Steatosis Levels Research Articles

Elevated non-HDL-C to HDL-C ratio as a marker for NAFLD and liver fibrosis risk: a cross-sectional analysis.

Dyslipidemia is a known independent risk factor for Nonalcoholic fatty liver disease (NAFLD). However, the relationship between NAFLD and the serum non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio remains unclear. This study examined the association between the non-HDL-C to HDL-C ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population. We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4798 participants. Liver ultrasound and Transient Elastography (TE) were used to assess fibrosis and steatosis. Adjusted multivariable regression analyses, subgroup analyses based on BMI and sex, and a generalized additive model were employed to investigate the relationship between the non-HDL-C/HDL-C ratio and NAFLD. Among the 4798 participants, 39.27% (n = 1,884) had NAFLD. Significant positive correlations between non-HDL-C/HDL-C and NAFLD risk were found across all models, with sex-stratified analyses indicating higher risk in men. Liver fibrosis was also associated with non-HDL-C/HDL-C ratios. The Receiver operating characteristic (ROC) analysis shows non-HDL-C/HDL-C as a better predictor for NAFLD than non-HDL-C or HDL-C alone. Elevated non-HDL-C/HDL-C levels are independently associated with increased NAFLD and liver fibrosis risk in the American population, suggesting its utility in predicting NAFLD and related liver fibrosis.

Relationship between Parathyroid Hormone Level and Degree of Hepatic Steatosis by Fibroscan among Prevalent Hemodialysis Patients

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MS) which may be related to cardiovascular mortality among hemodialysis (HD) patients. Hepatic steatosis contributed to many factors related to MS, atherogenic dyslipidemia, insulinresistance, and adipose tissue hormones. Elevated parathyroid hormone is associated with insulin resistance and atherosclerosis and may be considered an independent predictor of metabolic syndrome. some studies reported an association between elevated PTH and non-alcoholic steatohepatitis. However, the relationship between hyperparathyroidism and NAFLD in HD patients is not well defined. Aims of the Study To test the hypothesis of a possible association between hyperparathyroidism and the presence of hepatic steatosis and fibrosis by transient elastography and to evaluate the possible risk factors of NAFLD among hemodialysis patients. Patients and Methods This is a Case-control study included: Group I: (30) chronic HD patients with NAFLD, Group II: (25) chronic HD patients without NAFLD, and Group III: 30 healthy volunteers as a control group. Infection with a hepatotropic virus, Diabetes mellitus (DM), patients with a history of recent hepatobiliary surgery, Abdominal Ascites, Active infection, fever, Active malignancy, drugs induce hepatic steatosis, or Alcohol abuse were excluded. All subjects were subjected to full history and clinical examination. Laboratory tests: Complete blood count (CBC), Iron profile, Serum creatinine, Urea, Calcium (Ca), phosphorus, Intact parathyroid hormone (iPTH), Serum Alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), Serum Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Albumin, Total bilirubin, Total cholesterol, High-density lipoprotein cholesterol (HDL), Low-density Lipoprotein cholesterol (LDL), Triglycerides (TG), C -reactive protein (CRP) Titre, HBsAg, HCV Ab and Urea reduction ratio (URR). Transient elastography Fibroscan® for assessment of Controlled attenuation parameter (CAP) to detect liver steatosis grades and liver stiffness measurement to quantitate liver fibrosis was done. Results The mean ±SD values of CAP of liver steatosis (263.7 ± 52.7, 181.3 ± 23, 210.8 ± 33.7) (dB/m) in group I, II and control group respectively (P < 0.001). There were significant differences between the studied group as regard body mass index (BMI), serum Ca, phosphorus, ALP and GGT and CRP titer, PTH and liver function tests, and lipid profile (P < 0.001). Post Hoc analysis revealed a significant statistical difference between group I and II groups as regard ALT, AST, Bilirubin level and serum albumin, CRP titer, and lipid profile (P < 0.5). In HD patients studied groups, the CAP value of liver steatosis was statistically significantly correlated to BMI ALT (r = 0.387, P=0.004), AST (r = 0.365, P = 0.006), Cholesterol (r = 0.785, P < 0.001), LDL (r = 0.692, P < 0.001), TG (r = 0.668, P <0.001), CRP Titre (r=0.384, P=0.004), but not correlated to PTH or other studied parameters (P > 0.05). In control group III, there was a significant correlation between the measured CAP Value of liver steatosis and BMI, PTH, CRP titer, ALT, AST, cholesterol, LDL, and a negative correlation between HDL and CAP value (P < 0.05). liver stiffness /fibrosis was observed in 18 (60.0%) of HD patients in group I versus 8 (32%) patients in group II (P < 0.05). The mean value of liver stiffness (Kpa) was (6.73 ± 6.08, 6.39 ± 5.65, 4.57 ± 0.75) in groups I, II, and the control group respectively (P < 0.001) and post hoc analysis showed a significant difference between Group I and Group II (P = 0.04) and between group I and control group p (<0.001). There was a significant difference between group I and group II and between group I and the control group regarding mean values of liver stiffness (Kpa) (P < 0.05) Conclusions Non-alcoholic liver disease (NAFLD) in prevalent hemodialysis patients is significantly correlated to high cholesterol, LDL, triglycerides, low HDL, increased body mass index, and CRP titer as a marker of inflammation, but not significantly correlated to elevated parathyroid hormone level. NAFLD is a risk for liver stiffness /fibrosis among chronic hemodialysis patients.

