title: Hepatocellular Carcinoma Is the Most Common Indication for Liver Transplantation and Placement on the Waitlist in the United States.
abstract: OBJECTIVE
  Management strategies for patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) have changed, along with liver allocation policies based on model for end-stage liver disease score. We investigated etiologic-specific trends in liver transplantation in the United States during different time periods.
  
  
  METHODS
  We performed a retrospective study, using the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry data, to identify all adult patients registered for liver transplantation in the United States from January 1, 2004, through December 31, 2015. For subjects listed with multiple diagnoses, HCC was considered the primary listing diagnosis. To determine whether availability of direct-acting antiviral agents, which began in 2011, affected pretransplant (death or drop-out) and post-transplant outcomes for patients with HCV infection, we compared data from the time periods of 2004 to 2010 and 2011 to 2014. We used competing-risk analysis to compare differences in end points between these periods. Differences between periods in pretransplantation and post-transplantation outcomes were estimated using Kaplan-Maier analysis and compared using the log-rank test. Associations between year of listing and pre-liver transplant outcome, and year of liver transplant and survival after transplant, were examined using the log-rank test. Proportional hazard regression was used to evaluate the reliability of the time period effect with potential confounders.
  
  
  RESULTS
  Among 109,018 registrants, 18.5% were registered for liver transplantation because of HCC. In 2015, HCC was the leading diagnosis among registrants (23.9% of registrations) and recipients (27.2% of recipients). Between 2004 and 2015, the ratio of registrants with vs without HCC increased 5.6-fold for patients with HCV infection, 1.9-fold for patients with hepatitis B virus (HBV) infection, 2.7-fold for patients with alcohol abuse, and 10.2-fold for patients with nonalcoholic steatohepatitis. After adjusting for covariates, we associated the period of 2011 to 2014 with a decreased probability that HCC registrants would undergo liver transplantation (hazard ratio [HR], 0.62; P < .0001). The period of 2011 to 2014 also was associated with a decreased probability of drop-out owing to deterioration or death from HCV-induced (HR, 0.90; P = .0003), HBV-induced (HR, 0.71; P = .002), or alcohol-induced (HR, 0.90; P = .01) liver disease, and an increased probability of delisting as a result of clinical improvement in patients with HCV infection (HR, 3.4; P < .0001), HBV infection (HR, 2.3; P = .004), or alcohol abuse (HR, 2.2; P < .0001). The period of 2011 to 2014 was associated with a decreased risk of graft loss or death, with the largest effect seen in HCV-infected recipients (HR, 0.76; P < .0001).
  
  
  CONCLUSIONS
  HCC was the leading indication for liver transplantation in the United States in 2015. Despite this, the probability of liver transplantation decreased the most in registrants with HCC. Pretransplantation and post-transplantation outcomes have improved, particularly in patients with HCV infection.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Ju Dong
authors.initials: JD
authors.lastname: Yang
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Larson
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Kymberly D
authors.initials: KD
authors.lastname: Watt
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Alina M
authors.initials: AM
authors.lastname: Allen
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Russell H
authors.initials: RH
authors.lastname: Wiesner
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Roberts
authors.affiliation: Division of Transplant Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Heimbach
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota. Electronic address: Leise.Michael@mayo.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Leise
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000601:surgery*; D006801:Humans; D017093:Liver Failure / Q000209:etiology* / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D014850:Waiting Lists; D055815:Young Adult
keywords: Database; LT; Liver Cancer; UNOS/OPTN