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Page 8 of 22 Ballestri et al. Metab Target Organ Damage 2023;3:1 https://dx.doi.org/10.20517/mtod.2022.23

Among MAFLD individuals, having a low muscle mass was associated with a higher risk of
significant liver fibrosis (OR = 1.56 to 2.43; P < 0.001), and similar findings were observed when
significant hepatic fibrosis was defined with NFS
Longitudinal

[62]
Chen et al. A prospective cohort study enrolling 3263 CAD 319 out of 538 deaths observed during this study were due to CVD Among CAD patients, higher liver fibrosis
Chinese patients submitted to a median follow-up Multivariable-adjusted HRs (95%CI) for those with the highest levels of NFS, FIB-4, APRI, GPR, scores and noninvasive biomarkers are
period of 7.56 years (inter-quartile range: 6.86- and Forns score were 2.89 (2.14-3.91), 2.84 (2.14-3.76), 1.77 (1.33-2.36), 1.47 (1.19-1.83) and associated with increased mortality owing to all
8.31) 3.10 (1.88-5.11) for all-cause mortality, 3.02 (2.05-4.45), 3.34 (2.29-4.86), 1.99 (1.40-2.83), 1.80 causes and CVD
Cox models were used to assess the association (1.36-2.39) and 2.43 (1.28-4.61) for CV mortality, respectively, compared to patients with lowest
of baseline levels of NFS; FIB-4; APRI; GPR, and score levels
Forns score, with the risk of all-cause and CV These associations were consistent after ruling out early deaths (i.e., those occurring within the
mortality among CAD patients first year of follow-up) or stratifying patients (by sex, age, BMI, diabetes status, MetS status,
CAD type, and hsCRP level)
Barattta 898 consecutive outpatients (mean age, 56.4 ± CVEs rate was higher in patients with (2.1%/year) than without NAFLD (1.0%/year) (P > 0.05) Liver fibrosis indexes are strongly associated
[63]
et al. 12.7 years; 37.5% women) underwent US to At Cox MVA, NAFLD significantly increased the risk of CVEs (HR 2.41) after adjusting for MetS. with incident CVEs among NAFLD individuals
identify liver steatosis Among NAFLD patients, male sex, previous CVEs, MetS, and FIB-4 scores > 2.67 (HR 4.02; P <
Liver fibrosis was defined as a FIB-4 score > 2.67 0.05) were independently associated with the risk of incident CVEs. NFS scores > 0.676 were
and NFS > 0.676 also independently associated with the risk of incident CVEs (HR 2.35; P < 0.05)
Phone interviews were conducted every 6
months, and patients were examined every 12
months in the outpatient clinic. Median follow-up
time of 41.4 months (3044.4 patient-years)
Primary outcomes: incidence rate of CVEs defined
as fatal or nonfatal ischemic stroke and MI,
cardiac or peripheral revascularization, new-onset
AF, and CV death
[64]
Lee et al. 1173 asymptomatic adults with CAC scores from The mean baseline FIB-4 score was significantly higher in subjects with CAC Noninvasively assessed advanced liver fibrosis
2007-2013 were enrolled. Median follow-up: 3.0 CAC progression rates were 20.5%, 27.5%, and 35.9% among those NAFLD-free, with NAFLD associates with an increased chance of CAC
(2.0-3.8) years and low FIB-4 values, and those with NAFLD and intermediate/high FIB-4 scores, respectively progression among NAFLD patients
CAC progression was defined as newly incident At MVA, compared to NAFLD-free controls, subjects with NAFLD plus intermediate/high FIB-4
CAC or a ≥ 2.5-unit increase in the final CAC scores had OR for CAC progression = 1.70 after adjustment for sex, BMI, smoking, drinking,
score square root exercise, hypertension, T2D, serum TG, HDL-C, LDL-C, and hsCRP
Liver fibrosis was assessed with FIB-4 and NFS In the sensitivity analysis, the OR for CAC progression was 1.57 for subjects with NAFLD plus an
intermediate/high NFS versus those without NAFLD
[65]
Liu et al. Multicenter, prospective study, enrolling 4003 Subjects who developed MACE were likelier to have either intermediate or high values of NFS; High values of hepatic fibrosis markers predict
consecutive patients with stable CAD undergoing FIB-4; BARD; and ARR adverse outcomes in patients with stable CAD
PCI and followed up for an average of 5.0 ± 1.6 Moreover, compared to individuals who had low fibrosis markers scores, those with intermediate submitted to PCI, suggesting that these
years the occurrence of MACE (CV death, non- plus high score levels had significantly increased risk of MACE (aHR 1.57-1.92) after adjustment markers might also be evaluated in the risk
fatal MI, and stroke) for age, sex, smoking, drinking, T2D, hypertension, SBP, LDL-C, HbA1c, hs-CRP, number of lesion stratification before elective PCI
vessels and baseline statin use
Finally, the prediction ability of a model with established CV risk factors significantly improved by
adding NFS, FIB-4, or BAARD
Peters Data from 1423 individuals with HFpEF from the Advanced fibrosis (defined by high fibrosis scores) was present in 37.57% of the NFS and 8.02% Advanced liver fibrosis (assessed with fibrosis
[66]
et al. TOPCAT trial were analyzed by the FIB-4 biomarkers) may not be uncommon among
The risk of advanced liver fibrosis was classified In unadjusted models, the risk of advanced fibrosis was significantly associated with the primary HFpEF patients
as low, intermediate, and high based on NFS and CV outcome (NFS high vs. low: HR 1.71; FIB-4 high vs. low: HR 1.56). However, this association There seems to be a limited independent
FIB-4 scores was diminished (NFS high vs. low: HR 1.35, P > 0.05); FIB-4 high vs. low: HR 1.42, P = 0.05) after association between liver fibrosis risk scores