Gut microbiota of miR-30a-5p-deleted mice aggravate high-fat diet-induced hepatic steatosis by regulating arachidonic acid metabolic pathway.

Patients with non-alcoholic fatty liver disease (NAFLD) often exhibit hepatic steatosis and dyslipidemia. Studies have shown that intestinal microorganisms are closely related to the occurrence of NAFLD and atherosclerosis. Our previous study has underscored the protective role of microRNA-30a-5p (miR-30a-5p) against atherosclerosis. In the present study, we aimed to elucidate the effect and underlying mechanism of the intestinal microorganisms of miR-30a-5p knockout (KO) mice on NAFLD. Our findings demonstrated that KO exacerbated high-fat diet (HFD)-induced hepatic steatosis and disrupted liver function, as evidenced by elevated levels of total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, and total bile acids in serum. Fecal microbiota from HFD-fed KO mice induced hepatic steatosis, dyslipidemia, and higher levels of enzymes indicative of liver damage in wild-type mice. Remarkably, KO mice significantly intensified the above effects. 16s rDNA sequencing and metabolomics of the intestinal microbiota in the HFD-treated KO and WT mice showed that the loss of miR-30a-5p resulted in intestinal microbiota imbalance and was highly related to the arachidonic acid metabolic pathway. Targeted metabolomic in the liver tissues unveiled upregulation of COX-related (PGF2a, 8-iso-PGF2a and PGF2) and LOX-related (LTB4, LTD4, 12S-HETE and 15S-HETE) factors in HFD-treated KO mice. Immunohistochemistry and transcriptional analyses showed that miR-30a-5p affected arachidonic acid metabolism through the LOX/COX pathways. Besides, COX/LOX pathways and hepatic steatosis were reversed after reintroducing miR-30a-5p in HFD-treated KO mice. This study reveals the pivotal mechanism by which miR-30a-5p and intestinal microbes regulate hepatic steatosis and abnormal lipid metabolism, offering promising avenues for NAFLD and atherosclerosis therapeutics. MiR-30a-5p deletion aggravated hepatic steatosis and lipid disorder induced by an HFD in mice. Gut microbiota participated in the regulation of hepatic steatosis in the context of miR-30a-5p. Gut microbiota metabolism-related arachidonic acid metabolic pathway contributed to miR-30a-5p-regulated hepatic steatosis and lipid disorder. Reintroducing miR-30a-5p reversed hepatic steatosis and arachidonic acid metabolism disorder caused by HFD and miR-30a-5p deletion.

Association of Insulin Resistance and Ectopic Fat Accumulation with HOMA Indices: A Single-Centre Observational Study

Purpose: The aim of this study was to investigate the relationship between non-alcoholic fatty liver disease (NAFLD), non-alcoholic fatty pancreas (or pancreatic) disease (NAFPD) and HOMA indices in obese patients without a diagnosis of diabetes mellitus, using ultrasound (US) as a common non-invasive diagnostic tool during routine examinations. Methods: In this single-centre, retrospective study, the records of patients who applied to the obesity outpatient clinic in 2023 were reviewed. Digital records were scanned and patients with abdominal ultrasound reports indicating age, gender, body mass index(BMI), fasting plasma glucose, fasting plasma glucose, C-peptide level and degree of pancreatic and hepatic steatosis were included in the study. Patients with known chronic disease or diabetes mellitus and patients with specific drug use were excluded from the study. Homa indices were calculated using fasting plasma glucose and C-peptide levels. Results: A total of 62 patients were included. Body mass index was 39.1, 91% had NAFLD and 82% had NAFPD. There was a significant positive correlation between BMI and NAFLD and NAFPD. HOMA scores revealed a statistically significant impact of NAFLD on insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-S) but not on beta-cell function (HOMA-B). No significant effect of NAFPD on HOMA scores was observed. Conclusion: The findings underline the association between NAFLD and insulin resistance and highlight the metabolic burden of ectopic fat deposition in obese patients. In contrast, there was no significant correlation between NAFPD and either insulin resistance or beta-cell function, suggesting that the metabolic impact of pancreatic steatosis may be different. These findings may help to guide clinical strategies for detecting and treating metabolic disorders in obesity.

Multiparametric liver assessment in patients successfully treated for hepatitis C: a 4-year follow-up

Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, in which liver stiffness increases. Liver stiffness measurements (LSM) are therefore essential in diagnosing liver diseases and predicting disease development. The study objective was to perform a comprehensive prospective assessment of the liver before, after and 4 years after treatment for HCV, including an assessment of the long-term outcome of fibrosis, steatosis and inflammation. Methods and findings Patients eligible for HCV treatment were included prospectively in 2018 (n = 47). Liver stiffness was measured using transient elastography and 2D shear-wave elastography (SWE). Blood tests, B-mode ultrasound (US) and SWE, were performed before, after (end of treatment [EOT]), 3 months after (EOT3) and 4 years after treatment (4Y). At the final visit, we added attenuation imaging and shear-wave dispersion slope (SWDS) measurements to assess steatosis and inflammation. Three months after treatment, the sustained virologic response rate was 93%. The median liver stiffness for baseline, EOT, EOT3 and 4Y was 8.1, 5.9, 5.6 and 6.3 kPa, respectively. There was a significant reduction in liver stiffness from baseline to EOT, and from EOT to EOT3. After 4 years, the mean attenuation coefficient (AC) was 0.58 dB/cm/MHz, and the mean SWDS value was 14.3 (m/s)/kHz. Conclusion The treatment for HCV was highly effective. Measurements of liver stiffness decreased significantly after treatment and remained low after 4 years. AC measurements indicated low levels of liver steatosis. Shear-wave dispersion values indicated inflammation of the liver, but the clinical implication is undetermined and should be explored in larger studies. Clinicaltrials.gov: NCT03434470 Abbreviations AC: attenuation coefficient; APRI: aspartate aminotransferase to platelet ratio index; ATI: attenuation imaging; cACLD: compensated advanced chronic liver disease; CAP: controlled attenuation parameter; FIB-4: Fibrosis-4 Index for liver fibrosis; HCC: hepatocellular carcinoma; LSM: liver stiffness measurement; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; SWDS: shear-wave dispersion slope; SWE: shear-wave elastography; US: ultrasound

Elevated ALT/AST ratio as a marker for NAFLD risk and severity: insights from a cross-sectional analysis in the United States.

The prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population. We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD. Among 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302.A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters. A higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD.

Mechanisms of high cardiovascular risk in patients with nonalcoholic fatty liver disease

Aim. To optimise the curation of patients with a comorbid course of nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) to explore pathogenetically-based targets of high cardiovascular risk (CVR) formation. Materials and methods. An open comparative study was conducted with the formation of a cohort of 126 patients with comorbid course of NAFLD and CVD with different stages of liver fibrosis, who were divided into comparison groups according to SCORE-2 and SCORE-2-OR. Collection of complaints, medical and life history, examination, general laboratory investigations and examination of hormonal status, abdominal ultrasound, EchoCG and liver elastometry to assess the severity of fibrosis were performed. Work with the study data and graphical analysis was performed using Microsoft Office 2019 software package statistical analysis using STATISTICA 12.0. Results. SCORE-2 risk increased with increasing age of patients (z=-5.29; p0.01). The most common non-cardiovascular co-morbidities in the study sample were cholelithiasis in 35 (66.78%) patients. Soluble leptin receptor levels were lower (z=-8.60; p0.01) and leptin resistance index was higher (z=-5.95; p0.01) in the higher cardiovascular group. Corresponding data were also obtained when the changes in insulin resistance index were calculated and analysed (z=-2.15; p0.01). Fibrosis stage was higher, in patients with higher CVR (z=-3.488; p0.01), while no statistically significant difference in steatosis level was recorded. According to transient elastometry, patients taking statins had lower levels of fibrosis (z=-3.747; p0.01) and hepatic steatosis (z=-3.379; p0.01). Conclusions. The most common pathology is arterial hypertension. Gallstone disease and type 2 diabetes mellitus are often found in patients with a comorbid course. The risk of comorbid pathology and CVD increases with age. Formation of advanced stages of liver fibrosis, hyperinsulinaemia and leptin resistance phenomenon are associated with higher CVR according to SCORE-2 and SCORE-2-OR. The syndrome of increased intestinal permeability is a possible mechanism of increased CVD in patients with NAFLD.

LiverColor: An Artificial Intelligence Platform for Liver Graft Assessment.

Hepatic steatosis, characterized by excess fat in the liver, is the main reason for discarding livers intended for transplantation due to its association with increased postoperative complications. The current gold standard for evaluating hepatic steatosis is liver biopsy, which, despite its accuracy, is invasive, costly, slow, and not always feasible during liver procurement. Consequently, surgeons often rely on subjective visual assessments based on the liver's colour and texture, which are prone to errors and heavily depend on the surgeon's experience. The aim of this study was to develop and validate a simple, rapid, and accurate method for detecting steatosis in donor livers to improve the decision-making process during liver procurement. We developed LiverColor, a co-designed software platform that integrates image analysis and machine learning to classify a liver graft into valid or non-valid according to its steatosis level. We utilized an in-house dataset of 192 cases to develop and validate the classification models. Colour and texture features were extracted from liver photographs, and graft classification was performed using supervised machine learning techniques (random forests and support vector machine). The performance of the algorithm was compared against biopsy results and surgeons' classifications. Usability was also assessed in simulated and real clinical settings using the Mobile Health App Usability Questionnaire. The predictive models demonstrated an area under the receiver operating characteristic curve of 0.82, with an accuracy of 85%, significantly surpassing the accuracy of visual inspections by surgeons. Experienced surgeons rated the platform positively, appreciating not only the hepatic steatosis assessment but also the dashboarding functionalities for summarising and displaying procurement-related data. The results indicate that image analysis coupled with machine learning can effectively and safely identify valid livers during procurement. LiverColor has the potential to enhance the accuracy and efficiency of liver assessments, reducing the reliance on subjective visual inspections and improving transplantation outcomes.

Metabolic effects of physical exercise on zebrafish (Danio rerio) fed a high-fat diet.

The present study aimed to establish zebrafish as an experimental model for investigations into obesity and physical exercise, as well as to assess the effects of these factors on metabolism. The experiment spanned twelve weeks, comprising a feeding trial during which the last four weeks incorporated a physical exercise protocol. This protocol involved placing fifteen animals in a five-liter aquarium, where they were subjected to swimming at an approximate speed of 0.08m/s for 30min daily. Throughout the experiment, histological analyses of visceral, subcutaneous, and hepatic adipose tissues were conducted, along with biochemical analyses of total cholesterol and its fractions, triglycerides, glucose, lactate, and alanine aminotransferase (ALT) levels. Additionally, oxidative stress markers, such as reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and catalase activity and the formation of thiobarbituric acid-reactive substances, were investigated. The results revealed that the group fed a high-fat diet exhibited an increase in ROS production and SOD activity. In contrast, the group administered the high-fat diet and subjected to physical exercise demonstrated a notable reduction in visceral adipocyte area, hepatic steatosis levels, ALT levels, and SOD activity. These findings indicate that physical exercise has a positive effect on obesity and oxidative stress in zebrafish, providing promising evidence for future investigations in this field.

Clinical Application of Infrared Spectroscopy in Liver Transplantation for Rapid Assessment of Lipid Content in Liver Graft

Liver transplantation (LT) is a major treatment for patients with end-stage liver diseases. Steatosis is a significant risk factor for primary graft nonfunction and associated with poor long-term graft outcomes. Traditionally, the evaluation of steatosis is based on frozen section examination to estimate the percentage of hepatocytes containing lipid vesicles. However, this visual evaluation correlates poorly with the true lipid content. This study aimed to address the potential of infrared (IR) microspectroscopy for rapidly estimating lipid content in the context of LT and assessing its impact on survival. Clinical data were collected for >20 months from 58 patients who underwent transplantation. For each liver graft, macrovacuolar steatosis and microvesicular steatosis were evaluated through histologic examination of frozen tissue section. Triglycerides (TG) were further quantified using gas phase chromatography coupled with a flame ionization detector (GC-FID) and estimated by IR microspectroscopy. A linear relationship and significant correlation were observed between the TG measured by GC-FID and those estimated using IR microspectroscopy (R2 = 0.86). In some cases, microvesicular steatosis was related to high lipid content despite low levels of macrovacuolar steatosis. Seven patients experienced posttransplantation liver failure, including 5 deceased patients. All patients underwent transplantation with grafts containing significantly high TG levels. A concentration of 250 nmol/mg was identified as the threshold above which the risk of failure after LT significantly increased, affecting 35% of patients. Our study established a strong correlation between LT outcomes and lipid content. IR microspectroscopy proved to be a rapid and reliable approach for assessing the lipid content in clinical settings.

Calebin A attenuated inflammation in RAW264.7 macrophages and adipose tissue to improve hepatic glucose metabolism and hyperglycemia in high-fat diet-fed obese mice

The increased incidence of obesity, which become a global health problem, requires more functional food products with minor side and excellent effects. Calebin A (CbA) is a non-curcuminoid compound, which is reported to be an effective treatment for lipid metabolism and thermogenesis. However, its ability and mechanism of action in improving obesity-associated hyperglycemia remain unclear. This study was designed to explore the effect and mechanism of CbA in hyperglycemia via improvement of inflammation and glucose metabolism in the adipose tissue and liver in high-fat diet (HFD)-fed mice. After 10 weeks fed HFD, obese mice supplemented with CbA (25 and 100 mg/kg) for another 10 weeks showed a remarkable reducing adiposity and blood glucose. CbA modulated M1/M2 macrophage polarization, ameliorated inflammatory cytokines, and restored adiponectin as well as Glut 4 expression in the adipose tissue. In the in vitro study, CbA attenuated pro-inflammatory markers while upregulated anti-inflammatory IL-10 in LPS + IFNγ-generated M1 phenotype macrophages. In the liver, CbA attenuated steatosis, inflammatory infiltration, and protein levels of inflammatory TNF-α and IL-6. Moreover, CbA markedly upregulated Adiponectin receptor 1, AMPK, and insulin downstream Akt signaling to improve glycogen content and increase Glut2 protein. These findings indicated that CbA may be a novel therapeutic approach to treat obesity and hyperglycemia phenotype targeting on adipose inflammation and hepatic insulin signaling.

Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer.

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B+ natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B+ NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.

