.83 years), who had complete information on liver stiffness measurements through transient elastography alongside reported cannabis use. Results indicated that cannabis use overall was not associated with liver stiffness in patients with MASLD. However, among females, cannabis use was associated with MASLD accompanied by CSF, with an adjusted odds ratio (OR) of 0.47 (95% confidence interval [CI]: 0.24-0.91). Heavy cannabis use (9 to 30 times per month) was associated with MASLD accompanied by CSF among female participants, with an adjusted OR of 0.12 (95% CI: 0.02-0.88). Conclusion: In our study, cannabis use did not show a significant association with liver stiffness in patients diagnosed with MASLD. However, heavy cannabis consumption in women was associated with MASLD accompanied by CSF. These findings suggest that the effects of cannabis on liver health may differ based on gender and frequency of cannabis use, emphasizing the need for further research in this area.

Glycogenic hepatopathy associated with hepatic steatosis in type 1 diabetes

AimsGlycogenic hepatopathy is associated with significant psychosocial consequences and health costs. Metabolic Dysfunction-Associated Steatotic Liver Disease and glycogenic hepatopathy are frequently confused as “fatty liver” when seen on ultrasonography. We wished to examine liver fat and glycogen content in groups defined based on metabolic and liver disease phenotypes. MethodsThis case-control study undertaken in a tertiary hospital used nuclear proton magnetic resonance spectroscopy (1H-MRS) to examine liver fat and glycogen content in five clinical groups, each containing five participants: 1. type 1 diabetes with glycogenic hepatopathy, 2. satisfactorily controlled type 1 diabetes with no liver disease, 3. poorly controlled type 1 diabetes without liver disease, 4. a control group of body mass index- and age-matched individuals without diabetes or liver disease, and 5. hepatic steatosis. ResultsFat content was highest in the hepatic steatosis (median 15.4 %, IQR 10.0–19.3) and glycogenic hepatopathy (median 6.5 %, IQR 4.5–9.1) groups and compared to both of these groups was lower in the control group (median 1.0 %, IQR 0.7–1.1, p 0.002 and 0.022), the T1DM group with satisfactory control (median 0.3 %, IQR 0.2–0.6, p < 0.001 and <0.001), and the T1DM group with poor control without liver disease (median 1.1 %, IQR 0.9–1.1, p 0.001 and 0.012).No participants from the type 1 diabetes poor control, type 1 diabetes satisfactory control or the no diabetes groups had 1H-MRS-diagnosed hepatic steatosis.1H-MRS glycogen content could not be interpreted in the majority of those with glycogenic hepatopathy because of interference from the fat signal. ConclusionsIn cases diagnosed with glycogenic hepatopathy there may be significant concomitant fat accumulation, compounding the already elevated cardiovascular risk in this cohort.The technique of 1H-MRS has not been demonstrated to be useful for diagnosing glycogenic hepatopathy.