We measured (2'-5') oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum in chronic hepatitis B (CHB) with acute exacerbation. Elevated levels of 2-5 AS activity in PBMC and serum in CHB with acute exacerbation were found, while in CHB without acute exacerbation the levels were similar to healthy subjects. Increase in 2-5 AS activity was associated with increase in serum aminotransferases rather than that in HBV-associated markers such as DNA polymerase and serum HBV DNA. These suggest that in vivo IFN system may be activated during acute exacerbation in CHB, and that this activation may not be a result of HBV multiplication alone, but also of a host-immune response to HBV multiplication. Three patients among 7 CHB with acute exacerbation were treated with IFN. Before treatment, all of them had elevated 2-5 AS. None of them cleared HBeAg after treatment. This suggests that IFN treatment was not effective during acute exacerbation since in vivo IFN system has already been activated. Measurement of 2-5 AS in CHB may be useful to determine the optimal timing of IFN treatment.

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The development of autoimmune hepatitis produced by immunizing Wistar rats with syngeneic liver proteins appears to be strain-specific since Lewis rats were relatively resistant, whereas Wistar rats are fully susceptible. Mononuclear cells infiltrating into liver (MIL) were indentified by immunohistochemical techniques with monoclonal antibodies (MoAb) specific for subpopulations of rat lymphocytes. In the portal areas there is a marked enrichment for RLyt-2 positive cytotoxic T lymphocytes (CTL). Subpopulations of MIL, spleen cells and peripheral blood lymphocytes (PBL) were indentified by immunofluorescence flow cytometry. We found the relatively small number of RLyt-1 positive cells as compared to the sum of RLyt-2 positive cells and W3/25 positive cells in MIL and PBL. Reactivity of various MoAb revealed that a population of RLyt-2 positive, but RLyt-1 negative or dull positive T lymphocytese is present in the liver. These findings support the notion that liver cell injury in experimental autoimmune hepatitis may, at least in part, be mediated by CTL.

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When heat-killed Propionibacterium acnes, a gram-positive anaerobe, is intravenously injected into mice followed by an intravenous injection of gram-negative lipopolysaccharide (LPS) 7 days later, most of the mice die of massive hepatic cell necrosis within 24 hours of LPS injection. Using this acute hepatic failure model, tryptophan metabolism in the liver, brain and kidney was studied. As a result, the tryptophan level remarkably increased in all three organs, and the metabolism of both the tryptamine pathway and serotonin pathway was induced. However, in the brain, the increase in tryptamine metabolism was higher compared to that of serotonin. This suggested that the metabolites of tryptamine may be involved encephalopathy.

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The purpose of this study was to evaluate lipid metabolism and development of fatty liver after simultaneous major resection of the liver and pancreas in dogs, with special reference to pancreatic endocrine function.
Insulin secretion decreased after more than 92% pancreatectomy alone, accompanied by development of diabetes mellitus, hyperlipemia, and fatty liver in all dogs. However when 70% hepatectomy was performed simultaneously with more than 92% pancreatectomy, insulin secretion decreased to a lesser extent and insulin uptake by the liver markedly decreased, diabetes mellitus subsequently developing in only 3 (37.5%) out of 8 dogs. In 5 of 8 dogs which underwent more than 92% pancreatectomy simultaneously with 70% hepatectomy, neither diabetes mellitus nor hyperlipemia and fatty liver developed, preserving an almost normal insulin level in the peripheral blood, as a result of a minor decrease in insulin secretion and a marked reduction of insulin uptake by the liver.

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The aim of this study is to elucidate the difference in hepatic hemodynamics and oxygen consumption between alcoholic and nonalcoholic obesity-related fatty liver. Although the degree of histological fat was equal between the two groups, an index of the regional liver blood flow and the hepatic oxygen consumption were lower in alcoholic fatty liver than in nonalcoholic fatty liver. The oxygen saturation of hemoglobin in local liver blood was, however, higher in alcoholic fatty liver than in nonalcoholic fatty liver. These results suggest that an increase in oxygen extraction was not observed in alcoholic fatty liver, in spite of a reduction of oxygen supply to the liver.
It is concluded that the impairment of hepatic circulation and oxygen consumption was more serious in alcoholic fatty liver, possibly contributing to a different prognosis of two types of fatty liver.

