HEPATITIS B SURFACE ANTIGEN IN CIRRHOSIS OF THE LIVER AND PRIMARY LIVER CARCINOMA IN NAGASAKI AREA: A HISTOPATHOLOGICAL STUDY

肝硬変は広く世界中に分布しているが、地域により発生頻度が異なる(宮地, 1972)。肝癌も世界中に広く発生をみるが、その分布および頻度は肝硬変とは必ずしも一致せず(宮地, 1972)、地理病理学的ならびに成因論的に注目されている。わが国においても肝硬変の発生頻度は地域により異なり、九州・四国地方に多発すると言われている(松下・重松, 1972)。そして肝癌の多発地域においてもほぼ同様のことが言える(松下・重松, 1972)。長崎地方は肝硬変・肝癌の多発地域として知られており(松隅, 1967；高岡ら, 1971)、その多発性の要因ならびに原因として、マイコトキシン、アルコールあるいは肝炎ウイルスの関与などが考えられて来た。長崎地方の肝硬変・肝癌とマイコトキシンやアルコールとの関係に関する研究はかなり広範囲かつ精力的に行われているが、まだその因果関係についての結論は得られていない(松隅, 1967；高岡ら, 1971；倉田, 1972；斎藤ら, 1977)。最近、肝炎ウイルス、とくにB型肝炎ウイルスは慢性肝疾患、肝癌の成因として、重要な病因因子として多くの注目をあびつつある(Hadziyannis et al., 1970; Sherlock et al., 1970; 織田, 1975)。著者は長崎大学で剖検された肝硬変・肝癌およびそれらの関連疾患を含めて、B型肝炎ウイルスとこれらの肝疾患との関連性について、B型肝炎ウイルスの表層抗原（以下 HBs-Agと記す）を、志方らのオイルセイン法（志方ら、1973；Shikata et al.,1974）を用いて調べ、それぞれの肝疾患におけるHBs-Ag陽性率を比較検討し、それらの各疾患の成立、進展にHBs-Agがどのような関与を示しているかを明らかにすべく、この研究を行った。得られた成績について2、3の検討を行ったので、その概要を報告する。The annual of pathological autopsy cases in Japan indicate that out of 4,760 autopsy cases at Nagasaki University during the period 1964 to 1973, 445 (9.3%) are cirrhosis of the liver and 240 (5.0%) are primary liver carcinoma (PLC), and that 392 (88.1%) of 445 cirrhosis are atrophic liver cirrhosis and 180 (45.9%) of 392 atrophic liver cirrhosis are accompanied with hepatocellular carcinoma and 218 (90.8%) of 240 PLC are hepatocellular carcinoma. The data show that atrophic liver cirrhosis and hepatocellular carcinoma are relatively higher in incidence in Nagasaki area than other parts of Japan as has been suggested before. Hepatitis B surface Antigen (HBs-Ag) of 353 sutopsy cases of liver diseases during the same period, especially cirrhosis, PLC, and acute, subacute liver atrophy formalin fixation and routine paraffin processing sections of liver tissues. HBs-Ag were detected in liver diseases as follows: 110 (52.9%) of 208 cases of atrophic liver cirrhosis, none of 10 cases of micronodular cirrhosis, none of 29 cases of specific types of liver cirrhosis such as biliary, cardiac, parasitic cirrhosis and Wilson\u27s disease, 82 (63.6%) of 129 cases of hepatocellular carcinoma, two (9.5%) of 21 cases of acute liver atrophy, four (22.2%) of 18 cases of subacute liver atrophy, three (15.8%) of 19 cases of chronic hepatitis, active type, and one (14.3%) of seven cases of chronic hepatitis, inactive type. The incidence of HBs-Ag in atrophic liver cirrhosis without hepatocellular carcinoma showed a decrease over fifth decade and also decreased over seventh decade in strophic liver cirrhosis with hepatocellular carcinoma. HBs-Ag was found over two times more in frequency in atrophic liver cirrhosis accompanied with hepatocellular carcinoma (74 of 104 cases; 71.2%) than those without hepatocellular carcinoma. HBs-Ag was demonstrated in eight (32%) of 25 cases of hepatocellular carcinoma without atrophic liver cirrhosis and not in any cases of cholangiocellular carcinoma without atrophic liver cirrhosis and combined type of PLC without atrophic liver cirrhosis. There was no difference in the presence of HBs-Ag between atrophic liver cirrhosis showing active pattern of stromal inflammatory reaction and those with inactive pattern, regardless of having PLC or not. Liver cell dysplasia was found more frequently in atrophic liver cirrhosis with hepatocellular carcinoma (39 of 104 case; 37.5%) than those without hepatocellular carcinoma (13 of 100 cases; 13%). There was significant relationship between the presence of HBs-Ag and the appearance of dysplasia in atrophic liver cirrhosis with hepatocellular carcinoma (32 of 39 cases; 82.1%) and without hepatocellular carcinoma (11 of 13 cases; 84.6%). HBs-Ag was stained in nodular hyperplasia in several cases of atrophic liver cirrhosis. HBs-Ag was demonstrated as "inclusion body type" in tumor cells in two cases of well-differentiated hepatocellular carcinoma. These results showed that atrophic liver cirrhosis and hepatocellular carcinoma, which predominate in Nagasaki area, were associated with the presence of HBs-Ag histopathologically and that HBs-Ag may play a etiological role in most cases of strophic liver cirrhosis and hepatocellular carcinoma