The localization of HBx antigen in the liver biopsy tissues from 36 patients with chronic hepatitis B was investigated by indirect immuno-peroxidase staining with rabbit anti-serum to synthetic HBx peptide (N-terminal amino acid sequence 116-134). At the same time, the localization of HBc antigen in the liver tissues was also investigated by the same method to compare with that of HBx antigen. Twenty-one of 36 patients (58.3%) with chronic hepatitis B were found positive for HBx antigen. HBc antigen was positive in 61.1% of these patients, and this antigen was localized almost at the same sites of the liver tissues as HBx antigen. In addition, the changes of intrahepatic HBx antigen before and after IFN treatment were examined in 18 patients with chronic hepatitis B. While HBx antigen was positive in 11 of these 18 patients before the treatment, 4 patients became negative for HBx antigen, and 2 showed decreased grade of the antigen after the treatment. HBc antigen was also disappeared or decreased in 13 of the patients. These results suggest that the presence of HBx antigen is associated with active viral proliferation in persistent HBV infection.

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We examined C-100 antibody of 1619 cases of NANB chronic liver disease and evaluated relationship among historogical stage, sex, rate and titer of C-100 antibody. Positive rate of C-100 antibody was as follows; in men the rate is 73.8%, in women the rate is 65% and in men the rate is higher. In cases of liver cirrhosis, in men the positive rate of C-100 antibody is 76.2% and in women that is 56%. In 53 cases of 1619 cases of NANB chronic liver disease, we examied the change of C-100 antibody titer more than 10 years. In 14 cases the C-100 antibody became negative in natural course. 11 cases of this 14 cases were female and had liver cirrhosis histologically and 4 cases had normal GPT and became negative HCV-RNA.

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Hepatitis C virus (HCV) is a major causative agent of post-transfusion non-A, non-B hepatitis and sporadic hepatitis throughout the world. The HCV genome has a single strand RNA molecule of the 10 kb length, which shows the high divergence in nucleotide and amino acid sequences. Virologically, HCV is considered to be closely associated with flavivirus and pestivirus. Anti-C-100 antibody assay system using recombinant protein of C-100 region showes high relation to non-A, non-B hepatitis. Because C-100 region was thought to be highly conserved, we developed RT-PCR using mixed primers of C-100 region for direct assay of HCV. Japanese variants of HCV cloned by this method showed divergence to prototype of HCV. The cDNA fragments of 98-nucleotide length showed 65-67% homology at the nucleotide level and 81% homology at the amino acid level compared with the prototype HCV cDNA.

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A study was conducted to investigate effects of branched-chain amino acid (BCAA) enriched-nutrient mixture on albumin metabolism in cirrhotic patients. The nutrient-mixture was given at the dose of 150g/day (17.7g BCAA/day) for 8 weeks to 5 cirrhotic patients with hypoalbuminemia (<3.5g/dl).
Kinetic parameters of albumin metabolism following intravenous injection of ¹³¹I-labelled human serum albumin were analyzed before and at 8 weeks after administration of the mixture, the following results were obtained;
1. Plasma BCAA (valine) level and BCCA/AAA (aromatic amino acid) molar ratio significantly elevated (P<0.01 and 0.05 respectively).
2. The biological half life of albumin was significantly shortened (P<0.01), while the degradation and synthesis rate of albumin significantly increased and recovered toward the control range. (P<0.05 and 0.01 respectively).
3. No significant changes were observed in body weight, plasma volume, plasma albumin concentration, intravascular albumin pool, and total albumin pool.
4. As to the relative distribution of albumin, a significant shift from the extravascular pool to the intravascular one was noted.
In conclusion, administration of BCAA enriched-nutrient mixture to cirrhotic patients seems to be clinically useful by improving albumin metabolism, in paticular albumin synthesis rate, even before serum albumin level increases.

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The structure of intrahepatic microvessels after hepatic arterial embolization with several embolic meterials was investigated by scanning electron microscopy (SEM).
After the intrahepatic arterial injection of Lipiodol, destruction of capillary vessels in peribiliary plexus (PBP) was noted. After the intrahepatic arterial injection of Gelfoam, occlusion of the terminal branches of hepatic artery (about 30μm in diameter) and proliferation of the collateral vessels were noted. The Ivalon (1mm in diamter) had no significant effects on structural changes of the terminal branches of hepatic artery. It appears that the Ivalon embolized the extrahepatic artery and it caused the proliferation of extrahepatic collateral vessels instead of intrahepatic collateral. Destruction of PBP was noted after the intrahepatic arterial injection of Degradable Starch Microspheres (DSM).
The influence of embolic materials on intrahepatic microvessels after the hepatic arterial embolization was clarified by study with SEM.