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To assess the effect of splenectomy on hepatic fibrosis, male Sprague-Dawley rats were injectedpig serum intraperitoneally for 10 to 12 weeks with Or without splenectomy.
The degree of hepatic fibrosis, evaluated with histological findings and hydroxyproline content, was significantly greater in sham-operated animals than in splenectomized animals.
Hepatic prolyl hydroxylase activity in splenectomized group was lower than that of sham-operated group, although not statistically significant, whereas collagenase activity in the latter group was rather higher than that of the former group up to 8 weeks and thereafter the tendency was reversed.
Splenectomy was found to be effective in preventing rat hepatic fibrosis up to 12 weeks, however, the effect was not observed when splenectomy was done at 6th week during a course of 12 weeks pig Serum treatment.
These results suggest that the effect of splenectomy is preventive against pig serum induced rat liver fibrosis, at least, at certain stage. Although, mechanisms involved are remained to be elucidated.

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The histopathological process of experimental liver cirrhosis induced by long term oral administration of furfural was investigated. The cell kinetic study of hepatic cells during this experiment was also carried out using BrdU-anti-BrdU method. From 60th experimental day, potal fibrosis and pericellular fibrosis in the vicinity of periportal areas appeared. In the 90th experimental day, the liver showed macro-scopically whitish granular appearance corresponsing to histological bridging fibrosis. Thereafter porto-portal and porto-central fibrosis extensively progressed followed by formation of apparent pseudolobule in the 150th experimental day. BrdU immunohistochemical lebeling indices of hepatic cells in the experimental groups were caliculated 2-4% which were significantly higher than those in control animals. These observation revealed that the process of this experimental hepatic injury consisted not only of simple fibrosis but of concomittant hepatic parenchymal cell proliferation with a similarility to human liver cirrhosis. It is suggested that furfural induced liver cirrhosis is an usuful experimental model for analysing developmental process of human post hepatitic cirrhosis.

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This study was designed to investigate the effect of cimetidine on carbon tetrachloride (CCl₄)-induced liver injury. A dose of 150mg/kg BW of cimetidine was pretreated 1 hour prior to 1.0ml/kg BW CCl₄ injection. Cimetidine significantly reduced increases in serum GOT and GPT, and ameliorated the histological findings by CCl₄. Cimetidine inhibited increases in MDA in both blood and liver. Contents of hepatic cytochrome P-450 were preserved by cimetidine. These results indicate the important role of lipid peroxidation in the pathogenesis of CCl₄ hepatotoxicity and cimetidine may exert the protective effect by inhibiting the lipid peroxidation at the level of cytochrome P-450.

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The antitumor effect of human interferon-γ (IFN-γ) with/without polyprenoic acid (E5166) on the human hepatoma cell line (HuH-7 cells) were investigated. The cell growth in vitro was almost never inhibited when IFN-γ was given at the concentrations of 1×10³ to 1×10⁴IU/ml, but the cell growth was remarkably inhibited when both IFN-γ and E5166 was given. The growth rate to transplanted tumors in nude mice was investigated, using 4 groups treated with IFN-γ with/without E5166 in different dose for 2 weeks. Administration of IFN-γ in higher dose showed the remarkable antiproliferative effect on human hepatoma cells. It is suggested that the different effect of IFN-γ between in vitro and in vivo may be based upon the different action of IFN-γ. In conclusion, our results indicate that administration of IFN-γ in higher dose may be effective in therapy of HCC, and particularly in concomitant use of E5166.

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Portal vein blood flow (PVF) and splenic vein blood flow (SVF) were measured by the ultrasonic pulse Doppler method on 100 cases of patients with various types of hepatic diseases. From these values obtained above, the blood flow ratio of the splenic vein to the portal vein (S/P ratio) of each patient was calculated. Among the subjects, 22 patients with cirrhosis were subjected to various tests concerning the blood flow dynamics, i.e., hepatic vein pressure gradient (HVPG), cardiac index (CI), and azygos blood flow (ABF). S/P ratios were significantly higher in the cirrhosis group as compared with other hepatic disease groups. In addition, S/P ratios showed significant positive correlation to HVPG and ABF. Among the patients with cirrhosis, significant high S/P ratios were observed in cases with esophageal varix as compared to those without this lesion. As described above, S/P ratios obtained by non-invading ultrasonic tests were supposed to enable the evaluation of shunts, especially of upper shunts intimately related to the existence of esophageal varix.

