title: Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S.
  
  
  METHODS
  We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features.
  
  
  RESULTS
  A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC.
  
  
  CONCLUSIONS
  Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis.
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas. Electronic address: smittal@bcm.edu.
authors.forename: Sahil
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas; Sections of Health Services Research, Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Hashem B
authors.initials: HB
authors.lastname: El-Serag
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas.
authors.forename: Yvonne H
authors.initials: YH
authors.lastname: Sada
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas; Sections of Health Services Research, Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Fasiha
authors.initials: F
authors.lastname: Kanwal
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Sections of Health Services Research, Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Sections of Health Services Research, Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Sarah
authors.initials: S
authors.lastname: Temple
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Sections of Health Services Research, Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: May
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Sections of Health Services Research, Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Kramer
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Sections of Health Services Research, Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Richardson
authors.affiliation: Center of Innovation, Effectiveness and Quality, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Sections of Health Services Research, Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Davila
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014728:Veterans
keywords: Fatty Liver; Liver Cancer; NASH; Steatosis