Impact of dietary fiber fraction of chia seed supplementation on hepatic steatosis and other metabolic disturbances in a high-fat diet model

Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by hepatic triglyceride elevation is prevalent globally and often leads to significant consequences such as steatosis and hepatocarcinoma. In association with insulin resistance, oxidative stress, and inflammation, effective interventions are essential. Dietary fiber plays a crucial role in regulating these metabolic parameters. Chia (Salvia hispanica L.), a fiber-rich oilseed, is known for its high fiber content. This study assessed the impact of the fiber-rich fraction of partially defatted chia seeds (FFC) on hepatic steatosis and metabolic disturbances induced by a high-fat diet (HFD) in mice. Male C57BL/6J mice were fed either a control diet (CD) or HFD for 10 weeks, followed by FFC or oatmeal supplementation for an additional 4 weeks. FFC intake significantly reduced hepatic steatosis, lowered triglyceride and cholesterol levels, normalized plasma triglycerides, decreased oxidative stress, and attenuated inflammation. FFC has emerged as a promising candidate for managing hepatic steatosis.

Small intestinal bacterial overgrowth in obese patients with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: a cross-sectional study

Background/aimsThe metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are frequent comorbidities with a high prevalence worldwide. Their pathogenesis are multifactorial, including intestinal dysbiosis. The role of small intestinal bacterial overgrowth (SIBO) in MASLD progression in obese patients remains unknown. We aimed to determine the association between SIBO and the severity of MASLD in obese patients.MethodsAn observational and cross-sectional study was conducted in obese patients, diagnosed with or without MASLD by liver biopsy. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis without fibrosis (MASH-NF), MASH with fibrosis (MASH-F), or without MASLD (control subjects, CS) were identified by presence of steatosis, portal and lobular inflammation, and fibrosis. SIBO was determined by standardized lactulose breath tests.ResultsA total of 59 patients with MASLD, 16 with MASL, 20 with MASH-NF, 23 with MASH-F, and 14 CS were recruited. Higher percentages of SIBO were observed in MASLD patients (44.2%) compared to CS (14.2%; p = 0.0363). Interestingly, MASH-F showed higher percentages of SIBO (65.2%) in comparison to non-fibrotic MASLD (33.3%; p = 0.0165). The presence of SIBO was not correlated with the level of hepatic steatosis in MASLD patients.ConclusionsA positive correlation between MASLD and SIBO in obese patients was principally explained by the presence of liver fibrosis. Our findings suggest a pathogenic role of intestinal dysbiosis in the progression of MASLD. Future research will elucidate the underlying mechanisms of SIBO in MASLD advancement.

Gender Differences in Liver Steatosis and Fibrosis in Overweight and Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease before and after 8 Weeks of Very Low-Calorie Ketogenic Diet.

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic liver disease. Lifestyle modifications and dieting are strategies that can prevent metabolic dysfunction-associated steatotic liver disease (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD and has been recommended for people affected by obesity; we evaluated the effect of gender on steatosis and fibrosis in a cohort of 112 overweight or obese patients undergoing an eight-week treatment with a VLCKD. Differences between the genders in terms of anthropometric measures, body composition, and metabolic indicators were examined before, during, and after the nutritional intervention. At baseline, there were significant differences between men and women in terms of anthropometric parameters, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, and lipid profile. Men had considerably higher levels of liver steatosis (measured by CAP) and liver stiffness (measured by E) under basal conditions than women. After the VLCKD, there were reductions in both genders of controlled attenuation parameter (CAP), body weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, insulin resistance, fat mass (FM), free fat mass (FFM), and fasting blood glucose, insulin, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, alanine transaminase (ALT), gamma-glutamyl transferase (γGT), and uric acid levels. Only in men, liver stiffness, aspartate aminotransferase (AST), creatinine, and C-reactive protein (CRP) levels significantly decreased. Moreover, men had significantly greater levels of liver steatosis: the male gender featured an increase of 23.96 points of the Fibroscan CAP. Men exhibited higher levels of steatosis and fibrosis than women, and these differences persist despite VLCKD. These gender-specific variations in steatosis and fibrosis levels could be caused by hormonal and metabolic factors, suggesting that different therapeutic strategies might be required depending on the gender.

Evaluation of the Diagnostic Utility of Selected Serum Adipokines and Cytokines in Subjects with MASLD-A Pilot Study.

