Skip to content
2000
image of The Association Between Telomere Length and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Abstract

Introduction

Studies have stated that there has been a close association between the telomere length (TL) and the incidence of non-alcoholic fatty liver disease (NAFLD). The goal of this report is to explore the possible association between TL and NAFLD.

Methods

This study adhered to the PRISMA guidelines for systematic reviews. An extensive literature search was conducted in the Cochrane Library, CINAHL, Scopus, PubMed, and Web of Science. The “meta” package in the R programming language, version 4.3.1, was used for statistical analysis.

Results

The meta-analysis of the included studies showed a pooled standard mean difference (SMD) of -0.25 (95% CI: -0.39 to -0.10), indicating shorter TL in NAFLD patients. Subgroup analyses revealed significant TL shortening in NAFLD patients with body mass index (BMI) <28 (SMD = -0.68, 95% CI: -0.96 to -0.39) and in case-control (-0.35, 95% CI: -0.51 to -0.20) and cohort studies (-0.68, 95% CI: -1.19 to -0.17). An odds ratio (OR) meta-analysis of six studies found that individuals with short TL had 1.72 times higher odds of NAFLD, which was statistically significant (95% CI: 1.23-2.42, I2 = 85%). Excluding one study reduced heterogeneity (I2 = 37%) and increased the OR to 1.93 (95% CI: 1.45-2.56), confirming a strong association between short TL and NAFLD risk.

Discussion

The findings suggest a potential link between shorter TL and NAFLD. The odds ratio analyses further emphasized the increased risk of NAFLD in individuals with short TL. Nevertheless, the residual heterogeneity highlights the need for further high-quality, standardized research.

Conclusion

Our findings supported the connection between reduced TL and NAFLD. Regardless of significant between-study diversity, the results remained consistent even after repeated sensitivity evaluations. Despite these findings, the high heterogeneity highlights the need for further well-designed studies to confirm TL as a reliable biomarker for NAFLD risk and progression.

© Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240360593250805102356
2025-09-11
2025-12-13

