Fatty Liver Disease Fibrosis Score Research Articles

Factors Associated with Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

Introduction. Nonalcoholic fatty liver disease includes conditions such as nonalcoholic steatosis and nonalcoholic steatohepatitis, with varying degrees of fibrosis that can progress to cirrhosis and hepatocellular carcinoma. Although the gold standard for its diagnosis remains liver biopsy, many non-invasive methods have been proposed to aid in both the diagnosis of the disease and the evaluation of the presence of liver fibrosis, which is a strong and independent factor for liver related mortality. Objectives. The objectives of this study were: 1) to identify the clinical and laboratory features associated with the presence of advanced fibrosis in individuals with biopsy-confirmed nonalcoholic fatty liver disease; 2) to evaluate the performance of non-invasive markers in identifying patients with advanced fibrosis. Methods. A cross-sectional-analytic study that evaluated patients with nonalcoholic fatty liver disease treated in the outpatient clinic of a university hospital of reference in hepatology, between January 2013 and December 2016. Results. 81 patients aged 53.3 ± 9.8 years were included in this study; 39.5% were men and 70.1% were obese. When comparing patients with advanced fibrosis to those without advanced fibrosis, patients with advanced fibrosis had a lower proportion of males than females (17.6 vs. 45.4%, p = 0.038), a higher proportion of hypothyroidism (29.4 vs. 6.3%, p = 0.017) and a higher median AST (52 vs. 31 U/L, p = 0.005). In logistic regression analysis, only hypothyroidism was independently associated with advanced fibrosis (OR = 4.975; CI 95% 1.050 - 23.574; p = 0.043). Spearman correlation analysis showed that higher levels of fibrosis on liver biopsy, were associated with higher levels of TSH (r = 0.304; p = 0.036), AST (r = 0.277; p = 0.019), GGT (r = 0.284; p = 0.017) and LDL (r = 0.258; p = 0.037). Regarding the performance of the non-invasive markers, the area under the ROC curve of Fibrosis 4 score was 0.723 (p = 0.008), that of Nonalcoholic fatty liver disease fibrosis score was 0.713 (p = 0.022), that of gamma-glutamyl transferase platelet ratio was 0.697 (p = 0.019) and that of aspartate-to-alanine aminotransferase ratio was 0.689 (p = 0.031). Conclusions. Hypothyroidism is a factor independently associated with advanced fibrosis. In the outpatient setting, non-invasive markers may be useful in identifying patients with advanced fibrosis.

Effect of Exenatide on Nonalcoholic Steatohepatitis and Inflammation-Related Indices in Diabetic Patients with Non-Alcoholic Fatty Liver Disease.

Purpose: Diabetes mellitus is a chronic disease often associated with nonalcoholic steatohepatitis (NASH) and obesity. Both obesity and NASH are closely related to inflammation. In this study, we examined how exenatide, a glucagon-like peptide 1 analog, affects inflammatory and NASH-related markers in patients with diabetes. Methods: This retrospective study was conducted on 100 patients who visited our hospital with a diagnosis of type 2 diabetes mellitus. NASH-related indices and inflammatory indices were calculated from data obtained at baseline and at the third month of exenatide treatment. All data were analyzed first in all patients, and then the patients were grouped according to glycosylated hemoglobin A1c (HbA1c) levels of <8% or ≥8% and body mass index (BMI) of <40 or ≥40 kg/m2 and their data were reanalyzed. Results: A highly significant improvement was found in the conventional lipid profile. Among NASH-related indices, the nonalcoholic fatty liver disease (NAFLD) fibrosis score and aspartate aminotransferase-platelet ratio index (APRI) showed statistically significant decreases (P < 0.001 and P = 0.016, respectively). In particular, these significant decreases were independent of BMI and glycemic parameters. No statistically significant change was found in inflammatory indices. The decreases in NAFLD fibrosis score and APRI were statistically more significant in the group with HbA1c ≥8% (P = 0.021 and P = 0.002, respectively) and the group with BMI ≥40 kg/m2 (P = 0.002 and P = 0.029, respectively). Conclusions: Besides its established effects, such as lowering fasting plasma glucose levels and weight loss, exenatide exerts positive effects on the conventional lipid profile and NASH-associated indexes.

