title: Functional decline in patients with cirrhosis awaiting liver transplantation: Results from the functional assessment in liver transplantation (FrAILT) study.
abstract: Cirrhosis is characterized by sarcopenia and malnutrition, leading to progressive functional decline. We aimed to objectively measure functional decline in patients with cirrhosis awaiting liver transplantation and its association with waiting list mortality. Consecutive adults listed for liver transplantation with laboratory Model for End-Stage Liver Disease (MELD) ≥12 at a single center underwent functional status assessments at every outpatient visit using the Short Physical Performance Battery (0 = impaired to 12 = robust), consisting of gait, chair stands, and balance tests. Joint linear time-to-event analyses modeled the simultaneous impact of the longitudinal trajectory of physical function on waiting list mortality (=death or delisted for being too sick for liver transplantation). Included were 309 liver transplantation candidates. Median laboratory MELD was 15, serum albumin was 3.0 g/dL, 28% had ascites, 18% had hepatic encephalopathy, and 83% were Child class B or C. At a median follow-up of 14 months, 15% died or were delisted and 28% underwent liver transplantation. Average physical function worsened per 3 months on the waiting list: -0.38 kg in grip strength, -0.05 meters/second in gait, 0.03 seconds in chair stands, and -0.16 Short Physical Performance Battery points. In joint models of longitudinal trajectories of physical function and waiting list mortality adjusted for MELD-Na, albumin, hepatocellular carcinoma, and baseline physical function, the longitudinal trajectories of each physical function measure were significantly associated with waiting list mortality: grip (hazard ratio = 0.89, 95% confidence interval 0.83-0.95), gait (hazard ratio = 0.72, 95% confidence interval 0.62-0.84), chair stands (hazard ratio = 1.17, 95% confidence interval 1.09-1.25), and Short Physical Performance Battery <10 (hazard ratio = 1.45, 95% confidence interval 1.15-2.20).
  
  
  CONCLUSIONS
  Liver transplantation candidates experience significant functional decline on the waiting list, despite modest wait time and low baseline MELD; decline in physical function is associated with an increased risk of death or delisting, independent of liver disease severity.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Lai
authors.affiliation: Department of Surgery, Division of Transplant Surgery, University of California-San Francisco, San Francisco, CA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dodge
authors.affiliation: Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA.
authors.forename: Saunak
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Medicine, Division of Geriatrics, University of California-San Francisco, San Francisco, CA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Covinsky
authors.affiliation: Department of Surgery, Division of Transplant Surgery, University of California-San Francisco, San Francisco, CA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Feng
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014850:Waiting Lists / Q000401:mortality