Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients.

BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

Effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease: Clinical implications.

In this editorial, we comment on the article by Chen et al recently published in 2024. We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase (ALT) would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease (MAFLD). This is important given the increasing prevalence of MAFLD and obesity globally. Currently, a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT. The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered, particularly as their study found that 83.12% of their study population with a diagnosis of MAFLD had a normal ALT. The main advantages of screening would be to identify patients and provide intervention early, the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis. However, there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered. Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity, although studies have not yet shown a significant improvement in fibrosis regression. It would also require a huge amount of resource if a reduced ALT level alone was used as criteria; it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk. Currently, there is not a good argument to recommend widespread screening with a reduced ALT level as this is unlikely to be cost-effective. This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories. Although studies previously have suggested a more pragmatic approach in screening those over the age of 60, this is likely to change with the increasing incidence of obesity within the younger age groups. The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.

Exploring non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease.

The population with metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly common worldwide. Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care. Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD, but it has associated risks and limitations. This has spurred the exploration of non-invasive diagnostics for MAFLD, especially for steatohepatitis and fibrosis. These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements, serum tests, imaging or stool metagenome profiling. However, they still need rigorous and widespread clinical validation for the diagnostic performance.

Lipoprotein Lipidomics as a Frontier in Non-Alcoholic Fatty Liver Disease Biomarker Discovery.

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics. This technology, based on the combination of chromatography and mass spectrometry, has been extensively used to explore the lipid metabolism of NAFLD. In this review, we aim to summarize the knowledge gained through lipidomics assays exploring tissues, plasma, and lipoproteins from individuals with NAFLD. Our goal is to identify common features and active pathways that could facilitate the finding of a reliable biomarker from this field. The most frequent observation was a variable decrease (1-9%) in polyunsaturated fatty acids in phospholipids and non-esterified fatty acids in NAFLD patients, both in plasma and liver. Additionally, a reduction in phosphatidylcholines is a common feature in the liver. Due to the scarcity of studies, further research is needed to properly detect lipoprotein, plasma, and tissue lipid signatures of NAFLD etiologies, and NAFLD subtypes, and to define the relevance of this technology in disease management strategies in the push toward personalized medicine.

The newly proposed plasma-glycosylated hemoglobin A1c/High-Density lipoprotein cholesterol ratio serves as a simple and practical indicator for screening metabolic associated fatty liver disease: an observational study based on a physical examination population.

BACKGROUND: Glycotoxicity and lipotoxicity are key pathophysiological mechanisms underlying the development of metabolic associated fatty liver disease (MAFLD). The primary objective of this study is to investigate the association between the newly proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein Cholesterol Ratio (HbA1c/HDL-C ratio) and the risk of MAFLD. METHODS: A study population of 14,251 individuals undergoing health examinations was included. The association between the HbA1c/HDL-C ratio and MAFLD was analyzed using multivariable logistic regression and restricted cubic spline (RCS) analysis. Exploratory analyses were conducted to assess variations in this association across subgroups stratified by gender, age, body mass index (BMI), exercise habits, drinking status, and smoking status. The discriminatory value of the HbA1c/HDL-C ratio and its components for screening MAFLD was evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 1,982 (13.91%) subjects were diagnosed with MAFLD. After adjusting for confounding factors, we found a significant positive association between the HbA1c/HDL-C ratio and MAFLD [odds ratio (OR) 1.34, 95% confidence interval (CI): 1.25, 1.44]. No significant differences in this association were observed across all subgroups (All P for interaction > 0.05). Furthermore, through RCS analysis, we observed a nonlinear positive correlation between the HbA1c/HDL-C ratio and MAFLD (P for non-linearity < 0.001), with a potential threshold effect point (approximately 3 for the HbA1c/HDL-C ratio). Beyond this threshold point, the slope of the MAFLD prevalence curve increased rapidly. Additionally, in further ROC analysis, we found that for the identification of MAFLD, the HbA1c/HDL-C ratio was significantly superior to HbA1c and HDL-C, with an area under the curve (AUC) and optimal threshold of 0.81 and 4.08, respectively. CONCLUSIONS: Our findings suggest that the newly proposed HbA1c/HDL-C ratio serves as a simple and practical indicator for assessing MAFLD, exhibiting well-discriminatory performance in screening for MAFLD.

