Metabolic-associated Fatty Liver Disease Patients Research Articles

Impact of nomenclature as metabolic associated steatotic liver disease on steatotic liver disease prevalence and screening: a prospective population survey in Asians.

The introduction of the latest nomenclature, metabolic associated steatotic liver disease (MASLD), proposed by the multi-society without Asian society consensus statement, aims to redefine the diagnostic criteria for metabolic associated fatty liver disease (MAFLD). However, its effect on the epidemiology in Asia remains unclear. We conducted a population-based cross-sectional survey on fatty liver disease using multistage stratified random sampling of participants from Guangzhou, a representative area in China (ChiCTR2000033376). Demographic, socioeconomic, lifestyle, and laboratory data were collected. Hepatic steatosis and the severity of fibrosis were assessed using FibroScan. A total of 7388 individuals were recruited, the proportion of which meeting the definitions for nonalcoholic fatty liver disease (NAFLD), MAFLD, and MASLD were 2359 (31.9%), 2666 (36.1%), and 2240 (30.3%), respectively. One hundred and twenty (1.6%) patients had cryptogenic SLD, and 537 (7.3%) patients were diagnosed with MetALD. MASLD did not significantly differ from NAFLD and MAFLD, except that MAFLD patients had a lower proportion of males, hypertension, and diabetes and were less likely to consume tea (P<0.05). Both cryptogenic SLD and MASLD non-MAFLD patients exhibited milder hepatic steatosis and a lower frequency of liver injury than NAFLD, MAFLD, or MASLD patients (all P<0.05). An increased HOMA-IR (adjusted OR: 1.33, 95% CI: 1.10-2.03) was associated with higher risk of moderate-to-severe steatosis for MASLD non-MAFLD patients, while consuming more cups of tea (P for trend=0.015) showed inverse associations. Irrespective of terminology used is that fatty liver disease is highly prevalent in the Han Chinese population. Differences in insulin resistance and lifestyle risk factors are associated with redefinition disparities.

PNPLA3 I148M Promotes Fatty Liver Disease While Preserving Cardiac Health

Metabolic-associated fatty liver disease (MAFLD) and cardiovascular disease (CVD) are commonly associated comorbidities. A common genetic variant in the PNPLA3 gene, rs738409 (I148M), is the greatest genetic risk factor for development and progression of MAFLD; however, MAFLD patients expressing PNPLA3 I148M display modest protection against coronary artery disease (CAD) and adverse cardiovascular events relative to wildtype carriers. Currently, the exact mechanisms by which PNPLA3 I148M causes MAFLD and preserves cardiac health are not well understood. Previous work suggests that the variant increases susceptibility to fatty liver disease by altering hepatic lipid metabolism, which may explain a potential mechanism for its cardioprotective effects. In order to investigate how PNPLA3 I148M might increase susceptibility to MAFLD while reducing risk of CVD we expressed either human wildtype (WT) PNPLA3 or PNPLA3 I148M as well as a GFP control specifically in the livers of PNPLA3 knockout mice. Our data demonstrate that hepatic expression of PNPLA3 I148M reduces secretion of VLDL TAGs from adipose tissue derived fatty acids. In agreement with prior investigations, mice expressing PNPLA3 I148M and fed a chow diet demonstrated significant increases in hepatic accumulation of neutral lipids (triglycerides &amp; cholesterol esters) relative to WT and GFP expressing mice. Similarly, when fed a fatty liver promoting diet (D009100310) high in fructose, cholesterol, and saturated fats there remained a strong trend for greater liver to body weight ratios and hepatic TAGs in mice expressing the variant when compared to WT expressing mice (p=0.052 and p=0.071 respectively). Changes in hepatic lipid accumulation were not due to any alterations in insulin sensitivity, daily food consumption, energy expenditure or oxygen consumption between WT and I148M groups. Echocardiography revealed that hearts of mice expressing WT PNPLA3 had increases in left ventricular thickness (p=0.051) and left ventricle weights following dietary treatment that was not apparent in the I148M expressing mice. Moreover, there was a reduction in E/A ratios, a sensitive measure of diastolic functioning, in GFP and WT expressing mice post-treatment, that was not seen in the I148M mice. Overall, these findings indicate that PNPLA3 I148M promotes fatty liver, yet protects against diet-induced effects on ventricular remodeling and diastolic functioning. Our next steps will be to assess measures of atherosclerotic plaque formation around major blood vessels and investigate the metabolic pathways altered by PNPLA3 I148M. NIH R00 DK114471 NIH R01 DK126743 USDA grant no. 2021-09425 Pilot feasibility grant from University of Michigan: P30DK020572 Detroit Cardiovascular Training grant NIH 2T32HL120822. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Study of fatty acid-binding protein and Bacteroidetes and Firmicutes levels in patients with metabolic-associated fatty liver disease in combination with type 2 diabetes mellitus and small intestinal bacterial overgrowth syndrome

