A STUDY ON INFLUENCE OF FIBROSIS, INFLAMMATION AND HBV GENOTYPES

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DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN CHRONIC TYPE B LIVER DISEASES: A STUDY ON INFLUENCE OF FIBROSIS, INFLAMMATION AND HBV GENOTYPES -abstract 806 Hajime Sumi, Fumio Imazeki, Osamu Yokosuka, Tomoko Kurihara, Takaaki Imamura, Tatsuo Kanda, Keni chi Fukai, Hiromitsu Saisho, Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan Epidemiological studies have demonstrated a strong relationship between hepatocellular carcinoma (HCC) and chronic hepatitis B virus (HBV) infection. Several factors such as cirrhosis are reported to play roles in hepatocarcinogenesis. The importance of liver inflammation in the development of HCC was demonstrated in a mouse model with liver inflammation. HBV genotype also suggested to be correlated with the clinical features of HBV infection. On the other hand, recent molecular biological studies have revealed the oncogenic potential of the HBV virus itself, suggesting that the mere infection of HBV may be a risk factor for the development of HCC. This study was performed to elucidate the roles of hepatic inflammation, existence of cirrhosis and HBV genotype in the development of HCC. The subjects were 332 consecutive patients with chronic HBV infection who were followed for at least 2 years at the First Department of Internal Medicine, Chiba University Hospital. Liver function tests were performed al least every 3 months and ultrasonography was performed every 6-12 months. Patients whose serum alanine aminotransferase (ALT) level remained within the normal range during at least the last 2 years of follow-up were defined as having a sustained normal ALT level. The diagnosis of cirrhosis was made based on either the finding of cirrhosis on biopsy, or the presence of the typical ultrasonographic findings suggestive of cirrhosis and evidence of portal hypertension. The HBV genotype was determined using the patients' sera with commercial kit (Tokushu-Meneki Laboratory, Tokyo, Japan). The diagnosis of HCC was made by liver biopsy or imaging studies. The results of this study showed that of the 332 patients in this study (207 (62.3%) men and 125 (37.7%) women, with a mean age of 36.0 ?13.2). 43 (12.9%) had cirrhosis and 289 (87.1%) had chronic hepatitis without cirrhosis. The distribution of HBV genotypes was: A in 7 (2.1%), B in 40(12.0%) and C in 285 (85.9%) patients. None of the patients had genotype D, E, or F. Sustained normalization of the ALT level during the last 2 years of follow-up was observed in 121 patients (36.4%). During a mean follow-up period of 8.6?5.0 (S.D.) years, HCC developed in 34 cases (10.2%). HCC developed in 23(8.0%) of the 289 originally non-cirrhotic patients with a yearly incidence of 1.0% and in 11 (25.6%) of the 43 cirrhotic patients with a yearly incidence of 2.9% (p<0.001) HCC developed in 6/121 (5.0%) patients with sustained ALT normalization and in 27/211 (12.8%) without sustained ALT normalization (p<0.022). With regard to HBV genotype-- (10.0%) of 40 patients with genotype B, and 30 (10.5%) of 285 patients with genotype C developed HCC (p: not significant), with a yearly incidence of 1.1% and 1.2%, respectively. None of the 7 patients with genotype A developed HCC. Of the 34 patients who developed HCC, 14 (41.1%) had a non-cirrhotic liver and 20 (58.9%) had a cirrhotic liver at the time of developing HCC. 5 (14.6 %) of the 34 patients with HCC had both a sustained normal ALT level and a non-cirrhotic liver when HCC was found. The authors of this study concluded that a significant proportion of the HCC cases had developed in non-cirrhotic patients with sustained ALT normalizalion, suggesting the strong carcinogenic potential of HBV itself. The HBV genotype seems to have limited influence on the development of HCC, while liver cirrhosis and inflammation as manifested by the serum ALT level were additional risk factors for the development of HCC. (hepatitis-b-mail)