title: Irregular regeneration of hepatocytes and risk of hepatocellular carcinoma in chronic hepatitis and cirrhosis with hepatitis-C-virus infection.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) commonly develops in patients with chronic hepatitis or cirrhosis of the liver caused by hepatitis-C-virus (HCV) infection. We prospectively studied whether irregular regeneration of hepatocytes is a risk factor for HCC in these patients.
  
  
  METHODS
  242 patients were enrolled after liver biopsy and followed up by ultrasonographic scanning every 3 months. We examined age, sex, platelet count, the diagnosis of cirrhosis or chronic hepatitis, liver-cell dysplasia, and irregular regeneration. We classified irregular regeneration as slight or severe, based on histological expression of pleiomorphism, anisocytosis, bulging, and map-like distribution of hepatocytes.
  
  
  RESULTS
  37 of 63 patients with cirrhosis and 26 of 179 with chronic hepatitis were judged to have severe irregular regeneration. HCC was diagnosed in 33 of 63 patients with cirrhosis (29 had severe irregular regeneration) and 12 of 179 patients with chronic hepatitis (11 had severe irregular regeneration) during mean follow-up of 5.5 years (SD 4.1; range 1-16). Multivariate analysis with a proportional-hazards model showed severe irregular regeneration (relative risk 15.1 [95% CI 5.6-40.7], p<0.0001) and a diagnosis of cirrhosis (3.8 [1.7-8.2], p=0.0008) to be significant risk factors for HCC. Within the diagnostic categories, irregular regeneration was also significant (cirrhosis 6.8 [2.1-21.9], p=0.0014; chronic hepatitis 28.5 [2.9-276.4], p=0.0038).
  
  
  CONCLUSIONS
  We recommend that liver biopsy to look for irregular regeneration should be done in patients with HCV-related chronic liver diseases. Those with severe irregular regeneration should be followed up carefully.
authors.affiliation: Department of Medicine, Kawasaki Chuo Hospital, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: T
authors.initials: T
authors.lastname: Morizane
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: T
authors.initials: T
authors.lastname: Yamagami
authors.forename: Y
authors.initials: Y
authors.lastname: Onozuka
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: K
authors.initials: K
authors.lastname: Mitamura
authors.forename: Y
authors.initials: Y
authors.lastname: Ueno
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000209:etiology*; D008115:Liver Regeneration; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors