title: Hepatocellular carcinoma in noncirrhotic livers is associated with steatosis rather than steatohepatitis: potential implications for pathogenesis.
abstract: OBJECTIVE
  The risk of hepatocellular carcinoma (HCC) is increased in patients with metabolic syndrome (MS), possibly related to nonalcoholic fatty liver disease (NAFLD). As histological features of NAFLD may regress in cirrhosis, we compared steatosis versus steatohepatitis in the nontumoral liver of noncirrhotic HCC patients.
  
  
  METHODS
  A retrospective clinicopathological analysis was carried out in 91 noncirrhotic HCC patients. Patients were divided into three subgroups: that is, patients with: (1) MS without other risk factors for underlying liver disease, (2) no underlying risk factors, or (3) other risk factors (with or without MS). The NAFLD activity score (NAS) less than 3 was classified as no steatohepatitis, NAS 3-4 as borderline steatohepatitis, and NAS 5 or more as definite steatohepatitis.
  
  
  RESULTS
  Eleven (12%) patients had MS without other risk factors (group 1). In the nontumoral liver, significant steatosis (≥5% of hepatocytes) was generally present (in 10/11 patients), with mild lobular inflammation and absence of ballooning in most cases. Absence of steatohepatitis, borderline steatohepatitis, and definite steatohepatitis were found in 55, 45, and 0% of cases, respectively. In groups 2 and 3, significant steatosis was frequently present (in 16/37 and 21/43 patients, respectively). Absence of steatohepatitis, borderline steatohepatitis, and definite steatohepatitis were found in 84, 16, and 0% of cases (group 2), respectively, in 77, 23, and 0% of cases (group 3).
  
  
  CONCLUSIONS
  In noncirrhotic HCC patients, histological steatosis was frequently present, whereas overt steatohepatitis did not occur. These findings may be relevant for HCC pathogenesis in NAFLD.
authors.affiliation: aDepartment of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht bDepartment of Gastroenterology and Hepatology cDepartment of Surgery, Erasmus Medical Center, Rotterdam dDepartment of Medical Oncology eDepartment of Gastroenterology and Hepatology fDepartment of Pathology, Academic Medical Center Amsterdam, 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: 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: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult