S2648 Association of NAFLD Severity With Major Adverse Cardiovascular Events: A Meta-Analysis of Cohort Studies
Bibliographic record
Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD), a primary hepatic manifestation of metabolic syndrome, is now recognized as a significant contributor to cardiovascular disease burden. It is unclear whether advanced NAFLD severity independently predicts major adverse cardiovascular events (MACE) because severity has not been consistently defined, and few considered potential confounding factors. Methods: Following the PRISMA 2020 guidelines, we looked through the Cochrane Library, Web of Science, Embase, and PubMed till January 2025 for longitudinal cohort studies assessing MACE incidence according to NAFLD severity. Eligible studies included adults with biopsy-verified (NASH or fibrosis ≥ F2) or imaging-verified (MRI-PDFF ≥10% or CAP ≥280 dB/m) NAFLD and stratified as mild vs moderate/severe, with an average follow-up of 1 year or greater. Two reviewers separately conducted the data extraction and assessed for bias using the Newcastle-Ottawa Scale. Ninety-five percent confidence intervals (CI) and pooled risk ratios (RR) were determined using a random-effects model. Heterogeneity (I²) and small-study effects (Egger's test) were assessed. Sensitivity analyses were performed to exclude studies at high risk of bias. Results: Three cohort studies met inclusion criteria for MACE outcomes (N = 136,789; mean age: 52–58; duration: 5.2–8.1 years). One study on advanced (F3–F4/NASH) and mild (F0–F1/steatosis) NAFLD calculated a fully adjusted RR of 1.50 (95% CI 0.97–2.32; P = 0.07), indicating a trend towards greater MACE risk. The pooled RR for NAFLD, compared to no NAFLD, was 1.19 (95% CI 0.80-1.79; I² = 94%) with sensitivity analysis RR (95% CI) 1.12 (0.85-1.48). There is a pooled RR for MACE among NAFLD cases across all severity strata of 1.26 (95% CI 0.92-1.73; I² = 88%). Egger's test did not report evidence of publication bias (P = 0.34). Only 1 study controlled for diabetes and dyslipidemia, and none for visceral adiposity. Conclusion: This meta-analysis suggests that histologically or imaging-defined advanced NAFLD may be associated with a clinically meaningful but statistically insignificant increased risk of MACE. Substantial heterogeneity and residual confounding affect definitive interpretations. Future studies should employ standardized severity cutoffs (such as MRI-PDFF ≥10% or fibrosis stage ≥ F2), adjust for cardiometabolic risk factors, and distinguish the atherosclerotic and non-atherosclerotic MACE components to strengthen the prediction of cardiovascular risk in NAFLD.
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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 | 0.029 | 0.055 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.015 | 0.061 |
| Bibliometrics | 0.007 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 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".