title: Clinical features and outcome of cryptogenic hepatocellular carcinoma compared to those of viral and alcoholic hepatocellular carcinoma.
abstract: BACKGROUND
  Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALC-HCC) in Korea.
  
  
  METHODS
  The clinical features, treatment modalities, and survival data for 480 patients with HCC consecutively enrolled from January 2003 to June 2012 were analyzed. Computed tomography images were used to measure the visceral fat area (VFA) and liver-spleen density ratio.
  
  
  RESULTS
  Cryptogenic HCC accounted for 6.8% of all HCC cases, whereas HBV-HCC, HCV-HCC, and ALC-HCC accounted for 62.7%, 13.5%, and 10.7% of HCC cases, respectively. The cryptogenic HCC group was characterized by older age, a low proportion of male patients, a high proportion of patients with metabolic syndrome or single nodular presentation, and a low proportion of patients with portal vein invasion compared to the viral-HCC and ALC-HCC groups. However, Child Pugh classes, tumor stages, and overall survival rates of cryptogenic HCC patients were similar to those of patients with HCC of other etiologies. VFA in cryptogenic HCC patients was significantly higher than that in viral-HCC patients, but similar to that in ALC-HCC patients. The liver-spleen density ratio did not vary according to HCC etiology.
  
  
  CONCLUSIONS
  Cryptogenic HCC accounts for approximately 7% of HCC cases in Korea, associated with an older age at diagnosis, more frequent occurrence of metabolic syndrome, and less aggressive tumor characteristics, but similar survival compared to viral-HCC or ALC-HCC. Based on VFA and the liver-to-spleen density ratio, cryptogenic HCC may be burnt-out NAFLD in which visceral fat remains but liver fat is depleted.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, South Korea.
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Lee
authors.forename: Sook-Hyang
authors.initials: SH
authors.lastname: Jeong
authors.forename: Young-Sang
authors.initials: YS
authors.lastname: Byoun
authors.forename: Seong Min
authors.initials: SM
authors.lastname: Chung
authors.forename: Mun Hyuk
authors.initials: MH
authors.lastname: Seong
authors.forename: Hyung Rae
authors.initials: HR
authors.lastname: Sohn
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Min
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jang
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Guan Jung
authors.initials: GJ
authors.lastname: Park
authors.forename: Yoon Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kyoung Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Soyeon
authors.initials: S
authors.lastname: Ahn
mesh_terms: D000368:Aged; D000437:Alcoholism / Q000150:complications; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology*; D005234:Fatty Liver / Q000150:complications; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D015995:Prevalence