The aim of the study was to examine serum levels of liver and intestinal fatty acid-binding proteins (L-FABP and I-FABP), fecal numbers of Bacteroidetes (B) and Firmicutes (F) in patients with metabolic-associated fatty liver disease (MAFLD) in combination with type 2 diabetes mellitus (Т2DM) and small intestinal bacterial overgrowth (SIBO) syndrome. Materials and methods. The prospective, interventional, randomized study included 51 patients with MAFLD in combination with Т2DM, who were examined and divided into 2 groups. Group 1 consisted of 24 patients with MAFLD and Т2DM without SIBO. Group 2 was comprised of 27 patients with MAFLD in combination with Т2DM and SIBO. The control group included 20 apparently healthy individuals. Serum levels of L-FABP and I-FABP were measured by ELISA method using the Human L-FABP and I-FABP ELISA Kit test systems, respectively (Elabscience, USA). Fecal numbers of B and F were determined by real-time PCR. Bacterial DNA was detected in a thermal cycler Rotor-Gene 6000 (QIAGEN, Germany) using DNA 16S rRNA primers and NanoDrop ND-8000 reagents (Thermo Scientific, USA). Results. To assess the state of intestinal permeability, serum levels of L-FABP and I-FABP were examined and numbers of phylum F and В as well as their ratio were calculated. Patients of both groups have been found to have increased serum levels of L-FABP, I-FABP, numbers of B in fecal samples and decreased numbers of F and F/B ratio. Conclusions. The study results obtained have revealed increased intestinal permeability and demonstrated an important diagnostic value of serum L-FABP and I-FABP as a biomarker of intestinal permeability in diabetic MAFLD patients with or without SIBO. Increased fecal numbers of Bacteroidetes, decreased numbers of Firmicutes and F/B ratio have been detected in diabetic MAFLD patients with or without SIBO.

The contribution of vitamin D insufficiency to the onset of steatotic liver disease among individuals with metabolic dysfunction

The interplay between fatty liver disease (FLD) and metabolic dysfunction has given rise to the concept of metabolic associated fatty liver disease (MAFLD). With vitamin D insufficiency frequently co-occurring with FLD and linked to metabolic abnormalities, this study investigates the potential role of vitamin D in the development of MAFLD. In this cross-sectional analysis, 22,476 participants with baseline metabolic dysfunction and known serum 25-OH-vitamin D3 levels were examined. The fatty liver index (FLI) was utilized to predict FLD, dividing subjects into MAFLD and non-MAFLD groups. Further stratification by vitamin D levels (sufficient vs. insufficient) and gender provided a detailed assessment through binary logistic regression to determine the association of vitamin D status with MAFLD incidence. Vitamin D insufficiency correlated with a higher MAFLD incidence in metabolically impaired individuals. Post-adjustment, the correlation was stronger (men: aOR = 1.32, 95% CI = 1.22–1.43, P < 0.001; women: aOR = 1.53, 95% CI = 1.18–1.98, P = 0.001). Lower serum 25-OH-vitamin D3 levels were found in MAFLD patients across genders (men: P = 0.003; women: P = 0.014), with a higher prevalence of insufficiency in MAFLD cases (men: P = 0.007; women: P = 0.003). The vitamin D-MAFLD link was stable across subgroups and using varying FLI criteria. Our findings indicate a clear association between vitamin D insufficiency and increased MAFLD incidence, underscoring the potential of vitamin D as an anti-lipogenic and anti-fibrotic agent.

Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels.MethodsPublished studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression.ResultsA total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2–31.6%) and 26.2% (23.9–28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively.ConclusionsThe present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Association between remnant cholesterol and insulin resistance levels in patients with metabolic-associated fatty liver disease

The relationship between remnant cholesterol (RC) and homeostasis model assessment-insulin resistance (HOMA-IR) in the context of metabolic-associated fatty liver disease (MAFLD) remains an area of ambiguity. This investigation was designed to elucidate the potential association between RC and HOMA-IR in a cohort of American adults diagnosed with MAFLD. Data from 5533 participants were procured from the 2017–2018 US National Health and Nutrition Examination (NHANES) databases. A weighted linear regression model was employed to analyze the association between RC and HOMA-IR in the context of MAFLD. Preliminary analysis revealed that 44.67% of the participants were diagnosed with MAFLD, with a higher prevalence observed in individuals aged 50–64 years (31.84%, p < 0.0001) and in males compared to females (53.48% vs. 46.52%, p < 0.0001). A positive correlation was identified between RC and HOMA-IR in MAFLD patients. The threshold effect analysis model indicated a breakpoint at RC = 30 mg/dl, with a more pronounced positive correlation when RC < 30 mg/dl (β = 0.17, p < 0.001). Receiver operating characteristic analysis further demonstrated that among all lipid parameters, RC exhibited the largest area under the curve. The study findings suggest a positive correlation between RC and HOMA-IR in MAFLD patients, indicating that elevated RC may serve as an independent risk factor for MAFLD.

Exploring Paxlovid Efficacy in COVID-19 Patients with MAFLD: Insights from a Single-Center Prospective Cohort Study.

This study investigates the intricate interplay between Metabolic-associated Fatty Liver Disease (MAFLD) and COVID-19, exploring the impact of MAFLD on disease severity, outcomes, and the efficacy of the antiviral agent Paxlovid (nirmatrelvir/ritonavir). MAFLD, affecting a quarter of the global population, emerges as a potential risk factor for severe COVID-19, yet the underlying pathophysiological mechanisms remain elusive. This study focuses on the clinical significance of Paxlovid, the first orally bioavailable antiviral agent granted Emergency Use Authorization in the United States. Notably, outcomes from phase II/III trials exhibit an 88% relative risk reduction in COVID-19-associated hospitalization or mortality among high-risk patients. Despite conflicting data on the association between MAFLD and COVID-19 severity, this research strives to bridge the gap by evaluating the effectiveness of Paxlovid in MAFLD patients with COVID-19, addressing the scarcity of relevant studies.

Low Short-Chain-Fatty-Acid-Producing Activity of the Gut Microbiota Is Associated with Hypercholesterolemia and Liver Fibrosis in Patients with Metabolic-Associated (Non-Alcoholic) Fatty Liver Disease

The aim of this study was to investigate the short-chain fatty acid (SCFA) activity of the gut microbiota of patients with metabolic-associated fatty liver disease (MAFLD). The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas–liquid chromatography. Liver fibrosis was assessed using the FIB-4 index and elastography. Among 42 non-cirrhotic MAFLD patients, 24 had high fecal SCFA levels (group H) and 18 had low fecal SCFA levels (group L). Patients in group H had lower serum uric acid, total cholesterol, and LDL cholesterol levels but a higher BMI than those in group L. All patients in group L and only 37.9% of those in group H were found to have hypercholesterolemia. In patients with hypercholesterolemia, the level of SCFAs was lower than that in patients without hypercholesterolemia. Patients in group H had less liver fibrosis than patients in group L. A total of 50.0% of the patients in group H and 92.3% of those in group L had significant liver fibrosis (≥F2). Patients with significant liver fibrosis had lower levels of fecal SCFAs—particularly acetate and butyrate. The fecal SCFA levels were positively correlated with gamma-glutamyl transferase, total bilirubin levels, BMI, and platelet count and were negatively correlated with FIB-4, liver stiffness, serum total, and LDL cholesterol levels.

Personalized Risk Assessment of Hepatic Fibrosis after Cholecystectomy in Metabolic-Associated Steatotic Liver Disease: A Machine Learning Approach.