Comparison of liver fibrosis scores for predicting mortality and morbidity in heart failure with preserved ejection fraction.

Liver fibrosis scores (LFSs) are non-invasive and effective tools for estimating cardiovascular risks. To better understand the advantages and limitations of currently available LFSs, we determined to compare the predictive values of LFSs in heart failure with preserved ejection fraction (HFpEF) for primary composite outcome, atrial fibrillation (AF), and other clinical outcomes. This was a secondary analysis of the TOPCAT trial, and 3212 HFpEF patients were enrolled. Five LFSs, namely, non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 score (FIB-4), BARD, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and Health Utilities Index (HUI) scores were adopted. Cox proportional hazard model and competing risk regression model were performed to assess the associations between LFSs and outcomes. The discriminatory power of each LFS was evaluated by calculating the area under the curves (AUCs). During a median follow-up of 3.3years, a 1-point increase in the NFS [hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.04-1.17], BARD (HR 1.19; 95% CI 1.10-1.30), and HUI (HR 1.44; 95% CI 1.09-1.89) scores was associated with an increased risk of primary outcome. Patients with high levels of NFS (HR 1.63; 95% CI 1.26-2.13), BARD (HR 1.64; 95% CI 1.25-2.15), AST/ALT ratio (HR 1.30; 95% CI 1.05-1.60), and HUI (HR 1.25; 95% CI 1.02-1.53) were at an increased risk of primary outcome. Subjects who developed AF were more likely to have high NFS (HR 2.21; 95% CI 1.13-4.32). High levels of NFS and HUI scores were a significant predictor of any hospitalization and hospitalization for heart failure. The AUCs for the NFS in predicting primary outcome (0.672; 95% CI 0.642-0.702) and incident of AF (0.678; 95% CI 0.622-0.734) were higher than other LFSs. In light of these findings, NFS appears to have superior predictive and prognostic utility compared with AST/ALT ratio, FIB-4, BARD, and HUI scores. (https://clinicaltrials.gov). Unique identifier: NCT00094302.

Association between daidzein intake and metabolic associated fatty liver disease: A cross-sectional study from NHANES 2017-2018.

Metabolic associated fatty liver disease (MAFLD) has become the most common liver disease globally, yet no new drugs have been approved for clinical treatment. Therefore, we investigated the relationship between dietary intake of soy-derived daidzein and MAFLD, to find potentially effective treatments. We conducted a cross-sectional study using data from 1,476 participants in National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018 and their associated daidzein intake from the flavonoid database in the USDA Food and Nutrient Database for Dietary Studies (FNDDS). We investigated the relationship between MAFLD status, controlled attenuation parameter (CAP), AST/Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4), liver stiffness measurement (LSM), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), hepatic steatosis index (HSI), fatty liver index (FLI), and daidzein intake by adjusting for confounding variables using binary logistic regression models and linear regression models. In the multivariable-adjusted model II, there was a negative association between daidzein intake and the incidence of MAFLD (OR for Q4 versus Q1 was 0.65, 95% confidence interval [CI] = 0.46-0.91, p = 0.0114, p for trend was 0.0190). CAP was also negatively associated with daidzein intake, β = -0.37, 95% CI: -0.63 to -0.12, p = 0.0046 in model II after adjusting for age, sex, race, marital status, education level, family income-to-poverty ratio (PIR), smoking, and alcohol consumption. Stratified by quartiles of daidzein intake, trend analysis of the relationship between daidzein intake and CAP remained significant (p for trend = 0.0054). In addition, we also found that HSI, FLI, and NFS were negatively correlated with daidzein intake. LSM was negatively related to daidzein intake but had no statistical significance. The correlation between APRI, FIB-4, and daidzein intake was not strong (although p < 0.05, β values were all 0). We found that MAFLD prevalence, CAP, HSI, and FLI, all decreased with increased daidzein intake, suggesting that daidzein intake may improve hepatic steatosis. Therefore, dietary patterns of soy food or supplement consumption may be a valuable strategy to reduce the disease burden and the prevalence of MAFLD.

