Nonalcoholic Fatty Liver Disease Fibrosis Research Articles

Association Between Noninvasive Liver Fibrosis Scores and Heart Failure in a General Population.

The association between nonalcoholic fatty liver disease and cardiovascular disease is firmly established, yet the association between noninvasive liver fibrosis scores and cardiovascular events remains a topic of uncertainty. Our study aimed to explore the association between liver fibrosis and heart failure. The data set was from the National Health and Nutrition Examination Survey 2011 to 2018. Advanced hepatic fibrosis risk was assessed through 3 noninvasive liver fibrosis scores: Fibrosis-4 score (FIB-4), the nonalcoholic fatty liver disease fibrosis score (NFS), and the aspartate aminotransferase to platelet ratio index (APRI). We included 19 695 eligible participants. The national prevalence of advanced liver fibrosis risk in the United States was 4.20%, 8.06%, and 0.35% as determined by FIB-4, NFS, and APRI scores, respectively. Weighted logistic regression analysis revealed significant associations between advanced liver fibrosis risk and the prevalence of heart failure (continuous variables, FIB-4: odds ratio [OR], 1.15 [95% CI, 1.07-1.23]; NFS: OR, 1.42 [95% CI, 1.23-1.64]; APRI: OR, 1.44 [95% CI, 1.15-1.81]). When the scores were assessed as categorical variables, the results were still significant (FIB-4 ≥2.67 versus FIB-4 <1.3: OR, 2.18 [95% CI, 1.47-3.24]; NFS ≥0.675 versus NFS <-1.455: OR, 2.53 [95% CI, 1.37-4.68]). Subgroup analysis found that the association between APRI and heart failure was stronger in female patients. In the general US population, the prevalence of advanced liver fibrosis risk varied between 0.35% and 8.06% as indicated by noninvasive liver fibrosis scores. FIB-4, NFS, and APRI scores were linked to an elevated prevalence of heart failure.

Burden of liver steatosis and liver fibrosis in a large cohort of people living with HIV.

Liver steatosis (LS) and liver fibrosis (LF) can increase the risk of cardiovascular disease in people with HIV, but their prevalence and associated factors are poorly understood. This study aimed to assess the prevalence of and factors associated with LS and LF in a large cohort of people with HIV. We conducted a cross-sectional study of consecutive people with HIV attending the Clinic of Barcelona from September 2022 to September 2023, excluding those with chronic B or/and C hepatitis virus coinfection. LS was assessed using the Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI), and LF was assessed using the Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS), Fibrosis-4 score (FIB-4), and the European AIDS Clinical Society (EACS) algorithm in both the whole cohort (cohort 1) and in a specific cohort more susceptible to liver disease (cohort 2). We identified independent variables associated with LS and LF using logistic regression. Cohort 1 included 4664 people with HIV; 76% and 37% of them had available HSI and FLI data, LS was present in 28% and 19%, respectively. LF risk was present in 1%, 2%, and 1% of people with HIV according to NFS, FIB-4, and EACS algorithm scores, respectively. Cohort 2 included 1345 people with HIV; 60% and 30% of them had available HSI and FLI data, LS affected 55% and 43% and LF 2%, 5%, or 3%, respectively. Factors associated with LS included current CD4 cell count, diabetes, and hypertension, whereas LF was associated with previous exposure to dideoxynucleoside drugs and current CD4 to LF. Current integrase strand transfer inhibitor (INSTI) therapy appeared protective for LF in cohort 1. In this study, one in four people with HIV had LS, and the prevalence rose to one in two in those with cardiovascular risk factors. The prevalence of LF was low, but it should be considered in older people with HIV with low CD4 counts or high aspartate transaminase levels. A possible protective effect from INSTIs deserves further investigation.