Metabolic Associated Fatty Liver Disease (MASLD) is a condition that is often present in patients with a history of cholecystectomy. This is because both situations share interconnected metabolic pathways. This study aimed to establish a predictive model that allows for the identification of patients at risk of developing hepatic fibrosis following this surgery, with potential implications for surgical decision-making. A retrospective cross-sectional analysis was conducted in four hospitals using a database of 211 patients with MASLD who underwent cholecystectomy. MASLD diagnosis was established through liver biopsy or FibroScan, and non-invasive test scores were included for analysis. Various Machine Learning (ML) methods were employed, with the Adaptive Boosting (Adaboost) system selected to build the predictive model. Platelet level emerged as the most crucial variable in the predictive model, followed by dyslipidemia and type-2 diabetes mellitus. FIB-4 score proved to be the most reliable non-invasive test. The Adaboost algorithm improved the results compared to the other methods, excelling in both accuracy and area under the curve (AUC). Moreover, this system holds promise for implementation in hospitals as a valuable diagnostic support tool. In conclusion, platelet level (<150,000/dL), dyslipidemia, and type-2 diabetes mellitus were identified as primary risk factors for liver fibrosis in MASLD patients following cholecystectomy. FIB-4 score is recommended for decision-making, particularly when the indication for surgery is uncertain. This predictive model offers valuable insights into risk stratification and personalized patient management in post-cholecystectomy MASLD cases.

The impact of concomitant hepatitis C virus infection on liver and cardiovascular risks in patients with metabolic-associated fatty liver disease.

Chronic hepatitis C virus (HCV)-infected patients with hepatic steatosis are excluded from the diagnosis of nonalcoholic fatty liver disease (NAFLD). The new name and diagnostic criteria of metabolic-associated fatty liver disease (MAFLD) were proposed in 2020 to replace the original term NAFLD. The clinical outcome of MAFLD patients with concomitant chronic HCV infection requires further investigation. The participants from Taiwan bio-bank cohort were included. MAFLD is defined as the presence of fatty liver, plus any of the following three conditions: overweight/obesity, type 2 diabetes, or metabolic dysfunction. The patients with positive anti-HCV were considered chronic HCV infections. The severity of liver fibrosis was determined using the fibrosis-4 index and NAFLD fibrosis score (NFS). The risk of cardiovascular disease (CVD) was assessed using intima-media thickness (IMT) or plaques of carotid duplex ultrasound. A total of 18 907 participants (age 55.79 ± 10.42; males 31.9%) were included for final analysis. The prevalence of MAFLD and chronic HCV infections were 39.2% and 2.6%, respectively. According to the status of MAFLD and chronic HCV infection, they were distributed to four groups: 'dual etiology group', 'MAFLD alone', 'HCV alone', and healthy controls. Compared with the 'MAFLD alone' group, the 'dual etiology' group had a lower frequency of the male sex, reduced levels of serum triglyceride, total cholesterol, and LDL; but overall older age, a higher percentage of hypertension history. In addition, they had higher levels of serum aspartate aminotransferase, fibrosis-4 index, and NFS; but no difference in levels of alanine aminotransferase, gamma-glutamyl transferase, fatty liver index, IMT, and the percentage of carotid plaques. Using binary logistic regression, chronic HCV infection was associated with more severe liver fibrosis, but not with carotid plaques in MAFLD patients. MAFLD patients with concomitant HCV infection, a specific phenotype of MAFLD may include a higher risk of advanced liver fibrosis, but a similar risk of atherosclerotic cardiovascular disease compared to those without.

MAFLD fibrosis score: Using routine measures to identify advanced fibrosis in metabolic-associated fatty liver disease.

Early screening may prevent fibrosis progression in metabolic-associated fatty liver disease (MAFLD). We developed and validated MAFLD fibrosis score (MFS) for identifying advanced fibrosis (≥F3) among MAFLD patients. This cross-sectional, multicentre study consecutively recruited MAFLD patients receiving tertiary care (Malaysia as training cohort [n = 276] and Hong Kong and Wenzhou as validation cohort [n = 431]). Patients completed liver biopsy, vibration-controlled transient elastography (VCTE), and clinical and laboratory assessment within 1 week. We used machine learning to select 'highly important' predictors of advanced fibrosis, followed by backward stepwise regression to construct MFS formula. MFS was composed of seven variables: age, body mass index, international normalised ratio, aspartate aminotransferase, gamma-glutamyl transpeptidase, platelet count, and history of type 2 diabetes. MFS demonstrated an area under the receiver-operating characteristic curve of 0.848 [95% CI 0.800-898] and 0.823 [0.760-0.886] in training and validation cohorts, significantly higher than aminotransferase-to-platelet ratio index (0.684 [0.603-0.765], 0.663 [0.588-0.738]), Fibrosis-4 index (0.793 [0.735-0.854], 0.737 [0.660-0.814]), and non-alcoholic fatty liver disease fibrosis score (0.785 [0.731-0.844], 0.750 [0.674-0.827]) (DeLong's test p < 0.05). MFS could include 92.3% of patients using dual cut-offs of 14 and 15, with a correct prediction rate of 90.4%, resulting in a larger number of patients with correct diagnosis compared to other scores. A two-step MFS-VCTE screening algorithm demonstrated positive and negative predictive values and overall diagnostic accuracy of 93.4%, 89.5%, and 93.2%, respectively, with only 4.0% of patients classified into grey zone. MFS outperforms conventional non-invasive scores in predicting advanced fibrosis, contributing to screening in MAFLD patients.

Lifestyle determinants as predictor of severity of metabolic associated fatty liver disease (MAFLD)

BackgroundMetabolic-associated fatty liver disease (MAFLD) is a public health issue that can result in liver cirrhosis and its complications.Aim of workAssess the dietary pattern, physical activity, and sleep quality of MAFLD patients.MethodsCross-sectional study of 77 MAFLD patients being present in the outpatient clinic of Endemic Medicine Department at Cairo University Hospital. An interview questionnaire including sociodemographic, medical history, validated food frequency questionnaire (FFQ), Pittsburg Sleep Quality Index (PSQI), and international physical activity questionnaire (IPAQ) were utilized to collect data.ResultsAmong patients, 36%, 34%, and 30% had liver steatosis grades I (mild), II (moderate), and III (severe) respectively. Waist circumference, body mass index (BMI), daily caloric and carbohydrate intake, impaired sleep quality, and low physical activity were significantly linked with steatosis grades. The independent significant predictors for MAFLD severity were waist circumference (P = 0.011, OR 1.119), poor sleep quality (P = 0.038, OR 3.871), habitual sleep efficiency (OR 3.402, 95%CI 1.403–8.252), daytime dysfunction (OR 2.487, 95%CI 1.374–4.501), and physical activity (P = 0.027, OR 4.6).ConclusionWaist circumference, poor sleep quality, habitual sleep efficiency, daytime dysfunction, and low physical activity were the real marked predictors for MAFLD severity.

Demonstration of the impact of COVID-19 on metabolic associated fatty liver disease by bioinformatics and system biology approach.

Severe coronavirus disease 2019 (COVID-19) has caused a great threat to human health. Metabolic associated fatty liver disease (MAFLD) is a liver disease with a high prevalence rate. Previous studies indicated that MAFLD led to increased mortality and severe case rates of COVID-19 patients, but its mechanism remains unclear. This study analyzed the transcriptional profiles of COVID-19 and MAFLD patients and their respective healthy controls from the perspectives of bioinformatics and systems biology to explore the underlying molecular mechanisms between the 2 diseases. Specifically, gene expression profiles of COVID-19 and MAFLD patients were acquired from the gene expression omnibus datasets and screened shared differentially expressed genes (DEGs). Gene ontology and pathway function enrichment analysis were performed for common DEGs to reveal the regulatory relationship between the 2 diseases. Besides, the hub genes were extracted by constructing a protein-protein interaction network of shared DEGs. Based on these hub genes, we conducted regulatory network analysis of microRNA/transcription factors-genes and gene - disease relationship and predicted potential drugs for the treatment of COVID-19 and MAFLD. A total of 3734 and 589 DEGs were screened from the transcriptome data of MAFLD (GSE183229) and COVID-19 (GSE196822), respectively, and 80 common DEGs were identified between COVID-19 and MAFLD. Functional enrichment analysis revealed that the shared DEGs were involved in inflammatory reaction, immune response and metabolic regulation. In addition, 10 hub genes including SERPINE1, IL1RN, THBS1, TNFAIP6, GADD45B, TNFRSF12A, PLA2G7, PTGES, PTX3 and GADD45G were identified. From the interaction network analysis, 41 transcription factors and 151 micro-RNAs were found to be the regulatory signals. Some mental, Inflammatory, liver diseases were found to be most related with the hub genes. Importantly, parthenolide, luteolin, apigenin and MS-275 have shown possibility as therapeutic agents against COVID-19 and MAFLD. This study reveals the potential common pathogenesis between MAFLD and COVID-19, providing novel clues for future research and treatment of MAFLD and severe acute respiratory syndrome coronavirus 2 infection.