  • From This Site

    /content/journals/cmm/10.2174/0115665240360593250805102356
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Ayonrinde O.T. Historical narrative from fatty liver in the nineteenth century to contemporary NAFLD – Reconciling the present with the past. JHEP Reports 2021 3 3 100261 10.1016/j.jhepr.2021.100261 34036255
    [Google Scholar]
  2. Loomba R. Friedman S.L. Shulman G.I. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 2021 184 10 2537 2564 10.1016/j.cell.2021.04.015 33989548
    [Google Scholar]
  3. Pouwels S. Sakran N. Graham Y. Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss. BMC Endocr. Disord. 2022 22 1 63 10.1186/s12902‑022‑00980‑1 35287643
    [Google Scholar]
  4. Chen Y. Wang W. Morgan M.P. Robson T. Annett S. Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: Current status and therapeutic targets. Front. Endocrinol. 2023 14 1148934 10.3389/fendo.2023.1148934 37361533
    [Google Scholar]
  5. Donati B. Pietrelli A. Pingitore P. Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease. Cancer Med. 2017 6 8 1930 1940 10.1002/cam4.1078 28677271
    [Google Scholar]
  6. Ping F. Li Z. Lv K. Deoxyribonucleic acid telomere length shortening can predict the incidence of non‐alcoholic fatty liver disease in patients with type 2 diabetes mellitus. J. Diabetes Investig. 2017 8 2 174 180 10.1111/jdi.12555 27451965
    [Google Scholar]
  7. Dongiovanni P. Romeo S. Valenti L. Hepatocellular carcinoma in nonalcoholic fatty liver: Role of environmental and genetic factors. World J. Gastroenterol. 2014 20 36 12945 12955 10.3748/wjg.v20.i36.12945 25278690
    [Google Scholar]
  8. Laish I. Mannasse-Green B. Hadary R. Telomere dysfunction in nonalcoholic fatty liver disease and cryptogenic cirrhosis. Cytogenet. Genome Res. 2016 150 2 93 99 10.1159/000454654 28006764
    [Google Scholar]
  9. Huang D.Q. Tran S. Barnett S. Incidence and predictors of hepatocellular carcinoma in NAFLD without diagnosed cirrhosis: A nationwide real-world U.S. study. Hepatol. Int. 2024 18 2 540 549 10.1007/s12072‑023‑10616‑8 38079023
    [Google Scholar]
  10. Dhamija E. Paul S.B. Kedia S. Non-alcoholic fatty liver disease associated with hepatocellular carcinoma. Indian J. Med. Res. 2019 149 1 9 17 10.4103/ijmr.IJMR_1456_17 31115369
    [Google Scholar]
  11. Zhang W. Zhang J. Shi H. Liu F. Yu H. Shi H. Exosome GLUT1 derived from hepatocyte identifies the risk of non-alcoholic steatohepatitis and fibrosis. Hepatol. Int. 2023 17 5 1170 1181 10.1007/s12072‑023‑10520‑1 37278869
    [Google Scholar]
  12. Laish I. Mannasse-Green B. Hadary R. Konikoff F.M. Amiel A. Kitay-Cohen Y. Aneuploidy and asynchronous replication in non-alcholic fatty liver disease and cryptogenic cirrhosis. Gene 2016 593 1 162 166 10.1016/j.gene.2016.08.017 27520584
    [Google Scholar]
  13. Meijnikman A.S. Herrema H. Scheithauer T.P.M. Kroon J. Nieuwdorp M. Groen A.K. Evaluating causality of cellular senescence in non-alcoholic fatty liver disease. JHEP Reports 2021 3 4 100301 10.1016/j.jhepr.2021.100301 34113839
    [Google Scholar]
  14. Rossiello F. Jurk D. Passos J.F. d’Adda di Fagagna F. Telomere dysfunction in ageing and age-related diseases. Nat. Cell Biol. 2022 24 2 135 147 10.1038/s41556‑022‑00842‑x 35165420
    [Google Scholar]
  15. Huang W. Hickson L.J. Eirin A. Kirkland J.L. Lerman L.O. Cellular senescence: The good, the bad and the unknown. Nat. Rev. Nephrol. 2022 18 10 611 627 10.1038/s41581‑022‑00601‑z 35922662
    [Google Scholar]
  16. Dong K. Zhang Y. Huang J.J. Xia S.S. Yang Y. Shorter leucocyte telomere length as a potential biomarker for nonalcoholic fatty liver disease-related advanced fibrosis in T2DM patients. Ann. Transl. Med. 2020 8 6 308 10.21037/atm.2020.03.10 32355752
    [Google Scholar]
  17. Révész D. Verhoeven J.E. Picard M. Associations between cellular aging markers and metabolic syndrome: Findings from the CARDIA study. J. Clin. Endocrinol. Metab. 2018 103 1 148 157 10.1210/jc.2017‑01625 29053810
    [Google Scholar]
  18. Young N.S. Telomere biology and telomere diseases: Implications for practice and research. Hematology 2010 2010 1 30 35 10.1182/asheducation‑2010.1.30 21239767
    [Google Scholar]
  19. Ball S.E. Gibson F.M. Rizzo S. Tooze J.A. Marsh J.C.W. Gordon-Smith E.C. Progressive telomere shortening in aplastic anemia. Blood 1998 91 10 3582 3592 10.1182/blood.V91.10.3582 9572992
    [Google Scholar]
  20. Savage S.A. Giri N. Baerlocher G.M. Orr N. Lansdorp P.M. Alter B.P. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am. J. Hum. Genet. 2008 82 2 501 509 10.1016/j.ajhg.2007.10.004 18252230
    [Google Scholar]
  21. Mushiroda T. Wattanapokayakit S. Takahashi A. A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J. Med. Genet. 2008 45 10 654 656 10.1136/jmg.2008.057356 18835860
    [Google Scholar]
  22. Calado R.T. Regal J.A. Kleiner D.E. A spectrum of severe familial liver disorders associate with telomerase mutations. PLoS One 2009 4 11 7926 10.1371/journal.pone.0007926 19936245
    [Google Scholar]
  23. Tang L. Li D. Ma Y. Cui F. Wang J. Tian Y. The association between telomere length and non-alcoholic fatty liver disease: A prospective study. BMC Med. 2023 21 1 427 10.1186/s12916‑023‑03136‑7 37940980
    [Google Scholar]
  24. Zhang M. Hu M.L. Huang J.J. Xia S.S. Yang Y. Dong K. Association of leukocyte telomere length with non-alcoholic fatty liver disease in patients with type 2 diabetes. Chin. Med. J. 2019 132 24 2927 2933 10.1097/CM9.0000000000000559 31809318
    [Google Scholar]
