Functional capacity in cirrhosis is predicted by additive impact of covert hepatic encephalopathy and frailty in a multi-center outpatient cohort

ABSTRACT

Background: Daily functional capacity is a major determinant of outcomes in patients with chronic medical conditions. Given that it can be affected by disease-specific factors as well as physical and cognitive impairment, it may be of increasing relevance in patients with cirrhosis given the changing demographics and increasing co-existing conditions including HE and physical frailty. An integrated multi-site approach combining cirrhosis-related factors, comorbidities, cognitive function, and frailty metrics is needed. Aim: To determine the integrated effect of frailty and CHE on functional capacity in outpatients with cirrhosis. Methods: NACSELD-3 (North American Consortium for the Study of End-Stage Liver Disease) is a new cohort of outpatients with cirrhosis recruited from 11 centers across North America. We enrolled pts able to consent, without HIV/illicit drug use or current alcohol misuse. Demographics, cirrhosis severity/history, comorbidities, medications were recorded. DASI (Duke Activity Status Index, Low=worse), studies that assess functional capacity, Liver frailty index instruments (LFI, high=worse) & EncephalApp Stroop (High time=worse) were administered. Norms were used to classify pts as having CHE on EncephalApp & frailty on LFI. Pts divided into having none, either or both CHE & frailty. Regression analyses were performed for DASI using all clinical variables collected. Results: Demographics 220 patients (61.7±10.6 yrs, 74% men, 76% White, 6% Latinx) were enrolled;EncephalApp & LFI were complete in 182 pts (redgreen color blindness, logistic issues or COVID restrictions) Cirrhosis details Major etiologies were 37% alcohol, 26% NAFLD, 17% HCV and 10% HCV+alcohol. Mean MELD was 13.9±8.5, 36% had prior HE, and 19% had difficult to control ascites. Mean Charlson comorbidity index was 5.1±2.2 Cognition, frailty and DASI EncephalApp total was 184.2±55.6 seconds and 148 (64%) pts had CHE. Mean LFI score was 3.89±0.63 and 37 (16%) were deemed frail. 49 (27%) had neither CHE nor frailty, 104 (58%) had either CHE or Frailty , and 26 (15%) had both (Fig A). EncephalApp & LFI were positively correlated (r=0.36, p<0.001) and both were correlated with DASI (EncephalApp r=-0.33, LFI r=-0.27, both p<0.001). DASI was lower with both CHE & Frailty (Fig B). Regression Variables associated with lower DASI (poor capacity) were higher MELD score (T-value -2.1, p=0.03), higher CCI (T-value -3.6, p<0.0001) and being frail+CHE versus either or none (T-value -2.6, p=0.01). No interaction between LFI and EncephalApp was seen. Conclusion: In this multi-center experience combined frailty and covert hepatic encephalopathy and cirrhosis-unrelated comorbidities significantly add to MELD score in predicting functional capacity in outpatients with cirrhosis.