Mapping global research trends: Nutrition associations with nonalcoholic fatty liver disease - a Scopus bibliometric analysis.

BACKGROUND: Several bibliometric analyses have been carried out to identify research hotspots and trends in nonalcoholic fatty liver disease (NAFLD) research. Nonetheless, there are still significant knowledge gaps that must be filled to advance our understanding of and ability to treat NAFLD. AIM: To evaluate, through bibliometric and visual analysis, the current status of related research, related research frontiers, and the developmental trends in the field of diet and NAFLD. METHODS: We retrieved publications about diet and NAFLD published between 1987 and 2022 from Scopus. Next, we used VOSviewer 1.6.20 to perform bibliometric analysis and visualization. RESULTS: We found a total of 1905 studies, including 1637 (85.93%) original articles and 195 (10.24%) reviews, focused on the examination of NAFLD and its correlation with diet that were published between 1987 and 2022. Among the remaining five types of documents, 38 were letters, notes, editorials, meeting minutes, or brief surveys, representing 1.99% of the total documents. The countries with the most publications on this topic were China (n = 539; 28.29%), followed by the United States (n = 379; 19.90%), Japan (n = 133; 6.98%), and South Korea (n = 127; 6.6%). According to the citation analysis, the retrieved papers were cited an average of 32.3 times and had an h-index of 106, with 61014 total citations. The two main clusters on the map included those related to: (1) Inflammation and oxidative stress; and (2) Dietary interventions for NAFLD. CONCLUSION: This was the first study to use data taken from Scopus to visualize network mapping in a novel bibliometric analysis of studies focused on diet and NAFLD. After 2017, the two domains that received the most attention were "dietary interventions for NAFL"' and "'inflammation and oxidative stress implicated in NAFLD and its correlation with diet." We believe that this study provides important information for academics, dietitians, and doctors, and that additional research on dietary interventions and NAFLD is warranted.

Methane gas in breath test is associated with non-alcoholic fatty liver disease.

Although the associations between a patient's body mass index (BMI) and metabolic diseases, as well as their breath test results, have been studied, the relationship between breath hydrogen/methane levels and metabolic diseases needs to be further clarified. We aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders, such as diabetes mellitus, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD), and their key risk factors. An analysis was performed using the medical records, including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. The patients were grouped according to four different criteria for LBT hydrogen and methane levels. Of 441 patients, 325 (72.1%) had positive results for methane only (hydrogen < 20 parts per million [ppm] and methane ⩾ 3 ppm). BMIs and NAFLD prevalence were higher in patients with only methane positivity than in patients with hydrogen and methane positivity (hydrogen ⩾ 20 ppm and methane ⩾ 3 ppm). According to a multivariate analysis, the odds ratio of only methane positivity was 2.002 (95% confidence interval [CI]: 1.244-3.221,P= 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas on the breath tests has the potential to be an easily measurable biomarker for NAFLD diagnosis.

[Triglyceride-glucose index in non-obese individuals: its association with and predictive value for non-alcoholic fatty liver disease].

