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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Statins and the Lifetime Outcomes of MASLD: From Evidence Asymmetry to Outcome Convergence

  • Javier Crespo1,2,3
  • Marta Alonso-Peña4,5
  • Carolina Jiménez-González5
  • Lorena Cayón-González5
  • Paula Iruzubieta5,6
6 affiliations
  1. 1Cantabria Cohort, Valdecilla Research Institute (IDIVAL), 39011 Santander, Spain
  2. 2Faculty of Medicine, University of Cantabria, 39011 Santander, Spain
  3. 3MedicineAI, 28027 Madrid, Spain
  4. 4Departmento de Anatomía y Biología Celular, Universidad de Cantabria, 39011 Santander, Spain
  5. 5Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), 39011 Santander, Spain
  6. 6Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain
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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic disorder in which cardiovascular, hepatic and oncological outcomes shape long-term prognosis. Statins are particularly relevant because their cardiovascular benefit is firmly established, yet they remain underused in MASLD, while their potential liver-related effects remain uncertain. Observational studies consistently associate statin exposure with slower fibrosis progression, fewer major adverse liver outcomes, lower hepatocellular carcinoma incidence and reduced liver-related mortality. However, direct randomized evidence in MASLD remains limited, and available studies differ substantially in disease stage, exposure, endpoint and follow-up. In this narrative review, we critically examine the cardiovascular, hepatic, oncological, randomized, observational, genetic and pharmacological evidence on statin therapy in MASLD. We aim to clarify the apparent discordance between evidence sources, assess whether statins may modify liver-related outcomes beyond their established cardiovascular benefit, and propose a framework for evaluating multidomain therapeutic effects. We propose outcome convergence as a framework for assessing whether a therapy can improve more than one clinically relevant disease domain while preserving independent causal evaluation of each outcome. Statins should therefore be regarded as a candidate, rather than an established, outcome-convergent therapy.

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Cite

BibTeXRIS
BibTeX
@article{crespo2026statins,
  title = {{Statins and the Lifetime Outcomes of MASLD: From Evidence Asymmetry to Outcome Convergence}},
  author = {Javier Crespo and Marta Alonso-Peña and Carolina Jiménez-González and Lorena Cayón-González and Paula Iruzubieta},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219407},
  url = {https://www.mdpi.com/1422-0067/27/21/9407},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Statins and the Lifetime Outcomes of MASLD: From Evidence Asymmetry to Outcome Convergence
AU  - Javier Crespo
AU  - Marta Alonso-Peña
AU  - Carolina Jiménez-González
AU  - Lorena Cayón-González
AU  - Paula Iruzubieta
PY  - 2026
DA  - 2026/10/22
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219407
UR  - https://www.mdpi.com/1422-0067/27/21/9407
AB  - Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic disorder in which cardiovascular, hepatic and oncological outcomes shape long-term prognosis. Statins are particularly relevant because their cardiovascular benefit is firmly established, yet they remain underused in MASLD, while their potential liver-related effects remain uncertain. Observational studies consistently associate statin exposure with slower fibrosis progression, fewer major adverse liver outcomes, lower hepatocellular carcinoma incidence and reduced liver-related mortality. However, direct randomized evidence in MASLD remains limited, and available studies differ substantially in disease stage, exposure, endpoint and follow-up. In this narrative review, we critically examine the cardiovascular, hepatic, oncological, randomized, observational, genetic and pharmacological evidence on statin therapy in MASLD. We aim to clarify the apparent discordance between evidence sources, assess whether statins may modify liver-related outcomes beyond their established cardiovascular benefit, and propose a framework for evaluating multidomain therapeutic effects. We propose outcome convergence as a framework for assessing whether a therapy can improve more than one clinically relevant disease domain while preserving independent causal evaluation of each outcome. Statins should therefore be regarded as a candidate, rather than an established, outcome-convergent therapy.
SN  - 1422-0067
ER  -