Telomere length and metabolic dysfunction-associated steatotic liver disease risk and progression: A systematic review and meta-analysis

AIMS: This study aims to systematically review existing literature to evaluate the association between telomere length (TL) and the risk of MASLD and its progression outcomes. MATERIALS AND METHODS: PubMed, EMBASE, and Web of Science were searched for relevant studies up to May 27, 2025. Included studies were systematically reviewed to summarize the findings, with complementary quantitative analyses conducted using a random-effects model. This study was conducted in strict accordance with the PRISMA 2020 statement and was registered on the PROSPERO platform (CRD420251042478). RESULTS: Ultimately, 12 observational studies met the inclusion criteria. A limited number of high-quality cohort studies have consistently observed an association between shorter leukocyte TL (LTL) and an increased risk of MASLD. Evidence from cross-sectional studies appears more inconsistent and imprecise. Notably, cross-sectional analysis revealed a paradoxical increase in LTL among T2DM patients with MASLD, possibly reflecting a compensatory response to early-stage metabolic stress and insulin resistance; however, longitudinal evidence clarified that accelerated LTL attrition, rather than baseline length, serves as the critical driver and predictor of MASLD incidence. Despite consistent evidence indicating that shorter LTL may serve as a biomarker for severe MASLD progression, the interpretation of these findings is hampered by methodological limitations in current studies. CONCLUSION: Current evidence suggests that shorter TL is a potential marker for MASLD risk, particularly supported by high-quality longitudinal data. While further quantitative analysis identified significant associations, the robustness of these results is compromised by the limited number of high-quality studies, alongside substantial heterogeneity and publication bias. Shorter TL may be associated with the adverse progression of MASLD. Future high-quality longitudinal studies are warranted to strengthen the body of evidence and establish their clinical utility.