OBJECTIVE: To investigate the association of triglyceride-glucose index (TyG) with non-alcoholic fatty liver disease (NAFLD) and its diagnostic value for NAFLD in non-obese individuals. METHODS: We retrospectively collected the data of non-obese individuals (BMI < 25 kg/m2) undergoing routine health examination at Second Affiliated Hospital of Xi'an Jiaotong University between May, 2020 and December, 2023, who all received abdominal ultrasound examination for NAFLD screening. The nonlinear relationship between TyG and non-obese NAFLD was explored using restricted cubic splines (RCS), and LASSO regression was used for variable screening; the correlation between TyG and NAFLD risk was analyzed using multivariate logistic regression. The diagnostic value of TyG for non-obese NAFLD was assessed using receiver-operating characteristic (ROC) curves and sensitivity analysis. RESULTS: A total of 3723 non-obese subjects were enrolled in this study, including 432 (11.6%) patients with NAFLD. Compared with the healthy individuals, the patients with NAFLD had significant elevations of systolic and diastolic blood pressures, total cholesterol, triglycerides, LDL-C, blood uric acid, fasting blood glucose, and TyG index and a decreased HDL-C level (P < 0.05). Multivariate logistic regression revealed that for each one-unit increase of TyG, the risk of non-obese NAFLD increased by 2.2 folds (OR=3.22, 95% CI: 2.53-4.12, P < 0.001). Compared with a TyG index in the lowest quartile Q1, a TyG index in the Q2, Q3 and Q4 quartiles was associated with an increased risk of NAFLD by 1.52 folds (OR=2.52, 95% CI: 1.20-5.95), 3.56 folds (OR=4.56, 95% CI: 2.28-10.46), and 8.66-folds (OR=9.66, 95% CI: 4.83-22.18), respectively. The RCS curve demonstrated a significant linear correlation between TyG index and non-obese NALFD risk (P for nonlinear= 0.019). For diagnosing non-obese NALFD, TyG index had an area under ROC curve of 0.819 with a sensitivity of 78.0% and a specificity of 71.2%. CONCLUSION: An increase of TyG index is correlated with increased risks of NAFLD in non-obese individuals and can serve as an indicator for screening early NAFLD in healthy individuals.

SomaLogic proteomics reveals new biomarkers and provides mechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH).

Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH) are major metabolic diseases with increasing global prevalence and no approved therapies. There is a mounting need to develop biomarkers of diagnosis, prognosis and treatment response that can effectively replace current requirements for liver biopsies, which are invasive, error-prone and expensive. We performed SomaLogic serum proteome profiling with baseline (n = 231) and on-treatment (n = 72, Weeks 12 and 16, Placebo and 25 mg PF-05221304) samples from a Phase 2a trial (NCT03248882) with Clesacostat (PF-05221304), an acetyl coA carboxylase inhibitor (ACCi) in patients with NAFLD/NASH. SomaSignal NASH probability scores and expression data for 7000+ analytes were analyzed to identify potential biomarkers associated with baseline clinical measures of NAFLD/NASH [Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] as well as biomarkers of treatment response to ACCi. SomaSignal NASH probability scores identified biopsy-proven/clinically defined NIT-based (Presumed) NASH classification of the cohort with > 70% agreement. Clesacostat-induced reduction in steatosis probability scores aligned with observed clinical reduction in hepatic steatosis based on MRI-PDFF. We identify a set of 69 analytes that robustly correlate with clinical measures of hepatic inflammation and steatosis (MRI-PDFF, ALT and AST), 27 of which were significantly reversed with ACC inhibition. Clesacostat treatment dramatically upregulated Wnt5a protein and Apolipoproteins C3 and E, with drug-induced changes significantly correlating to changes on MRI-PDFF. Our data demonstrate the utility of SomaLogic- analyte panel for diagnosis and treatment response in NAFLD/NASH and provide potential new mechanistic insights into liver steatosis reduction, inflammation and serum triglyceride elevation with ACC inhibition. (Clinical Trial Identifier: NCT03248882).

Why MASLD Lags Behind MAFLD: A Critical Analysis of Diagnostic Criteria Evolution in Metabolic Dysfunction-Associated Liver Diseases.

