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The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe.

ABSTRACT: OBJECTIVE:The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. METHODS:We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke. Outcomes were compared between NFS categories and treatment arms using frequency of events, KM rates and adjusted Cox proportional hazard models. The ability of the NFS to predict recurrent CV events was independently validated in 5395 placebo-treated patients enrolled in the SOLID-TIMI 52 trial. RESULTS:Among 14,819 patients enrolled in IMPROVE-IT, 14.2% (N?=?2106) were high-risk (NFS?>?0.67). The high-risk group had a 30% increased risk of recurrent major CV events, compared to the low-risk NFS group (HR 1.30 [1.19-1.43]; p??0.67 vs. NFS?

SUBMITTER: Simon TG

PROVIDER: S-EPMC6139264 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe.

Simon Tracey G TG Corey Kathleen E KE Cannon Christopher P CP Blazing Michael M Park Jeong-Gun JG O'Donoghue Michelle L ML Chung Raymond T RT Giugliano Robert P RP

International journal of cardiology 20180526

<h4>Objective</h4>The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction.<h4>Methods</h4>We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death ...[more]

PMID: 29903515

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Project description:ImportanceThe diagnostic performance of the fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for advanced fibrosis in lean patients with NAFLD is limited.ObjectiveTo evaluate the diagnostic performance of the FIB-4 and NFS in lean individuals with NAFLD.Design, setting, and participantsThis diagnostic study included adults with biopsy-proven NAFLD from 6 referral centers in Asia from 1995 to 2019. Cohorts were matched by age and sex between the lean and nonlean groups. All statistical analyses were executed from October 2022 to March 2023.Main outcomes and measuresThe diagnostic performance of the FIB-4 and NFS at the current cutoff for advanced hepatic fibrosis in lean (body mass index [BMI] below 23 [calculated as weight in kilograms divided by height in meters squared]) and nonlean (BMI above 23) patients were evaluated.ResultsA total of 1501 patients were included in analysis (mean [SD] age, 46.1 [16.4] years); 788 male (52.5%), 115 lean (7.7%), 472 (30.2%) Korean, 821 (48.7%) Japanese, and 341 (21.3%) Taiwanese. Among the age- and sex-matched cohort, the mean (SD) age was 52.3 (15.1) years and 41.2% (47 of 114) were male. The diagnostic performance and areas under the operating characteristic curve of the FIB-4 (lean, 0.807 vs nonlean, 0.743; P = .28) and NFS (lean, 0.790 vs nonlean, 0.755; P = .54) between the 2 groups were comparable in the age- and sex-matched cohort. The sensitivity and specificity of the NFS showed increasing and decreasing tendency according to the BMI quartiles (P for trend < .001), while those of the FIB-4 did not (P for trend = .05 and P = .20, respectively). Additionally, although the areas under the operating characteristic curve of the FIB-4 and NFS were not significantly different in the lean group (0.807 vs 0.790; P = .09), the sensitivity of the current NFS cutoff values was lower in the lean group than in that of FIB-4 (54.4% vs 81.8%; P = .03).Conclusions and relevanceIn this cohort study, the performance of the FIB-4 and NFS in diagnosing advanced fibrosis did not differ significantly between the 2 groups overall. However, in lean NAFLD, while the sensitivity for diagnosing advanced hepatic fibrosis remained reasonable at the current cutoff level, the sensitivity of NFS at the current cutoff was too low to be an adequate screening tool.

Project description:OBJECTIVES:To investigate the use of MR elastography (MRE)-derived mechanical properties (shear stiffness (|G*|) and loss modulus (G?)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. METHODS:Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G?) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. RESULTS:The combination of FF, |G*|, and G? predicted NAS?>?1 with excellent accuracy in both training and testing sets (AUROC?>?0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between "not-NASH" and "definite-NASH." "Borderline-NASH" prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. CONCLUSION:This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. KEY POINTS:• MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC?>?0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80-92%. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.

Dataset Information

The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe.

Publications

The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe.

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