Diagnostic and prognostic value of plasma lipocalin-2 levels in patients with metabolic dysfunction–associated steatotic liver disease

Abstract Background Non-Alcoholic Fatty Liver Disease, recently better recognised as Metabolic Dysfunction–Associated Steatotic Liver Disease, is the most prevalent form of chronic liver disease at present time. It is estimated to impact 32% of the world's population, hence representing a significant health burden. Aim of the work To assess the significance of plasma Lipocalin-2 (LCN2) levels in the diagnosis and prognosis of NAFLD patients. Patients and methods In this retrospective case–control study we recruited 102 subjects aged between 18 and 70 years. The included participants were split into two study groups. Group I: 51 NAFLD patients (61% men, 39% females) and Group II: 51 healthy controls (51% men and 49% females), for whom plasma LCN2 levels were assessed and correlated with NAFLD fibrosis score, FIB4 and fatty liver index. Results In this study, LCN2 levels in NAFLD patients were significantly greater compared to individuals in the control group (p &lt; 0.001), with a mean of 1893.214 ± 1002.852 ng/dL in the cases and a mean of 466.020 ± 397.699 ng/dL in the controls. This suggests the use of LCN2 as a possible diagnostic marker of NAFLD. The mean LCN2 levels in this study also significantly increased as the grade of fatty liver increased from I to III (p &lt; 0.001). This in turn proposes the use of LCN2 as a prognostic marker for NAFLD progression. LCN2 also significantly correlated with the fatty liver index and NAFLD Fibrosis scoring systems, but not with Fib-4. With an area under the ROC of 0.906, it demonstrated excellent diagnostic performance with 84% sensitivity, 90% specificity, 89.6% PPV and 85.2% NPV for the prediction of NAFLD patients. Conclusion Lipocalin-2 performs as a diagnostic and a possible prognostic marker for metabolic dysfunction-associated steatotic liver disease.

A direct comparison of non-invasive blood markers of liver fibrosis as associates of cardiovascular risk. The Athens cardiometabolic registry

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). This risk increases further with advanced liver fibrosis. To date, non-invasive tests (NIT) for liver fibrosis risk have not been established as diagnostic or prognostic biomarkers of CVD. Purpose The purpose of the study was to compare NIT of liver fibrosis with respect to their associations with vascular injury and cardiovascular (CV) events. Methods Individuals without clinically overt CVD and patients with CVD (total n=1,692), consecutively recruited in the Athens Cardiometabolic Registry, were analysed in this study. We retrospectively evaluated the association of NIT (i.e. Fibrosis-4 index (FIB-4), NAFLD Fibrosis score (NFS), BARD score) with indices of subclinical arterial injury (i.e. carotid wall thickness and atherosclerotic plaque for subclinical atherosclerosis, pulse wave velocity (PWV), for arterial stiffness) and the incidence of CV events. Patients were followed-up for CV events for a median time of 39 months. Results Elevated FIB-4 (&amp;gt;2.67) was associated with vascular damage [adjusted odds ratio (aOR)=2.97, 95% confidence intervals (CI)= 1.71-5.78 for maximal wall thickness (maxWT) and aOR=4.58, 95% CI=2.44-8.60 for PWV] across the entire study population, including those with or without clinically overt CVD. NFS&amp;gt; 0.675 showed similar associations but lacked significant correlation with arterial stiffness in coronary artery disease patients. FIB-4&amp;gt; 2.67 and BARD&amp;gt; 2 were associated with increased risk of the composite endpoint of CV death, acute myocardial infarction, or coronary revascularization [adjusted hazard ratio, (aHR)=2.00, 95% CI= 1.12-3.55 and aHR=3.36, 95% CI=1.03-11.0 for FIB-4 (n=842) and BARD (n=887) respectively]. FIB-4 and BARD as continuous variables confered incremental prognostic value compared to European Systematic Coronary Risk Evaluation 2 (SCORE2). Conclusion In a population with a wide range of cardiometabolic risk, FIB-4 was associated with both markers of atherosclerotic disease and arterial stiffness as well as with adverse CV events. These data support further investigation of FIB-4 as a biomarker of CV risk.