Emerging in the 1800s under the label "fat in the liver" and later gaining prominence in the 1980 as non-alcoholic fatty liver disease (NAFLD), the disease predominantly attributed to metabolic dysfunction presents a formidable health issue marked by substantial morbidity and mortality. It was 2020 when a change of one letter "NAFLD" to metabolic dysfunction-associated fatty liver disease "MAFLD" linked with the change in the definition and diagnostic criteria began a new controversy around the globe. Metabolic dysfunction-associated fatty liver disease (MAFLD) criteria represent a substantial departure from previous diagnostic measures of NAFLD, and provide the first set of positive criteria for diagnosis of the disease in adults and children that emphasise the key attribute of metabolic dysfunction in the pathogenesis, and acknowledges that the disease is a continuum across the life span. In 2023, an adapted version of the diagnostic criteria of MAFLD was proposed to define a slightly modified term; metabolic dysfunction-associated steatotic liver disease (MASLD). The MASLD criteria did not provide any conceptual advantage, and emerging evidence suggests that it actually performs worse than the MAFLD criteria. This raises the intriguing question of why MASLD was unable to take advantage of being second? In this review, we will explore the possible reasons for this unique case and highlight the current evidence supporting the use of MAFLD instead of MASLD in defining metabolic dysfunction-associated fatty liver diseases.

Survey of physicians' knowledge about pediatric nonalcoholic fatty liver disease in China.

OBJECTIVES: To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. METHODS: The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. RESULTS: Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. CONCLUSIONS: Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.

Usefulness of Body Fat and Visceral Fat Determined by Bioimpedanciometry versus Body Mass Index and Waist Circumference in Predicting Elevated Values of Different Risk Scales for Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Obesity constitutes a public health problem worldwide and causes non-alcoholic fatty liver disease (MALFD), the leading cause of liver disease in developed countries, which progresses to liver cirrhosis and liver cancer. MAFLD is associated with obesity and can be evaluated by validated formulas to assess MAFLD risk using different parameters such as the body mass index (BMI) and waist circumference (WC). However, these parameters do not accurately measure body fat. As MAFLD is strongly associated with obesity, we hypothesize that measuring body and visceral fat by electrical bioimpedance is an efficient method to predict the risk of MAFLD. The objective of our work was to demonstrate that electrical bioimpedance is a more efficient method than the BMI or WC to predict an elevated risk of MAFLD. METHODS: A cross-sectional, descriptive study involving 8590 Spanish workers in the Balearic Islands was carried out. The study's sample of employees was drawn from those who underwent occupational medicine examinations between January 2019 and December 2020. Five MAFLD risk scales were determined for evaluating very high levels of body fat and visceral fat. The determination of body and visceral fat was performed using bioimpedanciometry. Student's t-test was employed to ascertain the mean and standard deviation of quantitative data. The chi-square test was used to find prevalences for qualitative variables, while ROC curves were used to define the cut-off points for body and visceral fat. The calculations included the area under the curve (AUC), the cut-off points along with their Youden index, sensitivity, and specificity. Correlation and concordance between the various scales were determined using Pearson's correlation index and Cohen's kappa, respectively. RESULTS: As both total body fat and visceral fat increase, the risk of MAFLD increases with a statistically significant result (p < 0.001), presenting a higher risk in men. The areas under the curve (AUC) of the five scales that assess overweight and obesity to determine the occurrence of high values of the different MAFLD risk scales were very high, most of them exceeding 0.9. These AUC values were higher for visceral and body fat than for the BMI or waist circumference. FLD-high presented the best results in men and women with the AUC at around 0.97, both for visceral fat and total body fat, with a high Youden index in all cases (women body fat = 0.830, visceral fat = 0.892; men body fat = 0.780, visceral fat = 0.881). CONCLUSIONS: In our study, all the overweight and obesity scales show a very good association with the scales assessing the risk of MAFLD. These values are higher for visceral and body fat than for waist circumference and the BMI. Both visceral fat and body fat are better associated than the BMI and waist circumference with MAFLD risk scales.

