Frailty and Sarcopenia in Cirrhosis

Abstract

Originally described in the field of geriatrics, frailty is a syndrome of “decreased physiologic reserve” which leads to progressive disability and a decreased ability to adapt to stressors. Frailty is associated with declines across multiple organ systems (e.g. skeletal muscle loss, immune dysfunction), and increased risk of hospitalization, disability, and death. Although frailty was originally associated with aging, it is now known to be prevalent in chronic diseases such as renal failure and cirrhosis. Sarcopenia is characterized by a progressive generalized loss of skeletal muscle mass and may be thought of as a precursor or subdomain of the broader functional decline seen in patients with frailty. Although the pathophysiology of frailty and sarcopenia is incompletely understood, hyperammonemia and myostatin upregulation are thought to play a key role in skeletal muscle loss. The prevalence of frailty (17–49%) and sarcopenia (22–70%) varies across studies depending on the measures and diagnostic thresholds used.

A variety of clinical tools have been developed to measure frailty and sarcopenia in patients with cirrhosis. Some commonly studied tools include the Karnofsky Performance Status (KPS), Fried Frailty Index (FFI), Liver Frailty Index (LFI), and CT muscle mass measurements. Each measure has its pros and cons, and more research studies are needed to compare their predictive value. Regardless of measurement methodology, frailty, and sarcopenia are associated with a roughly twofold increased risk of mortality in patients with cirrhosis. The association is slightly attenuated but remains significant after adjusting for MELD score. This is especially important to consider when evaluating patients with cirrhosis for transplant as the combination of MELD and frailty scores is a superior predictor of waitlist mortality than MELD scores alone. Going forward, exercise programs and pharmacologic interventions targeting frailty and sarcopenia are being studied to improve outcomes in cirrhosis and transplant. However, as expressed in a recent expert opinion statement by the American Society of Transplantation (AST), “there is no single frailty tool that has emerged in the literature as suitable for evaluation of patients with cirrhosis in all clinical scenarios (outpatient vs. inpatient; transplant vs. nontransplant).” Therefore, a nationally standardized process for assessing frailty and/or sarcopenia is needed for these valuable metrics to be incorporated into the management of patients with cirrhosis.