BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), now known as Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), is linked to cardiovascular disease. This renaming emphasizes the role of metabolic problems. Coronary artery calcification (CAC) reflects early coronary artery disease, but data on the MAFLD-CAC link is limited. OBJECTIVE: To demonstrate the association between metabolic dysfunction-associated fatty liver disease (MAFLD) based on its criteria and coronary artery calcification, as measured by CT CAC score. METHODS: This single-center retrospective study involved adult Filipino patients who underwent CT CAC scoring between January 2021 and January 2023. Clinical and laboratory data were obtained via review of electronic records. RESULTS: This study involved 147 patients with an average age of 62 years, primarily females (57.14%), and mostly falling into the Obese-Class I category (31.29%). The most common comorbidities were hypertension (95.24%), dyslipidemia (62.59%), and diabetes mellitus (38.1%). In terms of CAC scores using the CT Agatston method, majority (30.61%) had low calcium buildup (Stage 2 with scores between 1-99). Approximately 26.53% had higher liver fat content with liver HU below 40, while 73.47% had lower liver fat content with HU equal to or greater than 40. Furthermore, 25.17% of patients with fatty livers and other risk factors were diagnosed with MAFLD, while 74.83% were not. The p-value indicated a significant difference in proportions, suggesting a lower proportion of MAFLD among those who had undergone CT CAC scoring. However, the Pearson Chi-Square statistic (4.051) and the p-value (0.256) indicated no statistically significant association between MAFLD and CT CAC. CONCLUSION The study found a notably lower proportion of MAFLD diagnoses in patients who underwent CT CAC scoring. Additionally, there was no statistically significant link between MAFLD and CT CAC.
Cardiovascular Diseases ; Coronary Artery Disease ; Fatty Liver, Alcoholic

BACKGROUND

Non-Alcoholic Fatty Liver Disease (NAFLD) is common in Type 2 Diabetes Mellitus (T2DM). The FIB-4 index is one of the most-studied non-invasive biomarkers that combines age and laboratory parameters (platelet count, alanine-and aspartate- aminotransferase) to evaluate underlying hepatic fibrosis. This study aims to determine the diagnostic value of Fibrosis-4 (FIB-4) index scoring in screening for non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus, which is a high-risk population in development of advance fibrosis.

A single center, analytical cross-sectional study was conducted among adult T2DM patients with and without NAFLD seen at the Out-Patient Department (OPD) and those with NAFLD enrolled under the Liver Disease Databank of the Liver Disease and Transplant Center in collaboration with Research and Biotechnology Division at St. Luke’s Medical Center, Quezon City. Medical history was obtained by reviewing charts of eligible patients using data collection form. Liver ultrasound was used as the reference standard in the diagnosis of NAFLD. The FIB-4 index was calculated with this formula: age (years) x AST (U/L)/(platelets (10^9/L) x ALT (U/L)^1/2.

A total of 305 adult patients with type 2 diabetes mellitus were included in the study. The prevalence of non-alcoholic fatty liver disease based on ultrasound among diabetic patients is 76.07%. The median age (p = 0.0204), AST (p < 0.00001), ALT (p < 0.00001) were significantly higher in patients with NAFLD than those without. Platelet count (p = 0.0002) was significantly lower in patients with NAFLD than those without. The proportion of patients with low platelet count, high AST and high ALT were significantly higher in patients with NALFD than those without. In this study, the FIB-4 index cutoff score for screening of NAFLD is ≥0.76, which has an accuracy of 66.23%, sensitivity of 75%, specificity of 38.3%, PPV of 79.46% and NPV of 32.56% in detecting fatty liver.

A FIB-4 index value of ≥0.76 has an acceptable sensitivity for screening NAFLD even in the absence of fibrosis among patients with T2DM. However, due to its low specificity, additional tests to establish NAFLD diagnosis may be required.

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with Type 2 Diabetes Mellitus (T2DM) and is associated with chronic kidney disease (CKD). The aim of this cross-sectional study was to determine the association of Fibrosis-4 (FIB-4) index with CKD among T2DM patients with concomitant NAFLD.

A single center, analytical cross-sectional study was conducted among 216 T2DM patients with concomitant NAFLD. Clinical data were obtained via retrospective review of medical charts. The outcome of interest was CKD which was based on self-report obtained from medical charts or estimated Glomerular Filtration Rate (eGFR) < 60mL/min result nearest to the date of liver ultrasound. FIB-4 index of patient on admission was calculated using an online calculator and subjects were grouped into low, moderate and high risk of developing severe fibrosis depending on their FIB-4 index. In order to determine the association between FIB-4 index and CKD, logistic regression analysis was performed.