Six-month supplementation with high dose coenzyme Q10 improves liver steatosis, endothelial, vascular and myocardial function in patients with metabolic-dysfunction associated steatotic liver disease: a randomized double-blind, placebo-controlled trial.

BACKROUND: Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) has been associated with increased cardiovascular risk. The aim of this Randomized Double-blind clinical Trial was to evaluate the effects of coenzyme-Q10 supplementation in patients with MASLD in terms of endothelial, vascular and myocardial function. METHODS: Sixty patients with MASLD were randomized to receive daily 240 mg of coenzyme-Q10 or placebo. At baseline and at 6-months, the a)Perfused boundary region of sublingual vessels using the Sideview Darkfield imaging technique, b)pulse-wave-velocity, c)flow-mediated dilation of the brachial artery, d)left ventricular global longitudinal strain, e)coronary flow reserve of the left anterior descending coronary artery and f)controlled attenuation parameter for the quantification of liver steatosis were evaluated. RESULTS: Six months post-treatment, patients under coenzyme-Q10 showed reduced Perfused boundary region (2.18 ± 0.23vs.2.29 ± 0.18 µm), pulse-wave-velocity (9.5 ± 2vs.10.2 ± 2.3 m/s), controlled attenuation parameter (280.9 ± 33.4vs.304.8 ± 37.4dB/m), and increased flow-mediated dilation (6.1 ± 3.8vs.4.3 ± 2.8%), global longitudinal strain (-19.6 ± 1.6vs.-18.8 ± 1.9%) and coronary flow reserve (3.1 ± 0.4vs.2.8 ± 0.4) compared to baseline (p < 0.05). The placebo group exhibited no improvement during the 6-month follow-up period (p > 0.05). In patients under coenzyme-Q10, the reduction in controlled attenuation parameter score was positively related to the reduction in Perfused boundary region and pulse wave velocity and reversely related to the increase in coronary flow reserve and flow-mediated dilation (p < 0.05 for all relations). CONCLUSIONS: Six-month treatment with high-dose coenzyme-Q10 reduces liver steatosis and improves endothelial, vascular and left ventricle myocardial function in patients with MASLD, demonstrating significant improvements in micro- and macro-vasculature function. TRIAL REGISTRATION: NCT05941910.

Association of triglyceride glucose-related parameters with all-cause mortality and cardiovascular disease in NAFLD patients: NHANES 1999-2018.

BACKGROUND: The relationship between the triglyceride-glucose (TyG) index and its derived index, the triglyceride glucose-waist height ratio (TyG-WHtR), with mortality and cardiovascular diseases (CVDs) in patients with non-alcoholic fatty liver disease (NAFLD) remains unclear. METHODS: This study enrolled 6627 adults aged 18 and above diagnosed NAFLD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018). Binary weighted logistic regression analyses, cox proportional hazards model and restricted cubic spline (RCS) were used to analyze the relationship between TyG and TyG-WHtR with all-cause mortality, CVD mortality and CVDs. Mediation analysis explored the mediating role of glycohemoglobin, insulin and hypertension in the above relationships. Meanwhile, the incremental predictive value of the TyG index and TyG-WHtR was further assessed. RESULTS: Except for no significant association between the TyG index and both all-cause mortality and chronic heart failure (CHF), both TyG and TyG-WHtR exhibited significant positive correlations or trends of positive correlation with all-cause mortality, CVD mortality, total-CVD, CHF, coronary heart disease (CHD) and angina pectoris. For all-cause mortality, CVD mortality and CHF, TyG-WHtR was a better predictor than TyG (TyG-WHtR: HR 1.31, 95%CI 1.03-1.66; HR 2.22, 95%CI 1.42-3.47; OR 3.99, 95%CI 1.79-8.93). In contrast, TyG index demonstrated a stronger association with total-CVD, CHD and angina pectoris (TyG index: OR 2.00, 95%CI 1.26-3.18; OR 1.85, 95%CI 1.19-2.91; OR 2.93, 95%CI 1.23-7.00). RCS analysis showed that after adjusting for covariates, most of the aforementioned relationships were linear(P overall < 0.0001, P-nonlinear > 0.05), while the associations of the TyG index and TyG-WHtR with all-cause mortality and CHF were non-linear(P overall < 0.0001, P nonlinear < 0.05). The addition of the TyG index and TyG-WHtR to the basic model for outcomes improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value. CONCLUSIONS: The predictive value of TyG or TyG-WHtR for all-cause mortality and cardiovascular risk in NAFLD patients was significant. The TyG index and TyG-WHtR might be valid predictors of cardiovascular outcomes of patients with NAFLD.

CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there is no effective drug treatment. Atherosclerosis (AS) is caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, and NASH can also elevate the risk of AS, causing a higher morbidity and mortality rate for atherosclerotic heart disease. Therefore, timely detection and diagnosis of NASH and AS are particularly important. In this study, differential gene expression analysis and weighted gene co-expression network analysis were performed on the AS (GSE100927) and NASH (GSE89632) datasets to obtain common crosstalk genes, respectively. Then, candidate Hub genes were screened using four topological algorithms and externally validated in the GSE43292 and GSE63067 datasets to obtain Hub genes. Furthermore, immune infiltration analysis and gene set variation analysis were performed on the Hub genes to explore the underlying mechanisms. The DGIbd database was used to screen candidate drugs for AS and NASH. Finally, a NASH model was constructed using free fatty acid-induced human L02 cells, an AS model was constructed using lipopolysaccharide-induced HUVECs, and a co-morbidity model was constructed using L02 cells and HUVECs to verify Hub gene expression. The result showed that a total of 113 genes common to both AS and NASH were identified as crosstalk genes, and enrichment analysis indicated that these genes were mainly involved in the regulation of immune and metabolism-related pathways. 28 candidate Hub genes were screened according to four topological algorithms, and CXCL9, IL2RB, and SPP1 were identified as Hub genes after in vitro experiments and external dataset validation. The ROC curves and SVM modeling demonstrated the good diagnostic efficacy of these three Hub genes. In addition, the Hub genes are strongly associated with immune cell infiltration, especially macrophages and γ-δ T cell infiltration. Finally, five potential therapeutic drugs were identified. has-miR-185 and hsa-miR-335 were closely related to AS and NASH. This study demonstrates that CXCL9, IL2RB, and SPP1 may serve as potential biomarkers for the diagnosis of the co-morbidity patterns of AS and NASH and as potential targets for drug therapy.

[Interpretation of the 2024 American Diabetes Association guidelines for the comprehensive management of non-alcoholic fatty liver disease combined with diabetes mellitus].

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease in adults with type 2 diabetes mellitus (T2DM) and prediabetes. Therefore, T2DM/NAFLD patient populations are at high risk for cardiovascular disease. The occurrence and progression of non-alcoholic fatty liver disease-related liver fibrosis and cardiovascular disease have a severe impact on the patient's prognosis and mortality rate. The American Diabetes Association's 2024 "Guidelines for the Standardized Management of Diabetes" put forward recommendations relevant to the screening, evaluation, treatment, and management of NAFLD in T2DM and prediabetic populations, as well as liver fibrosis. The important measures for decelerating liver inflammation and fibrosis progression and the risk of cardiovascular disease are based on improvements in lifestyle methods, weight loss, and blood sugar control.

Relationship between Vitamin D Concentration and Lipid Concentration in Patients with NAFLD in the Hulunbuir Region of China.