Association between Cardiovascular Disease and Liver Disease, from a Clinically Pragmatic Perspective as a Cardiologist.

Cardiovascular diseases and liver diseases are closely related. Non-alcoholic fatty liver disease has the same risk factors as those for atherosclerotic cardiovascular disease and may also be a risk factor for atherosclerotic cardiovascular disease on its own. Heart failure causes liver fibrosis, and liver fibrosis results in worsened cardiac preload and congestion. Although some previous reports regard the association between cardiovascular diseases and liver disease, the management strategy for liver disease in patients with cardiovascular diseases is not still established. This review summarized the association between cardiovascular diseases and liver disease. In patients with non-alcoholic fatty liver disease, the degree of liver fibrosis progresses with worsening cardiovascular prognosis. In patients with heart failure, liver fibrosis could be a prognostic marker. Liver stiffness assessed with shear wave elastography, the fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score is associated with both liver fibrosis in patients with liver diseases and worse prognosis in patients with heart failure. With the current population ageing, the importance of management for cardiovascular diseases and liver disease has been increasing. However, whether management and interventions for liver disease improve the prognosis of cardiovascular diseases has not been fully understood. Future investigations are needed.

Prognostic value of non-alcoholic fatty liver disease fibrosis score in patients undergoing cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an effective option in the treatment of patients with heart failure and wide QRS. Non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been shown to predict cardiac events in several patient populations. However, the relationship between NFS and response to CRT has not been investigated. The aim of the study was to investigate the predictive role of NFS in the assessment of response after CRT. Three hundred thirty-six patients with heart failure undergoing CRT were prospectively studied. Liver fibrosis were assessed according to the non-alcoholic fatty liver disease fibrosis score (NFS), which includes age, body mass index, impaired fasting glycemia or diabetes mellitus, aspartate aminotransferase /alanine aminotransferase ratio, platelets, and albumin. Echocardiographic response to CRT was defined by a ≥15% reduction in left ventricular end-systolic volume at six months at follow-up. Two hundred thirty-eight patients (71%) had CRT response after 6 months of follow-up. Receiver-operator characteristic curve analysis showed NFS cutoff value of<-1.12 for predicting CRT response with a sensitivity of 70.4% and a specificity of 52.9%. The patients were also divided into four groups according to the quartiles of NFS. The proportion of response to CRT was increased with lower level of NFS value. Multivariate logistic regression analysis demonstrated the NFS score<-1.12 and LVIDs were independent predictors of the CRT response. In the second model of analysis which included NFS, quartiles demonstrated that fourth NFS quartile and LVIDs were independent predictors of CRT response. Liver fibrosis assessed by NFS can provide valuable information to predict reverse remodeling in patients undergoing CRT. The present study supports monitoring of NFS to improve preoperative risk stratification of these patients.

Low thyroid function is associated with an increased risk of advanced fibrosis in patients with metabolic dysfunction-associated fatty liver disease

AimsObservational studies showed that low thyroid function may perturb liver function. We aimed to evaluate the association of low thyroid function with both metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced hepatic fibrosis.MethodsParticipants who underwent abdominal ultrasonography and thyroid function test in a Chinese hospital from 2015 to 2021were enrolled. Fibrosis-4 index (FIB-4) > 2.67 and/or non-alcoholic fatty liver disease fibrosis score (NFS) > 0.676 were used to define advanced fibrosis. Descriptive analyses were performed to characterize the epidemiology of MAFLD according to levels of thyroid-stimulating hormone (TSH). The logistic regression model was applied to estimate the association of low thyroid function with MAFLD and advanced fibrosis.ResultsA total of 19,946 participants (52.78% males, mean age: 47.31 years, 27.55% MAFLD) were included, among which 14,789 were strict-normal thyroid function, 4,328 were low-normal thyroid function, 829 were subclinical hypothyroidism. TSH levels were significantly higher in MAFLD patients with a FIB-4 > 2.67 and /or NFS > 0.676 than their counterparts. The logistic regression model adjusted for age and sex showed that low-normal thyroid function increased the risk of MAFLD (odds ratio [OR] = 1.09; 95% confidence interval [CI] 1.01–1.18). Multivariable regression model adjusted for age, sex, body mass index, type 2 diabetes, and hypertension showed low-normal thyroid function increased the risk of advanced fibrosis in patients with MAFLD (FIB-4 > 2.67: OR = 1.41, 95% CI 1.02–1.93; NFS > 0.676: OR = 1.72, 95% CI 1.08–2.72).ConclusionElevated TSH concentrations are associated with advanced hepatic fibrosis, even in the euthyroid state.

