Exercise and physical activity in cirrhosis: opportunities or perils

Reduced exercise capacity and impaired physical performance are observed in nearly all patients with liver cirrhosis. Physical activity and exercise are physiological anabolic stimuli that can reverse dysregulated protein homeostasis or proteostasis and potentially increase muscle mass and contractile function in healthy subjects. Cirrhosis is a state of anabolic resistance, and unlike the beneficial responses to exercise reported in physiological states, there are few systematic studies evaluating the response to exercise in cirrhosis. Hyperammonemia is a mediator of the liver-muscle axis with net skeletal muscle ammonia uptake in cirrhosis causing signaling perturbations, mitochondrial dysfunction with decreased ATP content, modifications of contractile proteins, and impaired ribosomal function, all of which contribute to anabolic resistance in cirrhosis and have the potential to impair the beneficial responses to exercise. English language-publications in peer-reviewed journals that specifically evaluated the impact of exercise in cirrhosis were reviewed. Most studies evaluated responses to endurance exercise, and readouts included peak or maximum oxygen utilization, grip strength, and functional capacity. Endurance exercise for up to 12 wk is clinically tolerated in well-compensated cirrhosis. Data on the safety of resistance exercise are conflicting. Nutritional supplements enhance the benefits of exercise in healthy subjects but have not been evaluated in cirrhosis. Whether the beneficial physiological responses with endurance exercise and increase in muscle mass with resistance exercise that occur in healthy subjects also occur in cirrhotics is not known. Specific organ-system responses, changes in body composition, or improved long-term clinical outcomes with exercise in cirrhosis need evaluation.