FRAILTY is a complex clinical syndrome characterised by reduced homeostasis, lower reserve capacity, and impaired resistance to stress, increasing the risk of adverse health outcomes, including disability, hospitalisation, and early mortality. Although initially linked to older populations, frailty is now also recognised as associated with chronic diseases such as cirrhosis and advanced chronic liver disease (ACLD), independently of age. Recent research highlights frailty as a critical prognostic factor linked to mortality, healthcare needs, and reduced quality of life among ACLD patients.
Frailty has emerged as a therapeutic target in ACLD management, with non-pharmacological interventions showing promise. Strategies such as structured exercise, nutritional changes, branched-chain amino acid supplementation, multistrain probiotics, and mineral-rich, low sodium water have all demonstrated potential benefits. Studies show that these interventions can improve frailty, reduce falls, and lower emergency room consultations. Moreover, multifactorial interventions combining home exercise, branched-chain amino acids, and probiotics have been shown to positively affect frailty, physical function, and related clinical outcomes.
Biomarkers linked to frailty are of growing interest, as they can enhance the understanding of the underlying physiological mechanisms and suggest new therapeutic approaches. Evidence suggests that systemic inflammation, bacterial translocation, and disrupted metabolism are key factors associated with frailty progression. Key biomarkers such as sCD163 (a macrophage activation marker) and LBP (a bacterial translocation index) have shown correlations with frailty, supporting the idea that systemic inflammation and gut dysbiosis play a role in disease progression. Furthermore, mitochondrial dysfunction and metabolic changes – evident through levels of amino acids, short-chain fatty acids, and other metabolic markers – further elucidate frailty’s multifaceted nature.
This research highlights the complex interplay between inflammation, bacterial translocation, metabolism, and frailty. Importantly, the multifactorial interventions in ACLD patients improved both clinical biomarkers and frailty, supporting the therapeutic value of lifestyle and dietary modifications. Although findings are promising, further studies are needed to confirm these mechanisms and evaluate the effects in broader populations and advanced liver disease stages. Nonetheless, this evidence emphasises that non-pharmacological interventions could play a pivotal role in improving frailty and overall patient outcomes in ACLD.
Katie Wright, EMJ
Reference
Laghi L et al. Biomarkers of frailty in patients with advanced chronic liver disease undergoing a multifactorial intervention consisting of home exercise, branched-chain amino acids, and probiotics. Biomolecules. 2024;14(11):1410.