Characterization of an in vitro steatosis model simulating activated de novo lipogenesis in MAFLD patients

Activated de novo lipogenesis (DNL) is the critical pathway involved in the progression of metabolic-associated fatty liver disease (MAFLD). We present an invitro steatosis model for MAFLD that induces steatosis through activated DNL. This model utilizes insulin and LXR receptor ligand T0901317, eliminating the need for fatty acid treatment. Significant increases in triglycerides (TAGs) and expression of DNL-related transcription factors were observed. Transcriptomic analysis revealed distinct gene expression profiles between the DNL and conventional oleic acid (OA)-induced steatosis model. DNL steatosis model exhibited elevated pathways related to glycolysis, cholesterol homeostasis, and bile acid metabolism, reflecting its clinical relevance to MAFLD. Moreover, C75 and JNK-IN-5A compounds effectively reduced TAG accumulation and steatosis-related protein expression in the DNL model, whereas they had no significant impact on TAG accumulation in the OA model. In conclusion, we introduce an ideal model for steatosis study, which could help in understanding the MAFLD mechanisms.

Potential tactics with certain gut microbiota for the treatment of unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) constitutes an extremely malignant form of primary liver cancer. Intricate connections linking to the immune system might be associated with the pathogenesis of HCC. Meanwhile, immunotherapy with immune checkpoint inhibitors has been established to be a favorable therapeutic possibility for advanced HCC. Although curative opportunities for advanced HCC are restricted, the immune checkpoint immunotherapy has developed as the main choice for treating HCC. However, patients with metabolic-associated fatty liver disease (MAFLD)-linked HCC might be less likely to benefit from the immunotherapy alone. The limitation of the effect of the immunotherapy might be owing to the impaired T cell activation in MAFLD patients, which could be well explained by a dysfunctional gut-liver axis. Gut microbiota and their metabolites including several bile acids could contribute to modulating the responses of the immune checkpoint immunotherapy. Roles of gut microbiota in the development of cancers have expected great interest in the latest studies. Here, an interplay between the gut and liver has been presented, which might suggest to affect the efficacy of immune checkpoint immunotherapy against HCC.

Effects of Cornus mas L. on anthropometric and biochemical parameters among metabolic associated fatty liver disease patients: Randomized clinical trial

Ethnopharmacological relevanceCornus mas L. (Cornelian cherry, CM) fruits have been utilized for decades in numerous European and Asian countries as traditional cuisine and folk medicine. CM has antioxidant, anti-diabetic, anti-inflammatory, anti-obesity, and hypolipidemic activities due to its rich bioactive compounds, and CM fruits and other parts have been used for the prevention and treatment of a diverse variety of diseases in folk medicine. Obesity, insulin resistance, and inflammation are strongly associated with metabolic-associated fatty liver disease (MAFLD), therefore, CM may be hope for MAFLD patients. Aim of the studyThe study aimed to evaluate the effect of lyophilized CM fruit powder with/without diet therapy on biochemical parameters and anthropometric measurements in patients with MAFLD. Materials and methodsThis randomized clinical trial was conducted on 87 patients with MAFLD and 21 healthy individuals. Patients were randomly assigned into 4 groups: group-1 receiving 30 g/d lyophilized CM fruit powder plus diet therapy, group-2 receiving only diet therapy, group-3 receiving only 30 g/d lyophilized CM fruit powder, and group-4 had not undertaken any pharmacological treatment and diet therapy or lyophilized CM fruit powder for 8 weeks. Biochemical parameters, and anthropometric measurements at baseline and after the intervention were taken. ResultsAfter 8 weeks of intervention, a significant decrease in body weight, body mass index, body fat mass, waist and hip circumferences, fasting blood glucose, insulin, hbA1c, liver enzymes, total triglycerides, low-density lipoprotein, total cholesterol were found in group-1, 2 and 3. ConclusionLyophilized CM fruit powder in addition to diet therapy and only diet therapy had a positive and similar effect on anthropometric measurements and biochemical parameters in MAFLD patients. Furthermore, only lyophilized CM fruit powder improved glycemic parameters. Therefore, lyophilized CM fruit powder may be beneficial for adult patients with MAFLD.

