Stage of Cirrhosis Predicts Risk of Liver Related Death in Low MELD Patients with Cirrhosis Awaiting Liver Transplant Manuscript ID LT-14-001.R1 Stage of Cirrhosis Predicts Risk of Liver Related Death in Low MELD Patients with Cirrhosis Awaiting Liver Transplant Joel Wedd1, Kiran M. Bambha1, Matt Stotts2, Heather Laskey1, Jordi Colmenero1,3, Jane Gralla4, Scott W. Biggins1 Affiliations: 1University of Colorado Denver Division of Gastroenterology and Hepatology. 2 Saint Louis University Division of Gastroenterology and Hepatology. 3Liver Transplant Unit, Hospital Clinic, Institut D’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona. 4 University of Colorado Denver Departments of Pediatrics and Biostatistics and Informatics. Contact information: Scott W. Biggins, MD, MAS Hepatology and Liver Transplantation University of Colorado Denver, Aurora CO Anschutz Outpatient Pavilion 7th floor 1635 Aurora Ct Mail Stop B-154 Aurora, CO 80045 Phone (720) 848-2293 Fax (303) 724-1891 [email protected] The authors have no conflicts of interest to disclose. This work was funded in part by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK076565) and from Agency for Healthcare Research and Quality (DK076565) to S.W.B. and from the National Institute of Health (5T32DK07038) to J.P.W. J.C was supported by a Dr. Juan Rodes Grant from the Spanish Association for the Study of the Liver (AEEH). Running Title: Cirrhosis stage and death in low MELD patients Keywords: liver transplantation, waitlist mortality, MELD, clinical outcomes, cirrhosis Abbreviations: LT, Liver transplant; Word Count Abstract: 275 Character Count Title (with spaces): 117 Word Count (including abstract, body, references, legend figures and tables): 5,522 Working title: Stage of Cirrhosis Predicts Risk of Liver Related Death in Low MELD Patients with Cirrhosis Awaiting Liver Transplant

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Liver Transplantation

Stage of Cirrhosis Predicts Risk of Liver Related Death in Low MELD Patients with Cirrhosis Awaiting Liver Transplant

Abstract MELD has reduced predictive ability in cirrhotic patients with MELD ≤ 20. We aimed to assess whether a 5-stage clinical model identifies liver transplant (LT) candidates with low MELD who are at increased risk for death. We conducted a case-control study of cirrhotic subjects with MELD ≤ 20 awaiting LT at a single academic medical center from 2/2002-5/2011. Conditional logistic regression was used to evaluate the risk of liver-related death based on cirrhosis stage. We identified 41 case subjects who died from liver-related causes with a MELD ≤ 20 within 90 days of death while waiting for LT. Cases were matched with up to 3 controls, totaling 66 controls, based on listing year, age, gender, liver disease etiology, hepatocellular carcinoma, and MELD. Cirrhosis stage (1=no varices or ascites, 2=varices, 3=variceal bleed, 4=ascites, 5=ascites and variceal bleed) was assessed for all subjects. MELD scores were similar for cases and controls. Clinical states contributing to death in cases were: sepsis 48%, spontaneous bacterial peritonitis 42%, variceal bleeding 24%, and hepatorenal syndrome 21%. In univariate analyses, variceal bleed (OR 5.6, p= 0.003), albumin (OR 0.5, p=0.041), increasing cirrhosis stage (p=0.003) and reaching stage 2, 3, or 4 cirrhosis versus lower stages (OR 3.6, p=0.048; OR 7.4, p