Effects of sodium-glucose contrasporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on arterial stiffness, coronary flow reserve and liver steatosis in diabetes

Abstract Background Patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) present an increased risk of cardiovascular disease. Sodium-glucose contrasporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to significantly decrease the risk of cardiovascular complications. Purpose The aim of the study was to investigate the effect of treatment with SGLT-2i or GLP-1RA on cardiovascular function and liver steatosis and fibrosis in patients with T2DM and NAFLD. Methods Forty patients with T2DM and NAFLD (mean age: 58 ± 11 years) were randomized to receive SGLT-2i (dapagliflozin; n = 20) or GLP-1RA (dulaglutide; n = 20). At baseline and after 6 and 12 months of treatment, we measured: (1) perfused boundary region (PBR) of the sublingual microvessels with a diameter 5-25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. (2) Pulse wave velocity (PWV) using Complior (ALAM Medical), (3) coronary flow reserve (CFR) using Doppler echocardiography, (4) LV global longitudinal strain (GLS) using speckle-tracking echocardiography, (5) controlled attenuation parameter (CAP) score to assess steatosis grade and liver stiffness (E) to evaluate fibrosis score using liver elastography (FibroScan, Echosens), and (6) NAFLD fibrosis score (NFS). Results At baseline, patients between the two groups had similar age, sex, HbA1c, steatosis grade, fibrosis score and markers of cardiovascular function (p &amp;gt; 0.05). Compared with baseline, all patients had reduced PBR, PWV, CAP, E and NFS and increased CFR and GLS (p &amp;lt; 0.01) after 12-month treatment. In the whole study population, the percentage reduction of CAP and NFS was correlated with the corresponding decrease of PBR (r = 0.248 and r = 0.387), PWV (r = 0.290 and r = 0.281) and with the increase of GLS (r = -0.320 and r = -0.295) after 12-month treatment (p &amp;lt; 0.05 for all correlations). Both treatments with SGLT-2i and GLP-1RA reduced markers of liver steatosis and fibrosis (Table). Conclusion Both treatments with SGLT-2i and GLP-1RA improve cardiovascular function and reduce liver steatosis in patients with T2DM and NAFLD after 12 months.

DII modulates the relationship between SVD3 and NAFLD prevalence, rather than liver fibrosis severity, in hospitalized T2DM population

Type 2 diabetes (T2DM) patients are at high risk for non-alcoholic fatty liver disease (NAFLD). Studies show SVD3 and dietary inflammatory index (DII) are associated with NAFLD. It’s unknown if they interact in T2DM patients with NAFLD. We collected data from 110 hospitalized T2DM patients, measured physiological and biochemical indicators, conducted dietary surveys, and converted data into DII and NFS, FIB-4, and BARD indices. We used logistic regression, mediation effect analysis, and moderation effect analysis to explore the relationship between DII and SVD3 with NAFLD and liver fibrosis in T2DM patients. DII was not significant in either NAFLD incidence in T2DM patients or liver fibrosis in NAFLD patients. SVD3 was positively correlated with NAFLD incidence in T2DM patients, but this correlation became insignificant as DII increased towards pro-inflammation. SVD3 is positively correlated with NAFLD incidence in T2DM patients, but this correlation becomes less significant as DII increases towards pro-inflammation.

Diagnostic role of the fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score as a noninvasive tool for liver fibrosis scoring.

Nonalcoholic fatty liver disease (NAFLD) is characterized by liver fibrosis, which serves as a crucial indicator of its progression and prognosis. Owing to the limitations of biopsy, which is the gold standard for measuring liver fibrosis, a reliable and noninvasive marker is required. We evaluated the diagnostic role of the fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) in patients with NAFLD with varying severities of liver fibrosis. The FIB-4 index and NFS were calculated using laboratory data from 121 patients who underwent liver biopsies between January 2022 and December 2023. The results were compared with those of the Scheuer scoring system for liver biopsies (F0, F1 + F2, and F3 + F4) to determine the sensitivity and specificity of the FIB-4 index and the liver disease fibrosis score in detecting and staging liver fibrosis. Twenty-one patients had advanced fibrosis (F3-F4), and 100 had minimal or mild fibrosis (F0-F2). The degree of liver fibrosis increased with decreased albumin, alanine aminotransferase and platelet count levels, and increasing age. Receiver operating characteristic curve analysis for the FIB-4 index and NFS revealed that the areas under the curve for the FIB-4 index and NFS were 0.895 (95% confidence interval: 0.836-0.954) and 0.882 (95% confidence interval: 0.813-0.952), respectively. The FIB-4 indices showed 95.24% sensitivity at a cutoff point of 1.30, and 85% specificity at a cutoff point of 2.67, while the NFS indices showed 95.24% sensitivity at -1.455 cutoff point and 95% specificity at a cutoff point of 0.676. The FIB-4 index and NFS may replace biopsy for the detection of fibrosis in patients with NAFLD.