Metabolic Associated Fatty Liver Disease (MAFLD) and COVID-19 Infection: An Independent Predictor of Poor Disease Outcome?

Background and Objectives: Early reports on COVID-19 infection suggested that the SARS-CoV-2 virus solely attacks respiratory tract cells. As the pandemic spread, it became clear that the infection is multiorganic. Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease strongly associated with insulin resistance and diabetes. The aim of this study was to assess a possible interplay between MAFLD and COVID-19 infection and its implication in COVID-19 outcome. Materials and Methods: A retrospective observational study, including 130 COVID-19 positive patients was conducted. MAFLD diagnosis was made based on the International Consensus criteria. Patients were divided into two groups, group A (MAFLD) and group B (nonMAFLD). Anthropometric and laboratory analysis were obtained. COVID-19 severity was assessed using the NEWS2 score. Disease outcome was threefold and regarded as discharged, patients who required mechanical ventilation (MV), and deceased patients. Results: MAFLD prevalence was 42%, 67% of patients were discharged, and 19% needed MV. Mortality rate was 14%. MAFLD patients were significantly younger (p < 0.001), and had higher body mass index (p < 0.05), respiratory rate (p < 0.05) and systolic blood pressure (p < 0.05) than nonMAFLD patients. Regarding metabolic syndrome and inflammatory markers: group A had significantly higher glycemia at admission (p = 0.008), lower HDL-c (p < 0.01), higher triglycerides (p < 0.01), CRP (p < 0.001), IL-6 (p < 0.05) and ferritin (p < 0.05) than group B. MAFLD was associated with more prevalent type 2 diabetes (p = 0.035) and hypertension (p < 0.05). MAFLD patients had a more severe disease course (NEWS2 score, 6.5 ± 0.5 vs. 3 ± 1.0, p < 0.05). MAFLD presence was associated with lower patient discharge (p < 0.01) and increased need for MV (p = 0.024). Multiple regression analysis showed that BMI (p = 0.045), IL-6 (p = 0.03), and MAFLD (p < 0.05) are significant independent risk factors for a poor COVID-19 outcome. Conclusions: The prevalence of MAFLD is relatively high. MAFLD patients had a more severe COVID-19 clinical course and worse disease outcome. Our results imply that early patient stratification and risk assessment are mandatory in order to avoid poor outcomes.

Associations between serum GDF15 and glycolipid metabolism disorder in metabolic associated fatty liver patients

Objective: To investigate relationships between serum growth differentiation factor 15 (GDF15) and glycolipid metabolism in patients with metabolic associated fatty liver disease (MAFLD). Methods: The current investigation was a cross-sectional study. A total of 333 patients from the Fengxian District Central Hospital were recruited into the study after physical examination from February 2020 to February 2021. There were 107 patients with MAFLD and type 2 diabetes mellitus (T2DM), including 54 males and 53 females with a mean age of (57±11) years. There were 65 patients with simple MAFLD only, including 32 men and 33 women with a mean age of (49±5) years. There were 105 patients with T2DM only, including 53 men and 52 women, with a mean age of (56±10) years. A control group of 56 people without MAFLD or diabetes,28 male, 28 female, mean age (48±6) years, was also included in the study. Serum GDF15 was measured via enzyme-linked immunosorbent assays. IBM SPSS 26.0 was used for statistical analysis. Logistic regression was used to evaluate relationships between GDF15 and metabolic abnormalities in MAFLD patients. Results: GDF15 progressively increased in the control [385 (296, 484) ng/L], nonobese MAFLD [388 (319, 435) ng/L], obese MAFLD [426 (354, 527) ng/L], T2DM [664 (483, 900) ng/L], and MAFLD+T2DM groups [770 (560, 1 074) ng/L](H=113.82, P=0.001). There was no significant difference in serum GDF15 between the simple MAFLD [406 (339, 524) ng/L] and control group (U=1 505.50, P=0.132). GDF15 was significantly higher in the MAFLD+T2DM group than in the T2DM-only group (U=4 573.50, P=0.019). In logistic regression analysis increased GDF15 was associated with increased risks of simple MAFLD [odds ratio (OR)=2.202], T2DM (OR=29.656), and MAFLD+T2DM(OR=58.197). In patients with MAFLD, serum GDF15 was higher in the FIB4 index>1.45 group [773 (534, 1 162) ng/L] than in the FIB4 index<1.45 group [527 (389, 787) ng/L] (U=1 709.50, P<0.001). Increased GDF15 was associated with an increased risk of advanced liver fibrosis (OR=2.388). Conclusion: In patients with simple MAFLD, GDF15 level was not significantly higher than in the control group. In the T2DM-only group and the MAFLD+T2DM group GDF15 was significantly higher than in the control group. Increased serum GDF15 was associated with increased risk and severity of MAFLD complicated with abnormal glucose and lipid metabolism. High GDF15 increased the risk of advanced fibrosis in MAFLD patients.