Higher FIB-4 index was found to be significantly associated with CKD. Patients with FIB-4 index of 1.45-3.25 (moderate risk) and > 3.25 (high risk) have about 3 times higher odds of CKD. However, after controlling for the significant confounders, only those who belong to high-risk group was found to be associated with CKD.

This study has demonstrated that FIB4 index > 3.25, an index of liver fibrosis, is significantly associated with development of CKD in T2DM patients with concomitant NAFLD.

OBJECTIVE: Prunella vulgaris L. has long been used for liver protection according to traditional Chinese medicine theory and has been proven by modern pharmacological research to have multiple potential liver-protective effects. However, its effects on non-alcoholic steatohepatitis (NASH) are currently uncertain. Our study explores the effects of P. vulgaris polysaccharides on NASH and intestinal homeostasis. METHODS: An aqueous extract of the dried fruit spikes of P. vulgaris was precipitated in an 85% ethanol solution (PVE85) to extract crude polysaccharides from the herb. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was administrated to male C57BL/6 mice to establish a NASH animal model. After 4 weeks, the PVE85 group was orally administered PVE85 (200 mg/[kg·d]), while the control group and CDAHFD group were orally administered vehicle for 6 weeks. Quantitative real-time polymerase chain reaction analysis, Western blotting, immunohistochemistry and other methods were used to assess the impact of PVE85 on the liver in mice with NASH. 16S rRNA gene amplicon analysis was employed to evaluate the gut microbiota abundance and diversity in each group to examine alterations at various taxonomic levels. RESULTS: PVE85 significantly reversed the course of NASH in mice. mRNA levels of inflammatory mediators associated with NASH and protein expression of hepatic nucleotide-binding leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) were significantly reduced after PVE85 treatment. Moreover, PVE85 attenuated the thickening and cross-linking of collagen fibres and inhibited the expression of fibrosis-related mRNAs in the livers of NASH mice. Intriguingly, PVE85 restored changes in the gut microbiota and improved intestinal barrier dysfunction induced by NASH by increasing the abundance of Actinobacteria and reducing the abundance of Proteobacteria at the phylum level. PVE85 had significant activity in reducing the relative abundance of Clostridiaceae at the family levels. PVE85 markedly enhanced the abundance of some beneficial micro-organisms at various taxonomic levels as well. Additionally, the physicochemical environment of the intestine was effectively improved, involving an increase in the density of intestinal villi, normalization of the intestinal pH, and improvement of intestinal permeability. CONCLUSION PVE85 can reduce hepatic lipid overaccumulation, inflammation, and fibrosis in an animal model of CDAHFD-induced NASH and improve the intestinal microbial composition and intestinal structure. Please cite this article as: Zhu MJ, Song YJ, Rao PL, Gu WY, Xu Y, Xu HX. Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis. J Integr Med. 2025; 2025; 23(3): 297-308.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Male ; Dysbiosis/drug therapy* ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects* ; Polysaccharides/therapeutic use* ; Prunella/chemistry* ; Mice ; Liver/metabolism* ; Plant Extracts/therapeutic use* ; Disease Models, Animal ; Diet, High-Fat

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is the predominant form of chronic liver disease worldwide. This study was designed to investigate the proportion and characteristics of MAFLD within the general Chinese population and to identify the contributory risk factors for liver fibrosis among MAFLD individuals. METHODS: The participants were recruited from a cohort undergoing routine health evaluations at the Third Hospital of Hebei Medical University between May 2019 and March 2023. The diagnosis of MAFLD was based on the established clinical practice guidelines. The fibrosis-4 index score (FIB-4) was employed to evaluate hepatic fibrosis, with a FIB-4 score of ≥1.3 indicating significant fibrosis. Binary logistic regression analyses were used to determine risk factors associated with significant hepatic fibrosis in MAFLD. RESULTS: A total of 22,970 participants who underwent comprehensive medical examinations were included in the analysis. The overall proportion of MAFLD was 28.77% (6608/22,970), with 16.87% (1115/6608) of these patients showing significant fibrosis as assessed using FIB-4. Independent risk factors for significant liver fibrosis in MAFLD patients were male (odds ratio [OR] = 0.676, 95% confidence interval [CI]: 0.558-0.821), hepatitis B surface antigen (HBsAg) positivity (OR = 2.611, 95% CI: 1.557-4.379), body mass index ≥23.00 kg/m 2 (OR = 0.632, 95% CI: 0.470-0.851), blood pressure ≥130/85 mmHg (OR = 1.885, 95% CI: 1.564-2.272), and plasma glucose ≥5.6 mmol/L (OR = 1.815, 95% CI: 1.507-2.186) (all P <0.001). CONCLUSIONS The proportion of MAFLD in an urban Chinese population is 28.77%. About 16.87% of MAFLD patients presented with significant liver fibrosis. Independent risk factors for significant liver fibrosis in MAFLD patients should be noticed.
Humans ; Male ; Female ; Liver Cirrhosis/pathology* ; Middle Aged ; Risk Factors ; Adult ; Fatty Liver/pathology* ; Aged ; China/epidemiology* ; Logistic Models ; Urban Population ; East Asian People

