Liver transplantation in the patient with physical frailty

Frailty is a decline in functional reserve across multiple physiological systems. A key component of frailty is sarcopenia, which denotes a loss of skeletal muscle mass and impaired contractile function that ultimately result in physical frailty. Physical frailty/sarcopenia are frequent and contribute to adverse clinical outcomes before and after liver transplantation. Frailty indices, including the liver frailty index, focus on contractile dysfunction (physical frailty), while cross-sectional image analysis of muscle area is the most accepted and reproducible measure to define sarcopenia. Thus, physical frailty and sarcopenia are interrelated. The prevalence of physical frailty/sarcopenia is high in liver transplant candidates and these conditions have been shown to adversely impact clinical outcomes including mortality, hospitalisations, infections, and cost of care both before and after transplantation. Data on the prevalence of frailty/sarcopenia and their sex- and age-dependent impact on outcomes are not consistent in patients on the liver transplant waitlist. Physical frailty and sarcopenic obesity are frequent in the obese patient with cirrhosis, and adversely affect outcomes after liver transplantation. Nutritional interventions and physical activity remain the mainstay of management before and after transplantation, despite limited data from large scale trials. In addition to physical frailty, there is recognition that a global evaluation including a multidisciplinary approach to other components of frailty (e.g., cognition, emotional, psychosocial) also need to be addressed in patients on the transplant waitlist. Recent advances in our understanding of the underlying mechanisms of sarcopenia and contractile dysfunction have helped identify novel therapeutic targets.