Implementation of machine learning algorithms to screen for advanced liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD): an in-depth explanatory analysis.

Background This study aimed to train machine learning algorithms(MLAs) to detect advanced fibrosis(AF) in MASLD patients at the level of primary care setting and to explain the predictions to ensure responsible use by clinicians. Methods Readily available features of 618 MASLD patients followed up at a tertiary center were used to train five MLAs. AF was defined as liver stiffness≥9.3 kPa, measured via 2-dimension shear wave elastography(n=495) or liver biopsy≥F3(n=123). MLAs were compared to Fibrosis-4 index(FIB-4) and NAFLD fibrosis score(NFS) on 540 MASLD patients from the primary care setting as validation. Feature importance, partial dependence, and shapely additive explanations(SHAP) were utilized for explanation. Results Extreme gradient boosting(XGBoost) achieved an AUC=0.91,outperforming FIB-4(AUC=0.78) and NFS(AUC=0.81, both p&lt;0.05) with specificity=76% vs. 59% and 48% for FIB-4≥1.3 and NFS≥-1.45, respectively(p&lt;0.05). Its sensitivity(91%) was superior to FIB-4(79%). XGBoost confidently excluded AF (negative predictive value=99%) with the highest positive predictive value (31%), superior to FIB-4 and NFS (all p&lt;0.05). The most important features were HbA1c and GGT with a steep increase in AF probability at HbA1c&gt;6.5%. The strongest interaction was between AST and age. XGBoost, but not logistic regression, extracted informative patterns from ALT, LDL-c,and ALP(p&lt;0.001). One quarter of the false positives (FP) were correctly reclassified with only one additional false negative based on the SHAP values of GGT, platelets, and ALT which were found to be associated with a FP classification. Conclusions: An explainable XGBoost algorithm was demonstrated superior to FIB-4 and NFS for screening of AF in MASLD patients at the primary care setting. The algorithm also proved safe for use as clinicians can understand the predictions and flag FP classifications.

Association between Body Fat Distribution and Nonalcoholic Fatty Liver Disease/Fibrosis Based on Race/Ethnicity.

Body fat distribution may impact nonalcoholic fatty liver disease (NAFLD) and significant fibrosis differently according to race/ethnicity. We determined the relationship between body fat distribution and NAFLD/significant fibrosis according to race/ethnicity. A cross-sectional study of 2,395 participants used the National Health and Nutrition Examination Survey 2017 to 2018. NAFLD and significant fibrosis (≥F2) were defined by controlled attenuation parameter scores and liver stiffness measurements on transient elastography, respectively. Visceral and subcutaneous fat volumes were defined by dual-energy X-ray absorptiometry. The odds ratio (OR) for NAFLD per 1-standard deviation in visceral fat volume and subcutaneous fat volume was 2.31 (95% confidence interval [CI], 1.50 to 3.39) and 1.93 (95% CI, 1.43 to 2.61) in total population, respectively. Visceral fat in non-Hispanic Blacks had the highest odds for NAFLD (OR, 2.86; 95% CI, 1.45 to 5.62), and non-Hispanic Whites (OR, 2.29; 95% CI, 1.19 to 4.40) and non-Hispanic Asians (OR, 1.61; 95% CI, 1.13 to 2.29) were in order. Significant associations between subcutaneous fat volume (OR, 2.10; 95% CI, 1.34 to 3.29; P=0.003) or visceral fat volume (OR, 1.35; 95% CI, 1.05 to 1.73; P=0.023) and significant fibrosis were noted among individuals with NAFLD. Hispanics had the highest odds for NAFLD-associated significant fibrosis (OR, 2.74; 95% CI, 1.32 to 5.70), and non-Hispanic Whites (OR, 2.35; 95% CI, 1.11 to 4.98) and non-Hispanic Asians (OR, 2.01; 95% CI, 1.01 to 4.01) were in order. Visceral adiposity was associated with NAFLD and significant fibrosis despite the association of subcutaneous adiposity in NAFLD and significant fibrosis. Racial/ethnic differences in the association between body fat distribution on NAFLD and significant fibrosis were noted.

