Do biomarkers matter? Cardiovascular risk stratification in Asian patients with metabolic dysfunction-associated steatotic liver disease in the era of fibrosis-centric assessment

Table 1 Selected Asian cohort studies linking metabolic dysfunction-associated steatotic liver disease or metabolic dysfunction-associated steatotic liver disease to cardiovascular outcomes

Ref.	Study population	Sample size	Outcome	Key finding	Effect size
[21]	Korea	9584399	Composite CVD event	MASLD identified a larger, more cardiometabolically complex population than MASLD	HR 1.43 for MASLD-only; HR 1.56 for both-FLD vs neither
[22]	Korea	351068	Incident MI or stroke	MASLD independently increased CVD risk	SHR 1.19 vs no SLD
[23]	Korea	104399	Incident CVD	Excess risk in MASLD concentrated in FIB-4-defined fibrosis	HR 2.27 for MASLD with FIB-4 ≥ 1.3
[24]	Taiwan	26676	Incident HF	MASLD associated with HF, especially HFpEF	SHR 2.59 for HF; SHR 1.91 for HFpEF
[25]	Korea	2773	Coronary artery calcification	Both labels associated with CAC, but MASLD tracked severe CAC more consistently	aOR 1.21 for CAC and 1.38 for severe CAC
[26]	China	203	Obstructive CAD and high-risk plaque	MASLD predicted adverse plaque anatomy and physiology	aOR 2.44 for obstructive CAD; 2.52 for HRP; 3.53 for FFRCT ≤ 0.8
[27]	Taiwan	6058	Coronary artery calcification	FIB-4 provided incremental referral value within MASLD	OR 1.217 per FIB-4 unit for CAC presence
[28]	Korea	8622	Any plaque and obstructive CAD	SAFE score and MASLD both stratified subclinical coronary atherosclerosis	MASLD OR 3.64 for obstructive CAD; higher SAFE strongly associated with plaque and obstruction

CVD: Cardiovascular disease; MASLD: Metabolic dysfunction-associated steatotic liver disease; HR: Hazard ratio; FLD: Fatty liver disease; MI: Myocardial infarction; SHR: Subdistribution hazard ratio; SLD: Steatotic liver disease; FIB-4: Fibrosis-4 index 4; HF: Heart failure; HFpEF: Heart failure with preserved ejection fraction; CAC: Coronary artery calcium; aOR: Adjusted odds ratio; CAD: Coronary artery disease; HRP: Hazard ratio point; FFRCT: Fractional flow reserve derived from computed tomography; OR: Odds ratio; SAFE: Steatosis-activity-fibrosis evaluation index.

Table 2 Biomarker-centred studies relevant to cardiovascular risk stratification in Asian patients with metabolic dysfunction-associated steatotic liver disease or closely overlapping fatty liver phenotypes

Biomarker	Study population	Sample size	Key finding	Effect size or performance
UHR[43]	Lean Chinese adults with MASLD by ultrasound	6285	UHR independently associated with MASLD; marked gradient across quintiles	OR 1.105 per unit; prevalence 191% to 24.54% across quintiles
UHR[44]	Non-obese Chinese adults with normal lipids, 5-year follow-up	9837	UHR predicted incident MASLD better than uric acid or HDL alone	HR 1.76 in highest quintile; AUC: 0.690; sensitivity: 71%
UHR[45]	Chinese case-control MASLD study	1390	Strong positive dose-response relation between UHR and MASLD	OR: 3.888, highest vs lowest quartile
UHR[46]	Lean Chinese patients with type 2 diabetes	343	UHR useful for MASLD discrimination in non-overweight diabetes	AUC: 0.697; sensitivity: 0.761; specificity: 0.553
hs-CRP[47]	North Indian MASLD case-control study	200	hs-CRP rose with MASLD and severity	Adjusted OR: 1.311; mean: 3.12 mg/L vs 1.05 mg/L
TyG[48]	Chinese MASLD patients with chest pain undergoing angiography	424	TyG associated with prevalent CHD and angiographic severity	OR 2.519 for CHD; per 1-unit OR 2.06; β 2.44 in Gensini per 0.1-unit
TyG[49]	Chinese MASLD cohort with carotid follow-up	739	TyG predicted incident carotid atherosclerosis	HR 3.11 in Q2 and 4.51 in Q3 vs Q1
FIB-4, NFS, WFA+-M2BP[39]	Japanese prospective screening cohort	3512	Advanced fibrosis markers independently linked to high CV risk	Fatty liver plus advanced fibrosis OR 5.90-35.6 for high Framingham risk
FIB-4[50]	Korean MASLD prospective cohort	104399	Fibrosis enriched incident CVD risk in MASLD	HR 2.27 for CVD when FIB-4 ≥ 1.3
FIB-4[40]	Taiwanese MASLD-CAC referral study	6058	FIB-4 associated with CAC beyond MASLD status	OR 1.217 for CAC presence

UHR: Uric acid/high-density lipoprotein cholesterol ratio; MASLD: Metabolic dysfunction-associated steatotic liver disease; OR: Odds ratio; HDL: High-density lipoprotein; HR: Hazard ratio; AUC: Area under the curve; hs-CRP: High-sensitivity C-reactive protein; TyG: Triglyceride-glucose; CHD: Coronary heart disease; FIB-4: Fibrosis-4 index 4; NFS: Non-alcoholic fatty liver disease fibrosis score; WFA+-M2BP: Wisteria floribunda agglutinin-positive Mac-2 binding protein; CV: Cardiovascular; CVD: Cardiovascular disease; CAC: Coronary artery calcium.