Serum biomarkers of liver fibrosis identify globus pallidus vulnerability

The CNS manifestation of chronic liver disease can include magnetic resonance (MR) signal hyperintensities in basal ganglia structures. Here, relations between liver (serum-derived fibrosis scores) and brain (regional T1-weighted signal intensities and volumes) integrity were evaluated in a sample of 457 individuals including those with alcohol use disorders (AUD), people living with human immunodeficiency virus (HIV), those comorbid for AUD and HIV, and healthy controls. Liver fibrosis was identified from cutoff scores as follows: aspartate aminotransferase to platelet ratio index (APRI) > 0.7 in 9.4% (n = 43) of the cohort; fibrosis score (FIB4) > 1.5 in 28.0% (n = 128) of the cohort; and non-alcoholic fatty liver disease fibrosis score (NFS) > -1.4 in 30.2% (n = 138) of the cohort. Presence of serum-derived liver fibrosis was associated with high signal intensities selective to basal ganglia (i.e., caudate, putamen, and pallidum) structures. High signal intensities in the pallidum, however, explained a significant portion of the variance in APRI (25.0%) and FIB4 (23.6%) cutoff scores. Further, among the regions evaluated, only the globus pallidus showed a correlation between greater signal intensity and smaller volume (r = -0.44, p <.0001). Finally, higher pallidal signal intensity correlated worse ataxia (eyes open ρ = -0.23, p =.0002; eyes closed ρ = -0.21, p =.0005). This study suggests that clinically relevant serum biomarkers of liver fibrosis such as the APRI may identify individuals vulnerable to globus pallidus pathology and contribute to problems with postural balance.

Differential Effects of COVID-19 Hospitalization on the Trajectory of Liver Disease Progression.

Patients with chronic liver disease (CLD) were significantly affected by COVID-19. Despite evidence of acute hepatic injury and increased mortality, the long-term effects of COVID-19 hospitalization on the natural history of CLD patients are unknown. The Massachusetts General Hospital COVID-19 registry was used to obtain a cohort of CLD patients hospitalized between March 8 and June 3, 2020. The Partners Research Patient Data Registry was used to develop a matched CLD patient control list without COVID-19. Fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS), and model for end-stage liver disease/Na (MELD-Na) scores were calculated pre-, day of, and 1-year post-discharge from admission. Unpaired t-test was used to compare continuous variables. Fifty-two COVID-19 patients and 92 control patients with CLD were included. Patients with non-cirrhotic CLD who were hospitalized for COVID-19 had an acute rise in FIB-4 on admission with subsequent improvement on one-year follow-up demonstrating no difference in progression of liver disease compared to the controls (P= .87, confidence interval [CI]-0.088 to 0.048). Similar trends were observed in nonalcoholic fatty liver disease patients using NFS (P= .48, CI-0.016 to 0.023). In contrast, patients with cirrhosis experienced rise in MELD-Na postadmission compared to the control cirrhosis group (0.35 vs-0.076/month; P= .04, CI-0.827 to-0.025), suggesting a potential for long-term consequences of COVID-19. Non-cirrhotic CLD patients who survive COVID-19 hospitalization do not appear to have change in FIB-4, NFS scores at one year. However, patients with cirrhosis exhibit increasing MELD-Na one-year post-COVID suggesting a differential effect of acute COVID-19 on the trajectory of established cirrhosis.

Association between liver fibrosis and thrombotic or bleeding events in acute coronary syndrome patients

BackgroundThe prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome.MethodsWe included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS).ResultsDuring the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups.ConclusionsIn ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.

