title: Close association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus-associated cirrhosis.
abstract: BACKGROUND
  Multicentric development of hepatocellular carcinoma (HCC) is a characteristic feature of hepatitis C virus (HCV)-associated cirrhosis (HCV-LC). In this study, the objective was to determine whether the persistent elevation of the serum alanine aminotransferase (ALT) level, which represents the inflammatory necrosis of hepatocytes, is correlated with the multicentric development of hepatocellular carcinoma (HCC) in patients with early-stage HCV-LC.
  
  
  METHODS
  Ninety-three consecutive patients with biopsy proven HCV-LC (Child Stage A) who had been followed for > 5 years for the development of HCC were studied. They were subdivided into three groups according to their serum ALT level: Group A included 33 patients with annual average serum ALT levels that were persistently high (> or = 80 IU; high ALT group), Group B included 41 patients with annual average serum ALT levels that were persistently low (< 80 IU; low ALT group), and Group C included 19 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography (CT) scans for > 5 years. When the development of HCC was suspected, angiography, infusion of lipiodol into the hepatic artery, and lipiodol-CT scans were performed in all patients to determine the number of HCC nodules.
  
  
  RESULTS
  In Group A, 27 patients (81.8%) developed HCC. Seventeen of 27 patients (63.0%) had multiple nodules. In contrast, in Group B, only 12 patients (29.3%) developed HCC, and only 1 of these 12 patients (8.3%) had multiple nodules. There was a significant difference between Groups A and B in the incidence of developing HCC (P < 0.001) and developing multiple nodules (P = 0.006). In addition, among the male patients, the incidence of developing multiple HCC nodules in Group A (12 of 19 patients; 63.2%) was significantly higher (P < 0.05) compared with the incidence in Group B (0 of 6 patients; 0%). The same tendency was observed among the female patients.
  
  
  CONCLUSIONS
  These results showed a close correlation between multicentric hepatocarcinogenesis and sustained necroinflammation of the liver in patients with HCV-LC.
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tarao
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Rino
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohkawa
authors.forename: Setsuo
authors.initials: S
authors.lastname: Tamai
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyakawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Takakura
authors.forename: Osamu
authors.initials: O
authors.lastname: Endo
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Yoshitsugu
authors.forename: Norihito
authors.initials: N
authors.lastname: Watanabe
authors.forename: Shohei
authors.initials: S
authors.lastname: Matsuzaki
mesh_terms: D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications* / Q000821:virology*; D008113:Liver Neoplasms / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D000410:Alanine Transaminase