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a common liver disease and may become the leading cause of severe liver disease in the future. The Global Burden of Disease (GBD) study assesses MAFLD's impact in countries and regions worldwide, providing insights into its prevalence. METHODS: Prevalence data for MAFLD from 1990 to 2021 by country and region in all sex and age groups were collected from the Global Health Data Exchange. The categorization of countries and geographic areas by development was performed using the Sociodemographic Index (SDI). RESULTS: Between 1990 and 2021, the global crude prevalence rate of MAFLD increased from 10.6% to 16.1% (beta-coefficient: 0.2%, 95% confidence interval [CI]: 0.2-0.2%, P  <0.001), and the age-standardized prevalence rate was increased from 12.1% to 15.0% (beta-coefficient: 0.1%, 95% CI: 0.1-0.1%, P  <0.001). In 2021, MAFLD was estimated to have affected 1.3 billion people worldwide. Significant uptrends were observed in all regions, super regions, and SDI categories. The fastest increase from 1990 to 2021 and the highest prevalence rate in 2021 were experienced by countries and territories with high-middle and middle SDI. An increase in the prevalence of MAFLD from 1990 to 2021 was demonstrated in all but six countries. CONCLUSIONS In 2021, the number of patients affected by MAFLD was doubled compared to 1990, and the prevalence rate increased by over 50%. The burden of MAFLD, as measured by prevalence, was more prominent in countries and territories with middle SDI and in those located in North African and Middle Eastern, possibly due to changes in lifestyle in these areas over the past 30 years.
Humans ; Global Burden of Disease ; Prevalence ; Male ; Female ; Middle Aged ; Adult ; Global Health ; Fatty Liver/epidemiology* ; Aged

BACKGROUND: Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies. METHODS: The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted. RESULTS: In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China's CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging. CONCLUSIONS The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.
Humans ; Non-alcoholic Fatty Liver Disease/mortality* ; Global Burden of Disease ; China/epidemiology* ; Prevalence ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Middle Aged ; Chronic Disease ; Adult ; Quality-Adjusted Life Years ; Liver Diseases/epidemiology* ; Aged

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

Metabolic diseases characterized by an imbalance in energy homeostasis represent a significant global health challenge. Individuals with metabolic diseases often suffer from complications related to disorders in lipid metabolism, such as obesity and non-alcoholic fatty liver disease (NAFLD). Understanding core genes involved in lipid metabolism can advance strategies for the prevention and treatment of these conditions. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism that converts saturated fatty acids into monounsaturated fatty acids. SCD1 plays a crucial regulatory role in numerous physiological and pathological processes, including energy homeostasis, glycolipid metabolism, autophagy, and inflammation. Abnormal transcription and epigenetic activation of Scd1 contribute to abnormal lipid accumulation by regulating multiple signaling axes, thereby promoting the development of obesity, NAFLD, diabetes, and cancer. This review comprehensively summarizes the key role of SCD1 as a metabolic hub gene in various (patho)physiological contexts. Further it explores potential translational avenues, focusing on the development of novel SCD1 inhibitors across interdisciplinary fields, aiming to provide new insights and approaches for targeting SCD1 in the prevention and treatment of metabolic diseases.
Stearoyl-CoA Desaturase/metabolism* ; Humans ; Metabolic Diseases/physiopathology* ; Lipid Metabolism/physiology* ; Animals ; Obesity/enzymology* ; Non-alcoholic Fatty Liver Disease

Child ; Humans ; China ; Consensus ; Fatty Liver/therapy* ; Metabolic Diseases/therapy* ; Systematic Reviews as Topic