Excess adipose tissue, particularly of the visceral type, triggering chronic low-grade inflammation and altering its secretory profile, is a contributing factor to the initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the levels of selected adipokines and cytokines in individuals with normal weight and obesity, assessing their potential for diagnosing MASLD and establishing a cutoff point for body fat content associated with hepatic steatosis development. The research involved 99 participants categorized by body mass index and MASLD presence, undergoing body composition analysis, liver elastography, biochemical tests, and evaluation of adipokines and cytokines in serum. The results indicated elevated IL-6 (interleukin 6) serum levels in individuals with obesity with MASLD compared to the normal-weight group without MASLD. The multivariate regression analysis demonstrated a connection between hepatic steatosis and total adipose tissue content, VAT (visceral adipose tissue), VAT/SAT (subcutaneous adipose tissue) ratio, HOMA-IR (homeostasis model assessment of insulin resistance), IL-6, Il-1β (interleukin 1β), and MMP-2 (matrix metalloproteinase 2). Among the adipokines and cytokines examined in this study, interleukin 6 was the strongest predictor of MASLD regardless of gender. In addition, an association between the development of hepatic steatosis and higher serum IL-1β levels and higher adipose tissue was observed in women. However, further studies on a larger group of patients are needed to consider the use of these cytokines as markers of MASLD. The HOMA-IR index demonstrated potential diagnostic utility in identifying hepatic steatosis.

Hepatic lipid droplet-associated proteome changes distinguish dietary-induced fatty liver from glucose tolerance in male mice.

Fatty liver is characterized by the expansion of lipid droplets (LDs) and is associated with the development of many metabolic diseases. We assessed the morphology of hepatic LDs and performed quantitative proteomics in lean, glucose-tolerant mice compared with high-fat diet (HFD) fed mice that displayed hepatic steatosis and glucose intolerance as well as high-starch diet (HStD) fed mice who exhibited similar levels of hepatic steatosis but remained glucose tolerant. Both HFD- and HStD-fed mice had more and larger LDs than Chow-fed animals. We observed striking differences in liver LD proteomes of HFD- and HStD-fed mice compared with Chow-fed mice, with fewer differences between HFD and HStD. Taking advantage of our diet strategy, we identified a fatty liver LD proteome consisting of proteins common in HFD- and HStD-fed mice, as well as a proteome associated with glucose tolerance that included proteins shared in Chow and HStD but not HFD-fed mice. Notably, glucose intolerance was associated with changes in the ratio of adipose triglyceride lipase to perilipin 5 in the LD proteome, suggesting dysregulation of neutral lipid homeostasis in glucose-intolerant fatty liver. We conclude that our novel dietary approach uncouples ectopic lipid burden from insulin resistance-associated changes in the hepatic lipid droplet proteome.NEW & NOTEWORTHY This study identified a fatty liver lipid droplet proteome and one associated with glucose tolerance. Notably, glucose intolerance was linked with changes in the ratio of adipose triglyceride lipase to perilipin 5 that is indicative of dysregulation of neutral lipid homeostasis.

MAFLD with central obesity is associated with increased risk of colorectal adenoma and high-risk adenoma

ObjectiveTo analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma.MethodsA total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared.ResultsHigh-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P < 0.001). Logistic regression analysis revealed that age, obesity status, central obesity status, hypertension status, diabetes status, fatty liver status, smoking history, BMI, waist circumference, triglyceride level, HDL-C level, fasting blood glucose level and degree of hepatic steatosis were all independent risk factors for colorectal adenoma. Notably, MAFLD was associated with a significantly increased risk of colorectal adenoma in patients with central obesity (P < 0.001). In addition, obesity, central obesity, diabetes, fatty liver and degree of hepatic steatosis were all shown to be independent risk factors for high-risk colorectal adenoma. In addition, a greater proportion of MAFLD patients with central obesity than those without central obesity had high-risk colorectal adenoma.ConclusionMAFLD and central obesity are independently associated with the development of colorectal adenoma. MAFLD with central obesity is associated with an increased risk of colorectal adenoma and high-risk adenoma.

