title: Hepatocellular carcinoma in cirrhotic versus noncirrhotic livers: results from a large cohort in the Netherlands.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) usually occurs in patients with cirrhosis, but can also develop in noncirrhotic livers. In the present study we explored associated risk factors for HCC without cirrhosis and compared patient and tumor characteristics and outcomes in HCC patients with and without underlying cirrhosis.
  
  
  METHODS
  Patients with HCC diagnosed in the period 2005-2012 in five Dutch academic centers were evaluated. Patients were categorized according to the presence of cirrhosis on the basis of histology or combined radiological and laboratory features.
  
  
  RESULTS
  In total, 19% of the 1221 HCC patients had no underlying cirrhosis. Noncirrhotic HCC patients were more likely to be female and to have nonalcoholic fatty liver disease or no risk factors for underlying liver disease, and less likely to have hepatitis C virus or alcohol-related liver disease than did cirrhotic HCC patients. HCCs in noncirrhotic livers were more often unifocal (67 vs. 48%), but tumor size was significantly larger (8 vs. 4 cm). Despite the larger tumors, more patients underwent resection (50 vs. 10%) and overall survival was significantly better than in cirrhotics. In multivariate analyses, absence of cirrhosis [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.38-0.63] and presence of hepatitis B (HR 0.68, 95% CI 0.51-0.91) were independent predictors for lower mortality, whereas hepatitis C virus was associated with higher mortality (HR 1.32, 95% CI 1.01-1.65).
  
  
  CONCLUSIONS
  HCC without cirrhosis was strongly associated with female sex and presence of nonalcoholic fatty liver disease or no risk factors for underlying liver disease. In absence of cirrhosis, resections were more often performed, with better survival despite larger tumor size.
authors.affiliation: aDepartment of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht Departments of bGastroenterology and Hepatology cSurgery, Erasmus Medical Center, Rotterdam dDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden Departments of eMedical Oncology fGastroenterology and Hepatology gPathology, Academic Medical Center Amsterdam hDepartment of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Meer
authors.forename: Karel J
authors.initials: KJ
authors.lastname: van Erpecum
authors.forename: Dave
authors.initials: D
authors.lastname: Sprengers
authors.forename: Minneke J
authors.initials: MJ
authors.lastname: Coenraad
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Klümpen
authors.forename: Peter L M
authors.initials: PL
authors.lastname: Jansen
authors.forename: Jan N M
authors.initials: JN
authors.lastname: IJzermans
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.forename: Carin M J
authors.initials: CM
authors.lastname: van Nieuwkerk
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000601:surgery; D016009:Chi-Square Distribution; D002648:Child; D005260:Female; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000601:surgery; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000601:surgery; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D011237:Predictive Value of Tests; D015995:Prevalence; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult