Close association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus-associated cirrhosis
Article first published online: 15 MAR 2002
Copyright © 2002 American Cancer Society
Volume 94, Issue 6, pages 1787–1795, 15 March 2002
How to Cite
Tarao, K., Rino, Y., Ohkawa, S., Tamai, S., Miyakawa, K., Takakura, H., Endo, O., Yoshitsugu, M., Watanabe, N. and Matsuzaki, S. (2002), Close association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus-associated cirrhosis. Cancer, 94: 1787–1795. doi: 10.1002/cncr.10391
- Issue published online: 15 MAR 2002
- Article first published online: 15 MAR 2002
- Manuscript Accepted: 29 OCT 2001
- Manuscript Revised: 23 OCT 2001
- Manuscript Received: 8 MAR 2001
- Fund for Cancer Research from the Ministry of Welfare of Japan
- Mitsui Life Social Welfare Foundation
- Japanese Foundation for Multidisciplinary Treatment of Cancer
- Viral Hepatitis Research Foundation of Japan
- multicentric carcinogenesis;
- hepatocellular carcinoma;
- alanine aminotransferase;
- hepatitis C virus-associated cirrhosis;
- chronic inflammation
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.
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 (≥ 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 > 5years. 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.
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.
These results showed a close correlation between multicentric hepatocarcinogenesis and sustained necroinflammation of the liver in patients with HCV-LC. Cancer 2002;94:1787–95. © 2002 American Cancer Society.