BACKGROUND: We aimed to characterize the relationship between the serum 25-hydroxyvitamin D concentration and the circulating lipid concentrations of patients with NAFLD in the Hulunbuir region of China. METHODS: One hundred fifty-six patients, who were diagnosed with NAFLD in the Physical Examination Department of the Second Clinical College of Inner Mongolia University for the Nationalities between January 2021 and March 2023, were recruited as NAFLD group, and 160 healthy people were recruited as a control group during the same period. The serum 25(OH)VitD, TBIL, TG, TC, LDL-C, HDL-C, AST, ALT, GGT, and FPG activities of the participants were measured, and hepatic ultrasonography was performed. RESULTS: The BMI of the NAFLD group was higher than of the control group (p < 0.05). The serum 25(OH)VitD3 (p < 0.05) and the HDL-C concentrations of the NAFLD group were lower than those of the normal control group. However, the AST (p < 0.05), ALT (p < 0.05), and GGT (p < 0.05) activities, and the serum TG (p < 0.05), TC (p < 0.05), LDL-C (p < 0.05), and the fasting glucose (p < 0.05) concentrations of the NAFLD group were higher than those of the normal control group. The serum 25(OH)VitD3 concentrations of the NAFLD group significantly cor-related negatively with BMI (r = -0.302, p < 0.01), TG (r = -0.221, p < 0.05), and fasting glucose (r = -0.236, p < 0.05). The BMI, TG, and fasting glucose of vitamin D-deficient participants were higher than of the participants with adequate or insufficient levels of vitamin D (p < 0.05). Finally, the BMI of vitamin D-deficient participants was higher than of those with an adequate vitamin D status (p < 0.05). CONCLUSIONS: A deficiency of 25(OH)VitD is more common in people from the Hulunbuir region of China than elsewhere. In addition, the vitamin D status is significantly associated with NAFLD; as the serum vitamin D concentration decreases, patients with NAFLD show greater dyslipidemia and hyperglycemia and a higher BMI.

Venomous Snakebite Encounters in Liver Transplant Recipients: A Case Report and Review of Relevant Literature.

Envenomation of humans by snakes, a global health challenge, is poorly studied in liver transplant recipients. We report a case of rattlesnake envenomation in a 52-year-old female patient who had previously received a liver transplant to treat nonalcoholic steatohepatitis cirrhosis. Despite stable graft function since her transplant, she exhibited elevated liver enzymes on admission, with a mixed hepatocellular and cholestatic pattern. Treatment included CroFab Crotalidae polyvalent immune Fab (ovine) antivenom and close monitoring, with continuation of her standard immunosuppression regimen. Inpatient observation showed reduced swelling and pain but persistently elevated enzymes. Imaging indicated fatty infiltration with patent hepatic vasculature. Her liver enzymes improved spontaneously, and she was discharged after 5 days, with complete normalization of herliver enzyme levels as shown by repeated laboratory test results 1 month later. Our case emphasizes the risk of graftinjury in liver transplant recipients, as well as the need for vigilant monitoring and early antivenom administration. We urge furtherresearch to establish guidelines for optimal care in this unique population.

Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Management of non-alcoholic fatty liver disease: Lifestyle changes.

In this editorial, we commented on a recently released manuscript by Zeng et al in the World Journal of Gastroenterology. We focused specifically on lifestyle changes in patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a hepatic manifestation of the metabolic syndrome, which ultimately leads to advanced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma and affects more than 25% of the population globally. Existing therapeutic strategies against NAFLD such as pharmacologic therapies focus on liver protection, anti-inflammation, and regulating disease-related metabolic disorder symptoms. Although several drugs are in late-stage development, potent drugs against the diseases are lacking. Additionally, existing surgical approaches such as bariatric surgery are not routinely used to treat NAFLD. Intervening in patients' unhealthy lifestyles, such as weight loss through dietary changes and exercises to ameliorate patient-associated metabolic disorders and metabolic syndrome, is the first-line treatment for patients with NAFLD. With sufficient intrinsic motivation and adherence, the management of unhealthy lifestyles can reduce the severity of the disease, improve the quality of life, and increase the survival expectancy of patients with NAFLD.