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

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

Relevance of combined influence of nutritional and inflammatory status on non-alcoholic fatty liver disease and advanced fibrosis: A mediation analysis of lipid biomarkers.

This study aimed to investigate the relationship between advanced lung cancer inflammation index (ALI) and non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis (AF). A total of 5642 individuals from the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020 were examined. Limited cubic spline regression model, and weighted logistic regression were employed to determine if ALI levels were related to the prevalence of NAFLD and AF. Additionally, a mediating analysis was conducted to investigate the role of lipid biomarkers, such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), in the effects of ALI on the prevalence of NAFLD and AF. After adjusting for potential confounders, a significant positive association was found between ALI with NAFLD and AF prevalence. Compared with those in ALI Tertile 1, participants in Tertile 3 had higher odds of NAFLD prevalence (odds ratio [OR]: 3.16; 95% confidence interval [CI]: 2.52-3.97) and AF (OR: 3.17; 95% CI: 2.30-4.36). Participants in both Tertile 2 and Tertile 3 had lower odds of developing AF (P for trend=0.005). Moreover, we discovered a nonlinear association between ALI and NAFLD. An inflection point of 74.25 for NAFLD was identified through a two-segment linear regression model. Moreover, TC and HDL-C levels mediated the association between ALI and NAFLD by 10.2% and 4.2%, respectively (both P<0.001). Our findings suggest that higher ALI levels are positively associated with an increased prevalence of NAFLD and AF, partly mediated by lipid biomarkers.

Association between liver fibrosis and the in-hospital mortality in patients with sepsis-induced coagulopathy

BackgroundThe impact of liver fibrosis on the clinical outcomes of patients with sepsis-induced coagulopathy (SIC) is not well understood. This study aimed to evaluate the association between liver fibrosis scores and in-hospital mortality in SIC patients.MethodsIn this retrospective observational cohort study, data were collected from patients diagnosed with sepsis and admitted to the ICU at the First Affiliated Hospital of Wenzhou Medical University between January 2017 and December 2023. Liver fibrosis was evaluated using three scores: Fibrosis-4 (Fib-4), Aspartate Aminotransferase–to–Platelet Ratio Index (APRI), and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Patients were divided into tertiles according to their liver fibrosis scores, and the primary outcome was in-hospital mortality. Multivariable logistic regression and restricted cubic spline regression analyses were used to assess associations, complemented by sensitivity analyses through subgroup evaluations.ResultsThe cohort included 948 patients diagnosed with SIC with an in-hospital mortality of 26.16%. Multivariate logistic regression analysis revealed a significant association between higher liver fibrosis scores and increased in-hospital mortality. Specifically, patients in the highest tertile of Fib-4, APRI, and NFS scores had significantly higher odds of mortality (FIB-4: OR 3.62, 95% CI 1.03–12.69; APRI: OR 2.16, 95% CI 0.88–5.30; NFS: OR 6.80, 95% CI 2.11–21.93) compared to those in the lowest tertile. The restricted cubic spline regression model showed a linear increase in the risk of in-hospital mortality with increasing liver fibrosis score. Sensitivity analysis confirmed the consistency and stability of the results across the different subgroups.ConclusionOur study suggests that elevated liver fibrosis scores, particularly Fib-4 and NFS, are associated with higher in-hospital mortality in SIC patients. Further research, especially larger prospective studies, are needed to validate these findings.