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It has been widely known that decreased portal vascular beds and increased hepatic arterial beds are common findings in human cirrhosis, whilst the reason of the latter is still enigma. To clarify what the hepatic artery's role is at pseudolobules, the investigation of scanning electron microscopy was performed using the microvascular casts of the experimental rat cirrhosis. Male Wistar rats were injected subcutaneously carbon tetrachloride twice each week for 12 weeks, in addition 0.06% 3'-methyl-4-diethylaminoazobenzen was administered following 10 weeks. According to the formation of micronodular cirrhosis, conspicuous vascular change in portal vein branches was appeared such as dear horn like structure and coral like network. Pseudolobules were mainly fed by the portal blood, on the contrary, the hepatic artery assumed a minor role for the intrapseudolobular circulation. During the course of 3'-Me-DAB, the macronodular cirrhosis was developed, however, the hepatic arterial alteration was as same as in the micronodular cirrhosis. The intrapseudolobular circulation was similar to the micronodular cirrhosis. It was concluded that pseudolobules in the experimental rat cirrhosis was mainly fed by the portal vein and the hepatic artery had a minor role in the circulation. The increase of the hepatic arterial beds might be more closely related to stromal inflammatory reaction.

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Postmortum specimens of the liver from 20 patients who had undergone allogeneic bone marrow transplantation (BMT) for leukemia (17), malignant lymphoma (2) and aplastic anemia (1) were examined. Histologically, veno-occlusive disease (VOD), obliteration or stenosis of small hepatic venules, were observed in 8 patients (40%). Five patients had a subclinical course. Three cases showed progressive VOD who died of hepatic insufficiency. Two of these 3 patients developed progressive jaundice and ascites occurring in 160th and 210th day after BMT, respectively. We should be aware of late on set of VOD after BMT.

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A case of fulminant hepatitis due to a herbal drug was reported. A 62-year-old male was admitted to Iwate Medical University Hospital because of jaundice and malaise after taking a herbal drug (Kinshigan) containing 17 herbal medicines for five weeks. He had a previous history of jaundice following Kinshigan intake. On admission, prothrombin time was prolonged (28%) and CT scan revealed markedly atrophic liver. Viral markers were negative for hepatitis A, B and C. Despite of intensive therapies including plasmapheresis, he died from hepatic coma with multiple organ failure after 4 weeks. The liver weighed 495g, showing the histological features of massive hepatic necrosis. Nine cases of Kinshigan-induced hepatic injury have been reported to date. It was noteworthy, presumably due to the preconception that herbal medicine is safer than western drugs, that the patients tended to have multiple episodes of hepatitis following repeated intake of the drug.

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Portal hypertension results in not only esophageal varices but also many other collateral shunts. We report a case of Inose type hepatic encephalopathy apparently caused by a superior mesenteric vein-inferior vena cave shunt. Preoperative angiography through the superior mesenteric artery failed to demonstrate the portal vein, revealing instead a collateral SMV-IVC shunt. Preoperative Doppler ultrasonography showed reverse circulation in the portal vein. Normal circulation was restared by surgical closure of the shunt; symptoms and liver function also improved. Portography 8 months later clearly identified the intrahepatic portal vein, with no evidence of recurrent collateral circulation. The above case demonstrates the efficacy of surgical closure in the treatment of porto-systemic shunt.

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We report an autopsy case of neoplatic angioendotheliosis (NAE) with extravascular tumor formation in the liver. A 77-year-old woman, who had been followed with chronic hepatitis of ten years' duration was admitted to our hospital for a treatment of ascites and unknown fever. She was pointed out liver cirrhosis by ultrasonogram and biochemical examination on admition. Ascites and unknown fever did not improve by diuretics and antibiotics. Hypoechoic tumor, approximately 2cm in diameter, was detected in S₅ area of the liver by ultrasonogram, and hepatocellular carcinoma was most suspected. She died of hepatic and renal failures one month after admission, and autopsy was performed.
Grossly, whitish solid mass with well-demarcated margins, measuring 2.0×1.7cm in size was located in S5 area of the liver. Histologically, the tumor consisted of a solid proliferation of large blastoid cells with a little fibrillay elements. Numerous tumor cells were also found in the lumen of the small vessels in various organs including the liver. The tumor cells were found to be positive for both leukocyte common antigen and pan B cell antigen. The liver tumor was diagnosed as extravascular tumor formatian of NAE.

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The therapeutic effect of intracystic lavage with ethanol on cystadenocarcinoma of the liver in a 73-year-old female is reported. She complained of abdominal fullness, and US and X-ray CT examinations revealed that a large cystic tumor with a papillary solid portion occupied almost the entire right lobe of the liver. Cytology of the cystic fluid was class V, adenocarcinoma. Surgical resection of the tumor was excluded due to the complication of congestive heart failure, and intracystic lavage with ethanol, that has been reported to be effective on benign cystic lesions, was employed. After four cycles of injections, each of which used approximately 50ml ethanol, her subjective symptoms disappeared. The volumes of both the whole cystic tumor and the intracystic papillary solid portion were estimated by CT, and were found to have decreased. Autopsy confirmed this effect revealing almost total necrosis of the intracystic layer and papillary solid portion. Intracystic lavage with ethanol appears to be an alternative treatment for hepatic cystadenocarcinoma in patients who have a contraindication to surgical resection.

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