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Liver frailty and all-cause mortality in the older participants of the Salus in Apulia Study

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Abstract

The liver contribution to the biological network underlying physical frailty in aging is underestimated. How best to measure this contribution magnitude and impact on health risk trajectories in frail individuals is not yet entirely clear. We analyzed the association of a novel liver frailty phenotype with the risk of death in older participants of the Salus in Apulia Study cohort. Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1929 older adults (65 +). Physical frailty was classified by Cardiovascular Health Study criteria, and liver fibrosis risk by fibrosis-4 (FIB-4). The liver frailty phenotype was defined as physical frailty plus high-risk liver fibrosis (score > 2.67). Physical frailty, high-risk liver fibrosis, and liver frailty subjects were compared to subjects without these conditions (non-frail). Proportional Cox regression tested the adjusted association between liver frailty and all-cause mortality for each category. The liver frailty prevalence was relatively low (3.8%), but higher in men (58.1%). Compared to non-frail older subjects, liver frailty subjects were significantly older (effect size (ES) − 1.11, 95% confidence interval (CI) − 1.35 to − 0.87), with a lower education (ES 0.48, 95%CI 0.24 to 0.71) and higher multimorbidity (ES 15.81, 95%CI 4.20 to 27.41). Cox multivariate analyses showed a two-fold increased risk of overall mortality (hazard ratio 2.09, 95%CI 1.16–3.74) even after the adjustment for age, sex, education, and alcohol consumption. The liver frailty phenotype runs twice the risk of overall mortality compared with the non-frail population. This clinical tool, validated in a Southern Italian population, is based on simple sets of measures that can conveniently be assessed also in the primary care setting.

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Acknowledgements

We thank the “Salus in Apulia” Research Team. This manuscript is the result of the research work on frailty undertaken by the “Italia Longeva: Research Network on Aging” team, supported by the resources of the Italian Ministry of Health—Research Networks of National Health Institutes. We thank the General Practitioners of Castellana Grotte for their fundamental role in the recruitment of participants to these studies: Cecilia Olga Maria Campanella, Annamaria Daddabbo, Giosuè Dell’aera, Rosalia Francesca Giustiniano, Massimo Guzzoni Iudice, Savino Lomuscio, Rocco Lucarelli, Antonio Mazzarisi, Mariana Palumbo, Maria Teresa Persio, Rosa Vincenza Pesce, Gabriella Puzzovivo, Pasqua Maria Romano, Cinzia Sgobba, Francesco Simeone, Paola Tartaglia, and Nicola Tauro.

Funding

Italian Ministry of Health with “Ricerca Corrente 2020” funds.

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Authors and Affiliations

  1. Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis,” Research Hospital, Castellana Grotte, Bari, Italy

    Roberta Zupo, Fabio Castellana, Rossella Donghia, Luisa Lampignano, Vito Guerra, Madia Lozupone, Ilaria Bortone, Sara De Nucci, Rossella Tatoli, Sarah Tirelli, Francesco Panza & Rodolfo Sardone

  2. Unit of Geriatrics and Internal Medicine, National Institute of Gastroenterology “Saverio de Bellis,” Research Hospital, Castellana Grotte, Bari, Italy

    Giovanni De Pergola

  3. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Bari, Italy

    Giancarlo Sborgia

  4. Scientific Direction, National Institute of Gastroenterology “Saverio de Bellis,” Research Hospital, Castellana Grotte, Bari, Italy

    Gianluigi Giannelli

Authors
  1. Roberta Zupo
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  2. Fabio Castellana
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  3. Rossella Donghia
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  4. Luisa Lampignano
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  6. Giovanni De Pergola
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  7. Madia Lozupone
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  8. Ilaria Bortone
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  9. Sara De Nucci
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  10. Rossella Tatoli
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  12. Giancarlo Sborgia
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  13. Gianluigi Giannelli
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  14. Francesco Panza
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  15. Rodolfo Sardone
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Correspondence to Francesco Panza or Rodolfo Sardone.

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Zupo, R., Castellana, F., Donghia, R. et al. Liver frailty and all-cause mortality in the older participants of the Salus in Apulia Study. GeroScience 44, 835–845 (2022). https://doi.org/10.1007/s11357-021-00434-x

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  • DOI: https://doi.org/10.1007/s11357-021-00434-x

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