We have constructed a recombinant Oka varicella vaccine virus expressing hepatitis B virus (HBV) surface antigen (HBsAg). HBsAg was synthesized as 26K and 30K proteins in infected cells and secreted into the culture supernatant as 30K and 35K proteins. Inhibitors and glycosidase treatments, and pulse-chase labelling experiments, revealed the glycosylation process of HBsAg. The latter was synthesized as a nonglycosylated 26K protein and subjected to N-linked glycosylation to form a 30K protein with high mannose glycans. Three species of dimers composed of 26K and 30K subunits were then formed with disulphide bonds.Both subunits of the dimers were further subjected to O-linked glycosylation and conversion from high mannose glycans to complex glycans followed by sialylation. Three species of dimers composed of 30K and 35K subunits were secreted into the culture supernatant as HBsAg particles. HBsAg was synthesized, glycosylated with both N-and O-linked glycans, sialylated, and then secreted into the culture supernatant within 1 h. These modifications of HBsAg by glycans might stabilize its structure and enhance its immunogenicity as a live HBV vaccine.

A total of 18 patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) with a 4'-epi-doxorubicin (EDX)-lipiodol emulsion. Infusion of the EDX-lipiodol emulsion (EDX-L) via the hepatic artery was followed by the injection of gelatin sponge in 12 cases. The response and survival of these 12 patients following EDX-L treatment were compared with those of 42 subjects treated with a doxorubicin-lipiodol emulsion (DX-L) and those of 23 patients treated by TAE with gelatin sponge (GS) only. In the group treated with EDX-L, nine cases were AFP-positive in sera and four showed a decrease in serum AFP values to less than 10% of the pretreatment level. Seven cases showed a partial response, and nine cases showed no change in the size of the tumor. In the group treated with EDX-L, nine cases are alive, and the oldest has survived for more than 431 days since the treatment. The half-year survival value was 57%, and the 1-year survival value was 49%. These values did not differ significantly from those calculated for the group treated with DX-L. The 1-year survival value determined for patients treated with a lipiodol emulsion (EDX-L or DX-L) followed by GS was 65%, and the 2-year survival value was 39%. These results rates are significantly better than those obtained in patients treated with GS only (1-year survival, 39%; 2-year survival, 13%.

In order to investigate how chronic liver diseases, including liver cirrhosis and chronic hepatitis, are associate with hepatocarcinogenesis in terms of gene alteration, the methylation states of the c-myc and c-Ki-ras genes were examined in 34 liver tissues from patients with chronic liver disease without hepatocellular carcinoma (HCC), 34 non-tumor liver tissues from patients with HCC, 18 HCC tissues and 31 control liver tissues. The methylation states were analyzed by the Southern hybridization method using the restriction endonuclease isoschizomers MspI and HpaII. The CCGG sites at the second exon of the c-myc gene tended to be more extensively hypomethylated both in chronic liver disease and in non-tumor tissues than in control livers. Whereas the CCGG sites of the c-Ki-ras, and the third exon of the c-myc gene tended to be hypomethylated only in HCC tissues in comparison with other tissue groups. These results suggest that chronic liver disease may be situated between normal liver and HCC based on the state of DNA methylation and associated with the development of HCC through hypomethylation of the c-myc and/or c-Ki-ras gene.

We present a case of portal-systemic encephalopathy due to intrahepatic multiple portal-hepatic venous shunts. A 71-year-old woman was admitted to our hospital because of recurrent episodes of disturbed consciousness. She showed no clinical signs of portal hypertension. Liver function was normal, except for an indocyanine green retention rate of 34% at 15 min and blood ammonia level of 282 microg/dL. Portal venography revealed dilatation of the portal vein and multiple portal-hepatic venous shunts, and a liver biopsy specimen revealed almost normal liver. Further clinical examination revealed a huge pelvic tumour. At laparotomy, two dilated veins were seen to arise from the pelvic tumour with blood flow into the mesentery. The tumour was resected successfully and a histological diagnosis of leiomyoma was made. The blood ammonia concentration decreased to the normal range postoperatively. A follow-up portal venogram demonstrated decreased portal vein dilatation and minor portal-hepatic venous shunts, considered to be congenital in origin. It is concluded that hepatic encephalopathy was produced in this patient due to an excess portal blood flow from the huge pelvic leiomyoma via the mesentery, with portosystemic shunting through pre-existent (probably congenital) intrahepatic anastomoses.

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