The Triglyceride-Glucose Index is Associated with Vitamin D Status in Metabolic-Associated Fatty Liver Disease.

Vitamin D deficiency was thought to be associated with insulin resistance and metabolic-associated fatty liver disease (MAFLD). The aim of this study was to investigate the relationship between the triglyceride-glucose (TyG) index, a useful surrogate biomarker of insulin resistance, and vitamin D status in patients with MAFLD. A total of 566 patients with MAFLD were included in this retrospective cross-sectional study. Clinical characteristics were compared between participants with and without vitamin D deficiency. The association between the TyG index and serum 25-hydroxyvitamin D [25(OH)D] levels was determined by Spearman correlation analysis and logistic regression analysis. The receiver operating characteristic curve (ROC) was used to assess the diagnostic efficacy of TyG index for vitamin D deficiency in MAFLD patients. The TyG index levels were higher in the vitamin D deficient group than in the non-vitamin D deficient group, and serum 25(OH)D was negatively correlated with the TyG index. The TyG index was an independent risk factor for vitamin D deficiency in patients with MAFLD. The area under the curve (AUC) of the TyG index for the identification of vitamin D deficiency in MAFLD patients was 0.744 (95% CI: 0.701-0.787, p<0.001). The TyG index is negatively associated with vitamin D status in patients with MAFLD. In patients with MAFLD, a higher TyG index may be an indication of a higher prevalence of vitamin D deficiency.

Prevalence and clinical outcomes in subtypes of metabolic associated fatty liver disease

In 2020, metabolic Associated Fatty Liver Disease (MAFLD) was proposed to replace non-alcoholic fatty liver disease (NAFLD) with new diagnostic criteria. The prevalence and clinical outcomes of MAFLD subtypes remained unclear. The participants from Taiwan bio-bank cohort were included. MAFLD was defined as the presence of fatty liver, plus any of the following three conditions: overweight/obesity, diabetes mellitus (DM), or metabolic dysfunction. The patients with positive HBsAg or anti-HCV were considered as chronic HBV or HCV infection. NAFLD fibrosis score (NFS)>0.676 plus fibrosis 4 (FIB-4) score > 2.67 was defined as advanced liver fibrosis. Atherosclerosis was diagnosed as having carotid plaques on duplex ultrasounds. The clinical outcomes were assessed among four subtypes of MAFLD including DM, obesity, chronic HBV infection, and chronic HCV infection. A total of 21,885 participants (mean age 55.34±10.31; 35.69% males) were included in the final analysis. Among them, 38.83% were diagnosed with MAFLD. The prevalence of MAFLD was 66.95% in DM patients, 65.07% in obese participants, 33.74% in chronic HBV patients, and 30.23% in chronic HCV patients. Logistic regression analysis showed that the subtypes of DM and chronic HCV infection were associated with an increased risk of advanced liver fibrosis in MAFLD patients. Additionally, the subtypes of DM and lean were associated with an increased risk of atherosclerosis, but a decreased risk of atherosclerosis in the subtype of chronic HBV infection. This population-based study proves the concept that subtypes of MAFLD can help risk stratification of clinical outcomes.