Blood pressure stratification for predicting liver fibrosis risk in metabolic dysfunction associated fatty liver disease

Introduction and ObjectivesThe optimal blood pressure (BP) range for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is currently unknown. This study aimed to explore the relationship between stratified BP levels and MAFLD progression. Patients and MethodsThe data of adults who underwent yearly health check-ups were screened to establish both a cross-sectional and a 6-year longitudinal cohort of individuals with MAFLD. BP was classified into the following categories optimal, normal, high-normal, and hypertension. Liver fibrosis was diagnosed with fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). ResultsA total of 10,232 individuals were included in the cross-sectional cohort. In the MAFLD population, individuals with liver fibrosis had significantly higher BP levels and hypertension prevalence (P < 0.001) than those without. Furthermore, liver fibrosis score was significantly associated with BP levels (P < 0.001). In the 6-year longitudinal cohort of 3661 individuals with MAFLD without liver fibrosis, the incidence rates of liver fibrosis increased with increasing BP levels as follows optimal=11.20%, normal=13.90%, high-normal=19.50%, hypertension=26.20% (log-rank 22.205; P < 0.001). Cox regression analysis showed that both baseline high-normal BP (hazard ratio [HR], 1.820; P=0.019) and hypertension (HR, 2.656; P < 0.001) were predictive of liver fibrosis. ConclusionsBP stratification may be useful in predicting the progression of MAFLD. Individuals having MAFLD with concurrent hypertension or high-normal BP are at a higher risk of liver fibrosis. These findings may provide a criteria for early intervention of MAFLD to prevent liver fibrosis.

Association of liver fibrosis biomarkers with overall and CVD mortality in the Korean population: The Dong-gu study.

This study evaluated the associations of liver fibrosis biomarkers [non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4), aspartate aminotransferase/platelet ratio index (APRI), and BARD score] with mortality in Korean adults aged ≥50 years. We analyzed 7,702 subjects who participated in Dong-gu Study. The associations of liber fibrosis biomarkers with mortality were investigated using Cox proportional hazards models. Overall mortality increased with increasing NFS level [adjusted hazard ratio (aHR) 4.3, 95% confidence interval (CI) 3.3-5.5 for high risk vs. low risk], increasing FIB-4 level (aHR 3.5, 95% CI 2.9-4.4 for high risk vs. low risk), and increasing APRI level (aHR 3.5, 95% CI 2.1-5.8 for high risk vs. low risk) but not with BARD score. The Harrell's concordance index for overall mortality for the NFS and FIB-4 was greater than that for the APRI and BARD score. In conclusion, NFS, FIB-4, and APRI showed a significant relationship with the overall mortality, and NFS and FIB-4 showed a significant relationship with the CVD mortality after adjustment for covariates. In addition, the NFS and FIB-4 were more predictive of overall mortality than the APRI and BARD score in Korean adults aged ≥50 years.

Association of metabolic dysfunction-associated fatty liver disease with chronic kidney disease: a Chinese population-based study

Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a multisystem disorder, but its relationship with kidney injury remains controversial. This study aimed to evaluate MAFLD effects on the chronic kidney disease (CKD) prevalence in a general population in China. Methods In total, 15,010 individuals from the Health Management Center of West China Hospital from July 2020 to June 2021 were screened. Hepatic steatosis was defined as a median FibroScan controlled attenuation parameter (CAP)≥240 dB/m using liver ultrasound transient elastography. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or the presence of albuminuria. The association of MAFLD with CKD was examined using logistic regression. Risk factors for CKD in different MAFLD subgroups were also investigated. Results A total of 8226 individuals were finally included. Of them, 4406 (53.6%) had MAFLD, and 592 (7.2%) had CKD. After propensity score matching (PSM), 5530 eligible subjects were selected (n = 2765 in each group). There was a higher CKD prevalence in subjects with MAFLD than in those without MAFLD (8.9% vs. 5.4%, p < 0.001). MAFLD was significantly associated with a higher CKD prevalence (OR 1.715, 95% CI 1.389–2.117, p < 0.001), although it was not an independent risk factor. The results indicated that age, diabetes mellitus (DM), overweight/obesity, hypertension, hyperuricemia, hypertriglyceridemia, remnant cholesterol (RC), and C-reactive protein (CRP) were independently associated with a higher CKD prevalence. In the subgroup analysis, hypertension, hyperuricemia, RC, and the nonalcoholic fatty liver disease fibrosis score (NFS) were independent risk factors for the prevalence of CKD in individuals with DM or prediabetes and MAFLD. Furthermore, hypertension, hyperuricemia, and body fat percentage (BFP) were independently associated with CKD in subjects with MAFLD without DM. Conclusion Individuals with MAFLD had a higher prevalence of CKD, whereas it was not an independent risk factor for CKD.

Reappraisal of fibrosis-4 index and non-alcoholic fatty liver disease fibrosis score for advanced fibrosis in average-risk population.

The current cut-offs for fibrosis-4 (FIB-4) and non-alcoholic fatty liver disease fibrosis score (NFS) are suboptimal for screening because of low accuracy and high false-negative rates in average-risk populations. This study aimed to reappraisal the performance of FIB-4 and NFS in such average-risk populations. This is a cross-sectional study, which retrospectively reviewed the magnetic resonance elastography (MRE) data of 8,522 subjects. Individuals with history of significant alcohol consumption and those with positive viral serologic markers were excluded. Finally, 6,215 average-risk individuals were analyzed. The area under the receiver operating characteristic curves (AUROCs) of FIB-4 for the diagnosis of advanced hepatic fibrosis was higher than that in the NFS especially in the metabolically healthy. The AUROCs of FIB-4 for in the average-risk population was also higher than that in the NFS (0.840 in FIB-4 vs. 0.798, P = 0.036). However, the sensitivity of FIB-4 and NFS was low (69.6 and 61.4%, respectively) in applying the current cut-off of FIB-4 [1.3 (2.0)] and NFS [-1.455 (0.12)]. At cut-off of FIB-4 at 1.0, sensitivity (90.2%), and negative predictive value (99.7%) were improved. The diagnostic performance of FIB-4 was better than that of NFS for screening hepatic fibrosis in average-risk populations. It is recommended to use FIB-4 rather than NFS, when screening for hepatic fibrosis in general population.

Diagnostic Performance of Noninvasive Tests for Advanced Hepatic Fibrosis in Young Age Population

Most noninvasive tests (NITs) for hepatic fibrosis are designed for middle-aged patients with chronic liver disease. We compared the diagnostic performance of major NITs (aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 index, and nonalcoholic fatty liver disease fibrosis score) for a community-based cohort. This cross-sectional study analyzed 8775 participants who underwent magnetic resonance elastography at community health check-up centers. Advanced hepatic fibrosis (≥F3)was defined by magnetic resonance elastography thresholds of 3.6 kPa. Thediagnostic performance of 3 NITs was evaluated according to the etiology of liver disease, sex,metabolic syndrome, obesity, and increased aminotransferase levels in 4 age groups. The APRI generally showed the best area under the receiver operating characteristic curve in patients aged 45 years or younger, and it was statistically significant in patients with chronic viral hepatitis and alcoholic fatty liver disease (P < .043). The best APRI cut-off value for detecting advanced hepatic fibrosis was 0.4, with a sensitivity and specificity of 75.8% and 73.5%, respectively, in the community-based cohort. The APRI showed balanced sensitivity and specificity across all age groups, whereas the other metrics showed low sensitivity in those aged <45 and low specificity in those >65 years. The APRI showed better sensitivity and negative predictive value than the Fibrosis-4 index and the nonalcoholic fatty liver disease fibrosis score in community-based populations with mixed etiology, and, thus, can be performed as the primary test in young adults (age, ≤45 y).

