ABSTRACT
Liver transplantation (LT) represents a curative avenue for individuals with advanced chronic liver disease. Given the inherent illness severity of LT candidates, identifying patients at greater risk for adverse outcomes before and after transplantation is paramount. Approximately 50% of cirrhotic patients are frail and have considerable functional impairment. Various measures have been used to assess frailty, including performance-based tests and functional status evaluations. Frailty carries significant prognostic implications and predicts both mortality and pre- and post-LT complications. Contributing factors to frailty in this population include sarcopenia, malnutrition, inflammation, and psychosocial factors. Recognizing the prevalence of frailty among LT candidates, exercise interventions have been developed to improve physical frailty and offer potential to improve patient outcomes. While many interventions have demonstrated efficacy without notable adverse events, the absence of a universally accepted standard for exercise prescription underscores the variability in intervention elements and patient adherence. Given the safety profile of exercise interventions, there remains a critical need for standardized protocols and guidelines to optimize exercise regimens for LT candidates. This review delves into the landscape of frailty among LT candidates, elucidating its etiological underpinnings, impact on outcomes, utilization of exercise interventions, and the efficacy of exercise programs in reducing the burden frailty in those awaiting LT.
ABSTRACT
BACKGROUND AND AIMS: Exercise training is recommended for all patients with metabolic dysfunction-associated steatotic liver disease and may reverse liver fibrosis. Whether exercise training improves liver fibrosis without body weight loss remains controversial. We further investigated this relationship using serum biomarkers of liver fibroinflammation in a post hoc analysis of an exercise trial where patients did not lose significant body weight. METHODS: In the NASHFit trial, patients with metabolic dysfunction-associated steatohepatitis were randomized to receive either moderate-intensity aerobic exercise training or standard clinical care for 20 weeks. Mediterranean-informed dietary counselling was provided to each group. Change in serum biomarkers was measured and compared between the two groups. RESULTS: Exercise training led to improvement in serum biomarkers of liver fibroinflammation, including (1) ≥17 IU/L reduction in alanine aminotransferase (ALT) in 53% of individuals in the exercise training group compared to 13% in the standard clinical care group (p < 0.001; mean reduction 24% vs. 10% respectively) and (2) improvement in CK18 (-61 vs. +71 ng/mL, p = 0.040). ALT improvement ≥17 IU/L was correlated with ≥30% relative reduction in magnetic resonance imaging-measured liver fat and PNPLA3 genotype. CONCLUSION: Exercise training improves multiple serum biomarkers of liver fibroinflammation at clinically significant thresholds of response without body weight loss. This study provides further evidence that exercise training should be viewed as a weight-neutral intervention for which response to intervention can be readily monitored with widely available non-invasive biomarkers that can be applied at the population level.
