Interactions Between Sarcopenia, Physical Frailty and Resting Energy Expenditure in Cirrhosis and Portal Hypertension

<b>Background/Objectives:</b> Sarcopenia and frailty are prevalent and independently prognostic in cirrhosis. Few studies have evaluated both together to ascertain their interaction and phenotypic differences. None have studied their relationship with resting energy expenditure (REE). We simultaneously examined sarcopenia, frailty and REE in a cohort of patients with cirrhosis and portal hypertension-a novel approach. <b>Methods:</b> We retrospectively studied consecutive patients with cirrhosis and portal hypertension, prospectively recruited between 2015 and 2018 to undergo sarcopenia (transversal psoas muscle thickness [TPMT]/height), frailty (Fried Frailty Index [FFI]), and REE assessments via indirect calorimetry. The primary outcome was transplant-free survival (TFS). <b>Results:</b> Ninety-seven patients were recruited with sarcopenia and frailty present in 26% and 40%, respectively. Patients with sarcopenia or frailty alone were phenotypically similar except those with sarcopenia had lower median body mass index (BMI) (23 vs. 28 kg/m², <i>p</i> = 0.032) and were more likely to be hypermetabolic (60% vs. 0%, <i>p</i> = 0.017). Median TFS was lower in patients with sarcopenia (3.6 months) or frailty (4.5 months), compared to those with neither (10.3 months), while patients with both sarcopenia and frailty exhibited the worst TFS (1.8 months, log-rank <i>p</i> = 0.001). Independent predictors of death or liver transplant were sarcopenia, hepatic encephalopathy, and a higher model for end-stage liver disease score. <b>Conclusions:</b> In patients with cirrhosis and portal hypertension, sarcopenia and physical frailty are related but have differences in BMI and REE. The deleterious impact of sarcopenia and frailty on TFS are additive. Sarcopenia remains an independent predictor of TFS after adjusting for frailty.