Red blood cell distribution width derivatives in alcohol-related liver cirrhosis and metabolic-associated fatty liver disease

BACKGROUNDLooking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring. There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIMTo study red blood cell distribution width (RDW), RDW-to-platelet ratio (RPR) and RDW-to-lymphocyte ratio (RLR) in alcohol-related liver cirrhosis (ALC) and metabolic-associated fatty liver disease (MAFLD).METHODSThe study group was composed of 302 people: 142 patients with ALC and 92 with MAFLD; 68 persons were included as controls. RDW, RPR and RLR were measured in each person. Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index (APRI), fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio (GPR), procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin]. MELD score in ALC patients and non-alcoholic fatty liver disease (NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group. The achieved results were compared to controls. Then a correlation between assessed markers was done. Diagnostic value of each investigated parameter and its suggested cut-off in the research group were evaluated with area under the curve (AUC).RESULTSRDW, RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls (ALC: P < 0.0001; NAFLD: P < 0.05, P < 0.0001 and P < 0.0001, respectively). RPR correlated positively with MELD score (P < 0.01) and indirect indices of liver fibrosis (FIB-4 and GPR; P < 0.0001) in ALC patients; negative correlations were found between PDGF-AB and both: RDW and RPR (P < 0.01 and P < 0.0001, respectively). RPR correlated positively with NAFLD fibrosis score and APRI (P < 0.0001) in the MAFLD group; a positive relationship was observed between RDW and FIB-4, too (P < 0.05). AUC values and suggested cut-offs for RDW, RPR and RLR in ALC patients were: 0.912 (> 14.2%), 0.965 (> 0.075) and 0.914 (> 8.684), respectively. AUC values and suggested cut-offs for RDW, RPR and RLR in MAFLD patients were: 0.606 (> 12.8%), 0.724 (> 0.047) and 0.691 (> 6.25), respectively.CONCLUSIONRDW with its derivatives appear to be valuable diagnostic markers in patients with ALC. They can also be associated with a deterioration of liver function in this group.

Impact of advanced liver fibrosis on atrial fibrillation recurrence after ablation in non-alcoholic fatty liver disease patients.

AimAdvanced liver fibrosis is independently associated with new onset of atrial fibrillation (AF). Non-invasive liver fibrosis scores are considered an effective strategy for assessing liver fibrosis. This study aimed to investigate the association between advanced liver fibrosis and AF recurrence after ablation in patients with non-alcoholic fatty liver disease (NAFLD).Materials and methodsA total of 345 AF patients with NAFLD who underwent de novo ablation between 2019 and 2020 at two large hospitals in China were included in this study. AF recurrence was defined as the occurrence of atrial arrhythmia for more than 30 s by electrocardiogram or 24 h Holter monitoring after the first 3 months of ablation. Predictive values of non-alcoholic fatty liver disease fibrosis score (NFS) and Fibrosis-4 (FIB-4) scores for AF burden and recurrence after ablation were assessed.ResultsAt the 1 year follow-up after ablation, 38.8% of patients showed recurrence. Patients with recurrence who had higher FIB-4 and NFS scores were more likely to have persistent AF and a duration of AF ≥ 3 years. In Kaplan–Meier analysis, patients with intermediate and high NFS and FIB-4 risk categories had a higher risk of AF recurrence. Compared to patients with the low risk, intermediate and high NFS, and FIB-4 risk were independently associated with AF recurrence in multivariate Cox regression analysis (high risk: NFS, hazard ratio (HR): 3.11, 95% confidence interval (CI): 1.68∼5.76, p < 0.001; FIB-4, HR: 3.91, 95% CI: 2.19∼6.98, p < 0.001; intermediate risk: NFS, HR: 1.85, 95% CI: 1.10∼3.10, p = 0.020; FIB-4, HR: 2.08, 95% CI: 1.27∼3.41, p = 0.003).ConclusionNFS and FIB-4 scores for advanced liver fibrosis are associated with AF burden. Advanced liver fibrosis is independently associated with AF recurrence following ablation. Advanced liver fibrosis might be meaningful in risk classification for patients after AF ablation.

High liver fibrosis scores in metabolic dysfunction-associated fatty liver disease patients are associated with adverse atrial remodeling and atrial fibrillation recurrence following catheter ablation.

