We analyzed the characteristics of the 25 patients of non-A, non-B hepatitis according to their responsiveness to interferon treatment using multivariate analysis. Patients were initially analyzed by univariate analysis (t-test, chi-square test) as to 15 variables. From the results of the univariate analysis, we applied 5 variables; age, pretreatment serum of 2-5AS activity, peak 2-5AS after initiation of interferon treatment, increment ratio of 2-5AS and pretreatment serum level of GPT for discriminant analysis. We performed discriminant analysis and computed the discriminant function to discriminate the patients. 18 out of 19 patients (94.7%) were discriminated properly. Discriminant analysis were considered useful to assess the interferon treatment. Next to Age, 2-5AS increment ratio contributed to the discrimination. So patients' reactivity to extermally administered interferon was considered important.

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In situ localization of prolyl 4-hydroxylase, type III and IV procollagen mRNAs were examined to clarify the collagen production in fibrotic human liver. These mRNAs were localized in hepatocytes and mesenchymal cells in the areas of liver fibrosis. In alcoholic liver disease, the expression was promoted, and positive cells were diffusely observed in lobules and nodules. These results suggest that hepatocytes along with mesenchymal cells produce collagens, and correlate with pericellular fibrosis and sinusoidal capillarization in alcoholic liver disease.

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We reported that spontaneous hepatitis (hepatic injury) occurred in LEC rats at around 4 months after birth. In this study, sensitivities of 8-week-old LEC rats to the four hepatotoxins (Dgalactosamine, diethylnitrosamine, carbon tetrachloride and allyl alcohol) were investigated biochemically and histopathologically in comparison with age-matched LEA rats. LEC rats showed a higher sensitivity to D-galactosamine than LEA rats, and the hepatic injury appeared to delay in LEC rats than in LEA rats. Since serum endotoxin levels in LEC rats were higher than those of LEA rats after D-galactosamine treatment, endotoxin may participate in the high sensitivity of the LEC rat liver to D-galactosamine. Serum GPT was slightly higher in LEC rats than LEA rats after injection of diethylnitrosamine, but there were no histopathological differences in livers of the two strains. Liver damages of the LEC rats by carbon tetrachrolide and allyl alcohol were less remarkable than LEA rats, which is probably due to the reductions of drug metabolizing enzyme activity in the LEC rat liver.

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A study was made on the various effects of neonatal thymectomy (NTx) on hepatic injury induced by intravenous infusion of lipopolysaccharide (LPS) one week after administration of heat-killed Propionibacterium acnes in A/J mice. Spleen cells of non-thymectomized or NTx donor mice with hepatitis were transferred to normal or NTx recipient mice to determine whether passive transfer of hepatitis would be possible.
No difference could be observed in the mortality rate within 24 hours after LPS injection, serum GPT level and histological changes in the liver during the acute stage between the two groups. However, in the chronic stage, mononuclear cell infiltration in the portal area was more severe in NTx mice than in normal mice and the levels of autoantibody to liver-specific membrane lipoprotein (LSP) and serum GPT were higher in the former than the latter. Passive transfer of hepatitis was possible only when spleen cells of NTx donor mice with hepatitis were transferred to NTx recipient mice.
These results suggest that spleen cells are more weakly sensitized to LSP in non-thymectomized donor mice with hepatitis and that passive transfer of hepatitis by sensitized spleen cells is suppressed in normal recipient mice. More severe hepatitis in the chronic stage in NTx mice is considered to be attributable to defective suppressor function induced by NTx.

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In mice, peritoneal injection of tumor necrosis factor-α (TNF-α) alone did not cause the liver injury, but simultaneous injection of TNF-α and D-galactosamine (GalN) induced severe hemorrhagic liver cell necrosis which was protected by nifedipine, verapamil, dantrolene, calmidazolium and indomethacin. In cultured rat hepatocytes, neither TNF-α alone nor simultaneous addition of TNF-α and GalN induced liver cell injury. But the serum of a rat intravenously administered with TNF-α caused the cell injury which was protected by nifedipine, verapamil, TMB-8, calmidazolium, indomethacin and aprotinin.
These results suggest that TNF-α is not the factor which can cause liver cell injury by itself, but it may induce some new factors related to liver cell injury involving intracellular Ca²⁺, protease, prostaglandin and complement.