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We present six patients with severe joint pain who were found to have hepatitis B virus (HBV) infection and the pathogenesis is discussed in this paper.
The sera from five patients in the acute phase of their joint symptoms were obtained, so we determined the circulating immune complexes (IC) which had been thought to be the pathogenesis of arthritis.
IC were detected in 2 out of 5 patients (40%) by using C1q solid phase enzyme immunoassay but were not detected in all patients by Raji cell enzyme immunoassay. Alternatively, HBs antigen·antibody IC by polyethleneglycol-trypsinization method were detected in 4 out 5 patients (80%). The levels of C3 and C4 were depressed in 2 (40%) and 3 patients (60%) respectively.
These results suggest that circulating IC may not be related closely to arthritis occuring in prodrome of acute hepatitis type B.
Therefore, it is also important to investigate the local deposition of IC or HBV replication in joints as one of the extrahepatic menifestations.

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We reported 3 patients of asymptomatic HBsAg carriers who developed fulminant hepatic failure following withdrawal of steroid therapy. Basic disease for steroid therapy was as follows; malignant lymphoma, nephrotic syndrome and arthritis. These cases died without any improvements despite that all reliable treatments were provided. Concerning development of fulminant hepatic failure in this condition, it seems that immunosuppressive therapy permit replication of HB virus resulting in massive hepatic destruction based upon rapidly recovered immune response after its withdrawal.
Therefor, we have to pay attention to steroid therapy for disease complicated in HBsAg carrier.

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A rare case of diffuse midzonal and periportal hepatocellular necrosis developed in a 2-month-old male with congenital heart disease was reported. Coagulative hepatocellular necrosis was seen in all midzonal areas and around 67% of the portal triads and 320% of the central veins of the whole liver. In the present case, the simultaneous appearance of hepatic necrosis and multiple organ failure suggests that endotoxaemia, in addition to severe hypoxaemia induced by congenital heart disease, related to the development of the hepatic necrosis, because a major cause of multiple organ failure is endotoxaemia. In the present case, endotoxaemia was implyed by a decrease in platelets and leukocytosis. The peculiar hepatic necrosis in the present case may be formed by confluence of enlarged focal necrotic areas and survival of the hepatocytes around the portal triads and the central veins fortunately kept blood supply, because it is known that hypoxaemia enhances the endotoxininduced hepatic injury.

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The authors reported two cases of Rendu-Osler-Weber disease in which intrahepatic arterioportal and arteriovenous fistula could be confirmed angiographically.
In the first case, diagnosis of the disease could be established on the basis of not only classical clinical features but also angiographic findings through the celiac artery.
In the second case, imaging diagnostic procedures, especially selective angiography through the celiac artery revealed apparent tortuousness of intrahepatic branches of the hepatic artery as well as arterioportal fistula, while characteristic clinical features were scarecely recognizable. Laparoscopy guided needle biopsy of the liver clarified definite dilatation of intrahepatic blood vessels histologically.
The estimation of oxygen saturation with blood taken off through the inferior vena cava by means of cardiac catheter showed oxygen stepup phenomenon at the confluence of hepatic vein.

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A case of meningioma with multiple liver metastases was reported. A 33-year-old man was diagnosed as meningioma and the tumor was sresected in 1978. On June, 1984, he comlained of right upper abdominal pain. Ultrasonography revealed multiple liver tumors. Metastatic liver tumor was suspected. On October, 1984, extended right lobectomy was performed. Histological finding was very similar to that of the brain tumor resected in 1978. On June, 1985, a recurrence was detected in the remnant liver on CT examination. On August, 1985, partial resection of the liver was performed.
Any other report on therapeutical operation for liver metastasis of meningioma cannot be found.

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