BackgroundA number of epidemiological studies have suggested an association between metabolic dysfunction-associated fatty liver disease (MAFLD) and the incidence of atrial fibrillation (AF). However, the pathogenesis leading to AF in the context of MAFLD remains unclear. We therefore aimed at assessing the impact of MAFLD and liver fibrosis status on left atrium (LA) structure and function.MethodsPatients with a Fatty Liver Index (FLI) >60 and the presence of metabolic comorbidities were classified as MAFLD+. In MAFLD+ patients, liver fibrosis severity was defined using the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS), as follows: MAFLD w/o fibrosis (NFS ≦ −1.455), MAFLD w/indeterminate fibrosis (−1.455 < NFS < 0.675), and MAFLD w/fibrosis (NFS ≧ 0.675). In the first cohort of patients undergoing AF ablation, the structural and functional impact on LA of MAFLD was assessed by LA strain analysis and endocardial voltage mapping. Histopathological assessment of atrial fibrosis was performed in the second cohort of patients undergoing cardiac surgery. Finally, the impact of MAFLD on AF recurrence following catheter ablation was assessed.ResultsIn the AF ablation cohort (NoMAFLD n = 123; MAFLD w/o fibrosis n = 37; MAFLD indeterm. fibrosis n = 75; MAFLD w/severe fibrosis n = 10), MAFLD patients with high risk of F3–F4 liver fibrosis presented more LA low-voltage areas as compared to patients without MAFLD (16.5 [10.25; 28] vs 5.0 [1; 11] low-voltage areas p = 0.0115), impaired LA reservoir function assessed by peak left atrial longitudinal strain (19.7% ± 8% vs 8.9% ± 0.89% p = 0.0268), and increased LA volume (52.9 ± 11.7 vs 43.5 ± 18.0 ml/m2 p = 0.0168). Accordingly, among the MAFLD patients, those with a high risk of F3–F4 liver fibrosis presented a higher rate of AF recurrence during follow-up (p = 0.0179). In the cardiac surgery cohort (NoMAFLD n = 12; MAFLD w/o fibrosis n = 5; MAFLD w/fibrosis n = 3), an increase in histopathological atrial fibrosis was observed in MAFLD patients with a high risk of F3–F4 liver fibrosis (p = 0.0206 vs NoMAFLD; p = 0.0595 vs MAFLD w/o fibrosis).ConclusionIn conclusion, we found that liver fibrosis scoring in MAFLD patients is associated with adverse atrial remodeling and AF recurrences following catheter ablation. The impact of the management of MAFLD on LA remodeling and AF ablation outcomes should be assessed in dedicated studies.

Association between Coronary Artery Plaque Progression and Liver Fibrosis Biomarkers in Population with Low Calcium Scores.

Background: The severity of nonalcoholic fatty liver disease (NAFLD) has been found to be associated with atherosclerosis burden. However, whether liver fibrosis scores can be used to predict atherosclerosis progression, especially for patients with low calcium scores, remains undetermined. Methods: A total of 165 subjects who underwent repeated coronary computed tomography angiography (CCTA) and had low calcium scores (<100) were enrolled. The segment stenosis score (SSS) from the CCTA was measured, and the association between SSS progression and biochemical parameters was analyzed in addition to liver fibrosis scores, including nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), and Forns score. Results: When compared with those without plaque at baseline (SSS = 0), subjects with plaque had higher blood pressure, higher coronary artery calcium (CAC) scores, and higher liver fibrosis scores, including Forns score, Fib-4, and NFS. During the medium follow-up interval of 24.7 months, 60 (39.4%) patients displayed SSS progression, while the remaining 105 (63.6%) patients showed no CAD progression. In a multivariate analysis, being male having a high diastolic blood pressure (DBP), and having a high NFS liver fibrosis score were independently associated with the odds ratio for SSS progression. Conclusions: Higher baseline blood pressure and liver fibrosis markers are associated with the presence of coronary artery disease (CAD) plaques in subjects in early CAD stages. For disease progression, the male gender, DBP, and NFS appear to be independently associated with coronary atherosclerosis plaque progression in subjects with low calcium scores.

Accurate liquid biopsy for the diagnosis of non-alcoholic steatohepatitis and liver fibrosis

ObjectiveClinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis.DesignThis...