Further Histological Study of the Role of Hepatitis B Infection on the Development of Hepatocellular Carcinoma

1964年から1980年における長崎大学での剖検例6339例のうち,肝疾患を主病変とする症例953例について,検討した.全剖検例に占める肝疾患の比率は,萎縮性肝硬変(7.7%),肝細胞癌(4.8%)で,同期間における全日本の平均(日本剖検輯報による)の5.2%及び3.5%と比較し高率であり,統計学的に有意差を示した.又,488例の萎縮性肝硬変のうち242例(49.6%)に,肝細胞癌の合併がみられ,一方303例の肝細胞癌のうち242例(78.9%)に萎縮性肝硬変が認められた.上記953例のうち,組織学的に詳細な検討が可能であった652例につき, H. E染色,志方によるオルセイン染色を行い,肝組織型,組織HBs-Agの有無,間質炎症反応の有無, Dysplasiaの有無,肝細胞癌のGrade,及びこれらの相互の関係について検討した.肝組織HBs-Agは,萎縮性肝硬変+肝細胞癌の群では高率で60.6%に陽性であった. 196例の肝細胞癌のうち,非癌部の組織が萎縮性肝硬変でないものは41例でこのうちの14例にHBs-Agが認められた.この14例のうち6例は非癌部の組織が軽度の線維かのみか,又は特に著変を認めないものであり, HBs-Agは直接にoncogenic作用を持つという仮説を支技する所見と思われた.萎縮性肝硬変症例についてLiver cell dysplasiaの有無について検討したが,肝細胞癌の合併の有無により,陽性率に差がみられた.さらに,長与B型の萎縮性肝硬変群では, HBs-Agの陽性率とDysplasiaの出現との間に有意な関係がみられた.A total of 953 cases of various types of liver diseases were selected for examination from 6339 autopsies performed in Nagasaki University Hospital from 1964 through 1980. The association between HBs-Ag in liver tissue and the histology of the liver was studied using Shikata's orcein staining method. Of the 6339 autopsies performed, 488 cases of atrophic liver cirrhosis (7.7%) and 303 cases of primary hepatocellular carcinoma (4.8%) were identified. These incidences of liver diseases were statistically significantly higher compared with those of national averages of Japan (5.2% and 3.5% respectively). A histological analysis of 953 cases indicated that 242 out of 488 cases of atrophic liver cirrhosis were associated with hepatocellular carcinoma (49.6%) and that 242 out of 303 cases of hepatocellular carcinoma were combined with atrophic liver cirrhosis (78.9%). No HBs-Ag was detected in the tissues of cases of acute liver atrophy or liver cirrhosis with the exception of atrophic liver cirrhosis. HBs-Ag was present in 6 out of 22 cases of subacute hepatitis (27.2%) and in 6 out of 37 chronic hepatitis (16.2%). The highest rate of detectable HBs-Ag was observed in the liver tissues of the subgroup of atrophic liver cirrhosis with hepatocellular carcinoma (60.6%). Among 196 cases of hepatocellular carcinoma examined, HBs-Ag was detected in 14 of those cases which did not exhibit atrophic liver cirrhosis. These results suggest that nepatocellular carcinoma can arise without setting of hepatitis B chronic liver cirrhosis and support the hypothesis that HBs-Ag may be directly oncogenic. Liver cell dysplasia was found in 69 out of 154 cases of atrophic liver cirrhosis with hepatocellular carcinoma (44.8%) and in 22 out of 122 cases of atrophic liver cirrhosis without hapatocellular carcinoma (18.0%). Furthermore, there was a strong correlation between the presence of HBs-Ag in the liver tissue of Nagayo's type B atrophic liver cirrhosis and the existence of cellular dysplasia