The effect of probiotic supplementation on non-alcoholic fatty liver disease (NAFLD) fibrosis score in patients attending a tertiary hospital clinic in Cairo, Egypt.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation (> 5% of liver tissue) in the absence of alcohol abuse or other chronic liver diseases. NAFLD can progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This study aimed to assess the efficacy of probiotic (lactobacillus) supplementation on NAFLD fibrosis score. A double-arm randomized controlled trial was conducted in the family medicine clinic of a tertiary hospital, enrolling patients with sonographic evidence of NAFLD. Fifty patients were divided into two groups: the Probiotic group received lifestyle modification instructions along with daily probiotic supplementation for twelve weeks, with regular monthly follow-up visits. The Standard Treatment group received low-fat diet and lifestyle modification instructions only. The mean age of participants was 46.10 years (SD 10.11), with 70% females and 30% males. The study found a statistically significant difference in liver enzymes (ALT and AST) and BMI in the probiotic group before and after intervention. However, there was no significant difference in NAFLD fibrosis score between the two groups. Short-term probiotic treatment resulted in improvements in ALT, AST, and BMI in the probiotic group, but did not significantly affect NAFLD fibrosis score. Further research with larger sample sizes and longer follow-up periods is warranted. The clinical trial was registered at Protocol Registration and Results System with number NCT06074094 (12/09/2021).

Determinants of advanced non-alcoholic fatty liver disease fibrosis in the obese population

Determinants of advanced non-alcoholic fatty liver disease fibrosis in the obese population

Overlapping group between non-alcoholic fatty liver disease and metabolic associated fatty liver disease better for liver research.

Metabolic associated fatty liver disease (MAFLD) was proposed to replace "non-alcoholic fatty liver disease (NAFLD) with new diagnostic criteria." The group meeting these two diagnostic criteria is called "Overlapping Fatty Liver Disease (FLD)." Its clinical characteristics remain unknown. This study included participants from the Taiwan Bio-Bank database, where NAFLD was defined as hepatic steatosis in liver ultrasound, with exclusion of other known chronic liver diseases. MAFLD was defined as the presence of hepatic steatosis plus metabolic dysfunction, defined as having any of following three criteria: overweight/obesity, type 2 diabetes mellitus (DM), or ≥2 metabolic risk abnormalities in lean/normal weight subjects. According to these two diagnostic criteria, three groups were identified: "overlapping FLD", "NAFLD alone", and "MAFLD alone." NAFLD fibrosis score (NFS) >0.675 was defined as advanced liver fibrosis. Eight thousand thirty-eight NAFLD participants (age 55.86 ± 10.12; males 41.07%) were included in the final analysis. Of them, "overlapping FLD" was diagnosed in 7377 (91.8%) and "NAFLD alone" in 661 (8.2%) participants. "Overlapping FLD" patients were older and had a higher percentage of male, worse metabolic profiles, higher NFS, and the percentage of carotid plaques was higher than those with "NAFLD alone." Multivariate analysis showed age, hypertension, DM, and BMI were positively associated with advanced liver fibrosis in "overlapping FLD" patients. "Overlapping FLD" is better for liver research due to identifying a high-risk population among NAFLD patients. NAFLD definition introduces the heterogeneity through "NAFLD alone" group and MAFLD criteria overcome this limitation.

Elevated Concurrent Carotid Atherosclerosis Rates in Patients with metabolic dysfunction-associated fatty liver disease (MAFLD) Compared to non-alcoholic fatty liver disease (NAFLD): A Cross-sectional Observational Study

Background and AimNon-alcoholic fatty liver disease (NAFLD) has been recognized as an independent risk factor for atherosclerotic cardiovascular disease. Recently, there has been a shift towards diagnosing metabolic dysfunction-associated fatty liver disease (MAFLD), offering simplified criteria and improved risk assessment. However, the association between MAFLD and carotid atherosclerosis remains poorly understood. Methods and ResultsThe study analyzed the association of concurrent carotid atherosclerosis between NAFLD and MAFLD patients with a retrospective cohort design. The study enrolled participants who underwent abdominal and carotid artery ultrasounds from a medical center in Taiwan. NAFLD and MAFLD were diagnosed based on imaging and specific criteria. Associations between NAFLD, MAFLD, and carotid atherosclerosis were analyzed using logistic regression.Among 11,194 participants, 57.1% were diagnosed with fatty liver disease, among which the NAFLD-MAFLD group comprised 4,689 individuals, with 900 in the NAFLD-only group and 669 in the MAFLD-only group. Significant demographic and clinical differences were observed between groups. Logistic regression showed that the MAFLD-NAFLD group and MAFLD-only group had significantly higher odds of concomitant carotid atherosclerosis. Among MAFLD patients, 65.5% had concurrent carotid arteriosclerosis with an odds ratio of 2.35 compared to non-MAFLD patients. The odds ratios for variables in MAFLD patients, such as diabetes mellitus, Fibrosis-4(FIB-4), number of FIB-4 > 1.3, and number of NAFLD fibrosis score > -1.455 were all greater than 2. ConclusionsMAFLD is associated with a higher prevalence of carotid atherosclerosis, compared to NAFLD. This suggests that MAFLD may serve as a significant risk factor for cardiovascular complications.

FLI and FIB-4 in diagnosing metabolic dysfunction-associated steatotic liver disease in primary care: High prevalence and risk of significant disease

Introduction and ObjectivesPublic health policies in metabolic dysfunction-associated steatotic liver disease (MASLD) are still lacking. This study aims to estimate the prevalence and severity of MASLD in primary health care (PHC) through non-invasive markers. Patients and MethodsTwo-phase study, including a retrospective (RETR) and a prospective (PROS) one, was carried out in PHC in Brazil. In RETR, metabolic and hepatic profiles of 12,054 patients, including FIB-4, were evaluated. In PROS, 350 patients were randomly selected and submitted to a clinical and nutritional assessment. ResultsRETR (65.4 % women, mean age 55.3 years old): dyslipidemia, hypertension, and type 2 diabetes mellitus (T2DM) present in 40.8 %, 34.3 %, and 12.2 % of the electronic health records, respectively. Fasting glucose >100 mg/dL in 34.5 %, and glycated hemoglobin higher than 5.7 % in 51.5 %, total cholesterol >200 mg/dL and triglycerides >150 mg/dL in 40.8 % and 32.1 %, respectively. Median FIB-4 was of 1.33, 5 % >2.67. No one had MASLD as a diagnostic hypothesis; PROS(71.8 % women, mean age 58 years old): body mass index (BMI) ≥30 kg/m² in 31.8 %. MASLD prevalence (FLI≥ 30 + cardiometabolic features) of 62.1 %; 39.4 % of patients had FLI ≥60, with higher BMI, waist circumference, fasting glucose, triglycerides, AST, ALT and GGT, as well as lower HDL-cholesterol (p < 0.001). FIB-4>1.3 in 40 % and NAFLD Fibrosis Score (NFS)>-1.45 in 59.2 % of steatotic patients. ConclusionsThere is a high prevalence of MASLD in PHC, with a significant risk of liver fibrosis. These findings reinforce we need to develop public policies to defeat MASLD epidemics.

A metabolome-derived score predicts metabolic dysfunction-associated steatohepatitis and mortality from liver disease

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related mortality. However, biomarkers predicting both MASH and mortality are missing. We developed a metabolome-derived prediction score for MASH and examined whether it predicts mortality in Chinese and European cohorts. MethodsThe MASH prediction score was developed using a multi-step machine learning strategy, based on 44 clinical parameters and 250 plasma metabolites measured by proton nuclear magnetic resonance (1H-NMR) in 311 Chinese adults undergoing a liver biopsy. External validation was conducted in a Finnish liver biopsy cohort (n=305). We investigated association of the score with all-cause and cause-specific mortality in the population-based Shanghai Changfeng Study (n=5,893) and the UK Biobank (n=111,673). ResultsA total of 24 clinical parameters and 194 1H-NMR metabolites were significantly associated with MASH in the Chinese liver biopsy cohort. The final MASH score included body mass index, aspartate transaminase, tyrosine, and the phospholipids-to-total lipids ratio in very-low density lipoprotein. The score identified patients with MASH with AUROCs of 0.87 (95% CI, 0.83-0.91) and 0.81 (95% CI, 0.75-0.87) in the Chinese and Finnish cohorts, with high negative predictive values. Participants with a high or intermediate risk of MASH based on the score had a markedly higher risk of MASLD-related mortality than those with a low risk in Chinese (HR, 23.19; 95%CI, 4.80-111.97) and European individuals (HR, 27.80; 95%CI, 15.08-51.26) after 7.4 and 12.6 years of follow-up. The MASH prediction score was superior to the FIB-4 index and the NAFLD Fibrosis Score in predicting MASLD-related mortality. ConclusionThe metabolome-derived MASH prediction score accurately predicts risk of MASH and MASLD-related mortality in both Chinese and European individuals. Impact and implicationsMetabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related death. However, biomarkers predicting not only MASH, but also death due to liver disease, are missing. We established a MASH prediction score based on 44 clinical parameters and 250 plasma metabolites using a machine learning strategy. This metabolome-derived MASH prediction score could accurately identify patients with MASH among both Chinese and Finnish individuals, and it was superior to the FIB-4 index and the NAFLD Fibrosis Score in predicting MASLD-related death in the general population. Thus, the new MASH prediction score is a useful tool for identifying individuals with a markedly increased risk of serious liver-related outcomes among at-risk and general populations.

The Relationship Between Liver Fibrosis Scores and Ascending Aortic Dilatation.

Non-alcoholic fatty liver disease (NAFLD) is related to an increased atherosclerotic cardiovascular disease (ASCVD) risk. This study investigated a potential relationship between liver fibrosis scores (LFS) reflecting NAFLD and ascending aortic dilatation (AAD). This is an observational and cross-sectional study. Patients were consecutively enrolled from a cardiology clinic. The NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) index, aspartate aminotransferase (AST) to platelet ratio (APRI), and BARD scores of each patient were calculated. The ascending aortic diameters were evaluated by transthoracic echocardiography according to current clinical guidelines. The patients were allocated into two groups with and without AAD. A total of 272 patients were included in the study. In AAD group, age, patients with hypertension (HT), coronary artery disease (CAD), FIB-4 index, BARD score and the NFS were significantly higher. As compared to the AAD group, body mass index (BMI), hemoglobin, and diuretic use were significantly higher in patients without aortic dilatation. The NFS with AAD, and NFS and FIB-4 index with indexed aortic diameter (AI) showed significant positive correlation (R=0.546, R=0.332, R=0.314 with p<0.001, respectively). In multivariate logistic regression analysis hemoglobin levels (OR=0.728, 95%CI: 0.553-0.958; p=0.023), BMI (OR=0.762, 95%CI: 0.668-0.869, p<0.001), HT (OR=3.269, 95%CI: 1.045-10.220; p=0.042), BARD score (OR=1.248, 95%CIL 0.815-1.955; p=0.044), and FIB-4 index (OR=2.432, 95%CI: 1.395-4.246; p=0.002) were found to be independently related to AAD. Our study demonstrated a statistically significant relationship between NFS, FIB-4 index, BARD score and AAD. The presence of positive correlation among LFS and AAD in our study is remarkable. This may emphasize the increased risk of AAD in NAFLD.

Metabolic dysfunction-associated steatotic liver disease and gallbladder polyp development: an observational study

The influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on gallbladder polyp development in both sexes remains elusive. Therefore, to clarify the role of MASLD in gallbladder polyp development, we investigated the longitudinal association between MASLD and gallbladder polyps. In this observational study, we included 5,527 gallbladder polyp-free patients who underwent > 2 health check-ups over > 2 years. Generalized estimation equations were used to analyze associations between MASLD and gallbladder polyp development according to repeated measures at baseline and the most recent stage. Gallbladder polyp development rates in men and women were 7.5% and 5.6% (p < 0.01), respectively. MASLD was not significantly correlated with gallbladder polyp development. Regarding the association between gallbladder polyp development (men: ≥6 mm and women: ≥5 mm) and the number of MASLD components following lifestyle habits, men and women with ≥ 4 MASLD components had odds ratios of 3.397 (95% confidence interval: 1.096–10.53) and 5.338 (1.054–27.04), respectively. Higher nonalcoholic fatty liver disease fibrosis scores were associated with significant risk of gallbladder polyp development in women (1.991, 1.047–3.785). Although MASLD influence on gallbladder polyp development differs by sex, close monitoring of patients with an increasing number of MASLD components is essential to prevent gallbladder polyp development. Specifically, men with ≥ 4 MASLD components should be monitored for gallbladder polyps measuring ≥ 6 mm.