  25. Moher D. Liberati A. Tetzlaff J. Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann. Intern. Med. 2009 151 4 264 269 10.7326/0003‑4819‑151‑4‑200908180‑00135
    [Google Scholar]
  26. Grammatopoulos T. Hunter J.W.S. Munn Z. Stone J.C. Barker T.H. Reporting quality and risk of bias in JBI systematic reviews evaluating the effectiveness of interventions: A methodological review protocol. JBI Evidence Synthesis 2023 21 3 584 591 10.11124/JBIES‑22‑00317 36632760
    [Google Scholar]
  27. McGrath S. Zhao X. Steele R. Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis. Stat. Methods Med. Res. 2020 29 9 2520 2537 10.1177/0962280219889080 32292115
    [Google Scholar]
  28. Viechtbauer W. Cheung M.W.L. Outlier and influence diagnostics for meta-analysis. Res. Synth. Methods 2010 1 2 112 125 10.1002/jrsm.11 26061377
    [Google Scholar]
  29. Zhang J. Zang S. Yang W. Chen Y. Zhuang Z. Luo Y. Shortened leucocyte telomere length is associated independently with fibrosis stage in non-alcoholic fatty liver disease. Int. J. Clin. Exp. Med. 2017 10 11204 11212
    [Google Scholar]
  30. Kim D. Li A.A. Ahmed A. Leukocyte telomere shortening predicts nonalcoholic fatty liver disease-related advanced fibrosis. Gastroenterology 2018 154 6 S1163
    [Google Scholar]
  31. Wojcicki J.M. Rehkopf D. Epel E. Rosenthal P. Shorter leukocyte telomere length in relation to presumed nonalcoholic fatty liver disease in mexican-american men in nhanes 1999–2002. Int. J. Hepatol. 2017 2017 1 7 10.1155/2017/8435178 28740738
    [Google Scholar]
  32. Wojcicki J.M. Gill R.M. Wilson L. Lin J. Rosenthal P. Shorter leukocyte telomere length protects against NAFLD progression in children. Sci. Rep. 2023 13 1 5446 10.1038/s41598‑023‑31149‑y 37012261
    [Google Scholar]
  33. Aravinthan A. Scarpini C. Tachtatzis P. Hepatocyte senescence predicts progression in non-alcohol-related fatty liver disease. J. Hepatol. 2013 58 3 549 556 10.1016/j.jhep.2012.10.031 23142622
    [Google Scholar]
  34. Shin H.K. Park J.H. Yu J.H. Association between telomere length and hepatic fibrosis in non-alcoholic fatty liver disease. Sci. Rep. 2021 11 1 18004 10.1038/s41598‑021‑97385‑2 34504179
    [Google Scholar]
  35. Emelyanov D.V. Galchynska V.Y. Bondar T.M. Marker of gingival epithelial cell aging in patients with non-alcoholic fatty liver disease. Modern Gastroenterology 2023 2023 1 19 23 10.30978/MG‑2023‑1‑19
    [Google Scholar]
  36. Nakajima T. Moriguchi M. Katagishi T. Premature telomere shortening and impaired regenerative response in hepatocytes of individuals with NAFLD. Liver Int. 2006 26 1 23 31 10.1111/j.1478‑3231.2005.01178.x 16420506
    [Google Scholar]
  37. Kandemir I. Sahin A.Y. Oyaci Y. Effect of obesity and NAFLD on leukocyte telomere length and hTERT gene MNS16A VNTR variant. Sci. Rep. 2024 14 1 25055 10.1038/s41598‑024‑77091‑5 39443618
    [Google Scholar]
  38. Moreno E. Martínez-Sanz J. Martín-Mateos R. Global DNA methylation and telomere length as markers of accelerated aging in people living with HIV and non-alcoholic fatty liver disease. BMC Genomics 2023 24 1 567 10.1186/s12864‑023‑09653‑2 37741970
    [Google Scholar]
  39. Korkiakoski A. Käräjämäki A.J. Ronkainen J. Nonalcoholic fatty liver disease and its prognosis associates with shorter leucocyte telomeres in a 21-year follow-up study. Scand. J. Clin. Lab. Invest. 2022 82 3 173 180 10.1080/00365513.2022.2059698 35416741
    [Google Scholar]
  40. Alqahtani S.A. Schattenberg J.M. NAFLD in the elderly. Clin. Interv. Aging 2021 16 1633 1649 10.2147/CIA.S295524 34548787
    [Google Scholar]
  41. Guo J. Huang X. Dou L. Aging and aging-related diseases: From molecular mechanisms to interventions and treatments. Signal Transduct. Target. Ther. 2022 7 1 391 10.1038/s41392‑022‑01251‑0 36522308
    [Google Scholar]
  42. Nakajima T. Nakashima T. Okada Y. Nuclear size measurement is a simple method for the assessment of hepatocellular aging in non-alcoholic fatty liver disease: Comparison with telomere-specific quantitative FISH and p21 immunohistochemistry. Pathol. Int. 2010 60 3 175 183 10.1111/j.1440‑1827.2009.02504.x 20403043
    [Google Scholar]
  43. Amano H. Chaudhury A. Rodriguez-Aguayo C. Telomere dysfunction induces sirtuin repression that drives telomere-dependent disease. Cell Metab. 2019 29 6 1274 1290.e9 10.1016/j.cmet.2019.03.001 30930169
    [Google Scholar]
  44. Richardson M.M. Jonsson J.R. Powell E.E. Progressive fibrosis in nonalcoholic steatohepatitis: Association with altered regeneration and a ductular reaction. Gastroenterology 2007 133 1 80 90 10.1053/j.gastro.2007.05.012 17631134
    [Google Scholar]
  45. Kim D. Li A.A. Ahmed A. Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease‐related advanced fibrosis. Liver Int. 2018 38 10 1839 1848 10.1111/liv.13886 29797393
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240360593250805102356
Loading
The Association Between Telomere Length and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Bentham Science Publishers ; https://doi.org/10.2174/0115665240360593250805102356
/content/journals/cmm/10.2174/0115665240360593250805102356
/content/journals/cmm/10.2174/0115665240360593250805102356
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article. The PRISMA checklist is also provided as supplementary material on the publisher’s website.

file format download Download

  • Article Type:     Research Article
Keywords: Nonalcoholic fatty liver disease (NAFLD) ; hepatocellular carcinoma ; non-alcoholic steatohepatitis (NASH) ; telomere length (TL)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test