Abstract P407: Decreased Peripheral Mitochondrial Respiration in Pre-Adolescent Hispanic Children With Hepatic Steatosis

Introduction: Mitochondria plays a significant role in the functioning of the liver. Its function and structure have been associated with diseases outside the organelle by producing reactive oxygen species (ROS), causing generalized oxidative stress, improper function to several metabolic pathways, and perpetuating a pro-inflammatory state in conditions like obesity, diabetes, and metabolic dysfunction associated steatotic liver disease (MASLD). These diseases are on the rise and increase future atherosclerotic cardiovascular disease. Little is known regarding the pathophysiology of the earliest stages of hepatic steatosis, although mitochondrial dysfunction has been shown in later stages. In young children with and without MASLD, we aimed to measure mitochondrial respiration and compare it to hepatic steatosis and other cardiometabolic parameters. The hypothesis of the sub-study was that children with MASLD will have a decreased mitochondrial function compared with healthy children. Methods: We report data on 9 subjects, (all Latino subjects, mean age of 8.1 years, mean BMIp of 78%) who participated in screening for an ongoing clinical trial (ClinicalTrials No. NCT05292352). After consent and assent, procedures included drawing whole blood and transferring it immediately to the lab. Monocyte isolation was performed using RosetteSep™ Cocktail and measurement of fatty acid oxidation and glycolysis using the Seahorse Bioscience XFp extracellular flux analyzer. We measured the Oxygen Consumption Rate (OCR) as a proxy for mitochondrial respiration. Association with the mitochondrial parameters was evaluated with the percentage of hepatic steatosis (Hepafat), levels of ALT, insulin, and BMI percentile (BMIp). Data were analyzed using the R software program version 4.2.3 Results: Mean hepatic steatosis (HS) was 5.97% with a low of 2.4% and a high of 13%. The mean OCR for the subjects without MASLD (n=4, HS ≤5% by MRI) was 404.64 and the mean for subjects with MASLD (n=5, HS ≥5% by MRI) was 349.88. The mean OCR of subjects with a normal, overweight, and obese BMIp was 441.58, 397.45, 309.08, respectively. We found peripheral mitochondrial respiration tends to decrease as hepatic steatosis, BMIp, ALT and insulin levels increase. Conclusion: Hepatic steatosis is associated with decreased mitochondrial respiration and perhaps perpetuates an inflammatory state at very young ages in this vulnerable population. More subjects from the NAFLD prevention study will increase the significance of the study in the future.

Association of Histopathological and Biochemical Aspects of NAFLD With the Severity of Liver Fibrosis in Individuals With Obesity: Cross-sectional Study.

Given the importance of fibrosis in the progression of non-alcoholic fatty liver disease (NAFLD), identifying biochemical and histopathological aspects associated with its severity is important to determine the course of disease in high-risk populations. The study aims to investigate correlations between biochemical and histopathological variables associated with the occurrence and severity of NAFLD-related liver fibrosis in individuals with obesity. This is a cross-sectional study which enrolled 171 individuals who underwent bariatric surgery at a tertiary university hospital. Clinical, laboratory, and histopathological hepatic characteristics were analyzed. Univariate and multivariate analyses were carried out to identify factors associated with the outcomes studied (severity of fibrosis staging) through simple and multiple regression models. Female were 87.7%, and the mean age was 38.4 ± 9.3years. The most common histopathological abnormalities were macrovesicular steatosis (74.9%) and hepatocellular ballooning (40.4%). In the histopathological univariate analysis, liver fibrosis significantly correlated with severities of microvesicular steatosis (p = 0.003), lobular inflammation (p = 0.001), and NAS (p < 0.001). In the multivariate analysis, the degrees of microvesicular steatosis (p < 0.001) and NAS (p < 0.001) independently correlated with fibrosis severity. In the univariate biochemical analysis, fibrosis severity significantly correlated with levels of hemoglobin A1c (p = 0.004) and glucose (p = 0.01). In the multivariate analysis, glucose levels independently correlated with liver fibrosis degree (p = 0.007). Significant and independent associations were observed between the intensities of microvesicular steatosis, NAS, and glucose levels and the severity degree of liver fibrosis in individuals with obesity.