Evidence From a Systematic Review of Non-alcoholic Fatty Liver Disease (NAFLD)/Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Fueling Cardiovascular Risk
Bibliographic record
Abstract
Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is increasingly implicated as a key risk factor for cardiovascular disease (CVD). However, its independent contribution remains debated due to confounding metabolic factors and methodological heterogeneity. This review aims to synthesize evidence on the association between NAFLD/MASLD and cardiovascular outcomes, focusing on the influence of liver fibrosis and metabolic dysfunction. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched PubMed/MEDLINE, ScienceDirect, Europe PMC, and Cochrane Library (through May 2025) for observational studies and trials assessing NAFLD/MASLD and CVD outcomes in adults. NAFLD required imaging/biopsy or validated scores (fatty liver index (FLI) ≥30, Fibrosis-4 Index (FIB-4)); comparators were non-NAFLD controls. Outcomes included myocardial infarction, stroke, CVD mortality, and atherosclerosis. Two reviewers independently screened records, extracted data, and assessed risk of bias (Newcastle-Ottawa Scale (NOS)/Cochrane RoB 2). The systematic search identified 21 eligible studies (18 cohort, two cross-sectional, and one RCT). Sample sizes ranged widely, from a few hundred in clinical cohorts to over 9.5 million in a national database study. Observational studies demonstrated good methodological quality (mean NOS score ≥7/9). NAFLD/MASLD showed a consistent dose-dependent association with cardiovascular risk, with effect sizes ranging from modest (adjusted HR=1.2) to substantial (HR=8.0). Risk stratification revealed (i) advanced fibrosis (FIB-4 >2.67) quadrupled CVD risk (HR >4.5) and (ii) metabolic burden significantly amplified outcomes (HR=8.04 for ≥4 risk factors). While the association remained significant in most studies, rigorous adjustment for metabolic covariates attenuated effects in some analyses, suggesting that MASLD represents both an independent pathogenic factor and a metabolic dysfunction marker. NAFLD/MASLD is a significant risk factor for adverse cardiovascular outcomes, with the degree of risk strongly graded by the severity of liver fibrosis and metabolic comorbidity. While evidence is predominantly observational, these findings support integrating non-invasive fibrosis assessment into CVD risk stratification. Future research requires randomized trial testing whether MASLD-targeted therapies can reduce cardiovascular events.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.016 | 0.084 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.013 | 0.012 |
| Bibliometrics | 0.012 | 0.013 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".