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It has been suggested that autonomic nervous system contributes to the process of the liver regeneration. The lateral hypothalamic area (LHA) is one of important higher centers and controls the function of visceral organs. In this study, changes in the level of monoamines and their metabolites in the LHA were studied after partial hepatectomy in rats by means of a microdialysis technique. Experiments were performed in three groups of rats; 1) 70% hepatectomized rats, 2) 70% hepatectomized rats with vagotomy, 3) sham operation rats. NE, DOPAC and HVA did not change in each group. 5-HIAA, which is the metabolite of Serotonin, increased significantly after 70% hepatectomy without vagotomy. These results suggest that serotonin release in the LHA was enhanced after partial hepatectomy and afferent signals by way of the vagal hepatic branch play an important role in regulation of the liver function and the early process of the liver regeneration.

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Cholecystokinin-8 like immunoreactivity (CCK-8 IR) was measured in brains of Eck fistula and DMN (dimetylnitrosamine)-induced acute hepatic failure dogs which were prepared as experimental models of hepatic encephalopathy, and studies were conducted to investigate correlations among brain CCK-8 IR, ammonia and aromatic amino acid levels in blood and cerebrospinal fluid.
Significant reductions of CCK-8 IR levels were observed not only in all areas of cerebral cortex, thalamus and midbrain of Eck fistula dogs, but also in parietal lobe, temporal lobe and thalamus of DMN-induced acute hepatic failure dogs.
There was a tendency of correlation between reduced brain CCK-8 IR levels and increased ammonia levels in blood and cerebrospinal fluid, but not a tendency of correlation between reduced brain CCK-8 IR levels and increased aromatic amino acid levels in blood and cerebrospinal fluid.
These results suggest that reduced CCK-8 IR levels in brains of dogs with hepatic encephalopathy are concerned with increased ammonia levels in blood and cerebrospinal fluid.

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Effects of diazepam on the binding of γ-aminobutyric acid (GABA) in membranes obtained from brains of acute ischemic hepatic failure rats (AHFR) were studied.
In membranes prepared from brains of control rats, GABA binding was maximally enhanced by 14% at 10^-12M diazepam, while not enhanced at 10^-15-10^-13M diazepam. At concentrations of diazepam higher than 10^-12M, enhancement of GABA binding was reduced. In membranes prepared from brains of AHFR, GABA binding was not affected at 10^-15-10^-13M diazepam, but was enhanced by 7% at 10^-12 M, 32% at 10^-11M, and maximally enhanced by 34% at 10^-10-10^-8M. Scatchard plot analysis revealed that the effect was due to an increase in the affinity of the low affinity site in membranes prepared from brains of control rats. In membranes prepared from brains of AHFR, the effect was due to an increase in both the affinity and the density of the low affinity site. The stimulation of GABA binding by diazepam in membranes prepared from brains of both control rats and AHFR was significantly inhibited by Ro 15-1788, a selective competitive antagonist of diazepam. The degree of the enhancement in GABA binding by diazepam was significantly higher in AHFR when compared with control rats. These results suggest that the alterations of GABA-benzodiazepine receptor complex exist in AHFR and may possibly be associated with hepatic encephalopathy.

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Monoclonal antibody clone-8, derived from splenocytes of a Balb/c mouse immunized with a human hepatoma cell line HuH-7, belonged to an IgG1 which recognized membranous component expressed on hepatomas. Biochemical characterization of the antigen revealed that it was a 40, 000 dalton glycoprotein. Concerning the expression of this antigen, tissue sections of hepato-cellular carcinoma (HCC), liver cirrhosis (LC), chronic hepatitis (CH), normal organs and human HCC cell lines (HLE, HLF) were tested by means of an immunoperoxidase assay. Seven of 15 HCC, HLF, and two tissues from benign liver diseases were reacted with clone-8. Flow cytometry analysis revealed that the expression of antigen detected by clone-8 increased with progress of the cell cycle from G0 to G2/M. Therefore, it seems that the antigen is related to the phenomena taking place in cell proliferation.

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A case of granulomatous hepatitis caused by BCG immunotherapy for carcinomatous metastasis of unknown origin to cervical lymph node in a 62-year-old female is reported. After BCG injections of 3 times of every 3 months, general malaise, anorexia, fever and jaundice developed gradually. On admission, enlarged right cervical and left axillay lymph nodes were palpable and skin ulcer at the BCG injected region in the left shoulder were seen. Liver function tests revealed, T. Bil. 71mg/dl, GOT 123U, GPT 147U, ALP 16.3U, γGPT 46μU/ml. Biopsy specimen of the enlarged cervical lymph node showed undifferentiated carcinoma of unknown origin. Histology of the skin ulcer showed scattered non-caseating epithelioid granuloma with giant cells in the subcutaneous tissue. Liver biopsy specimen also showed similar epithelioid granulomas in the portal tracts and parenchyma. Although, Myobacterium bovis BCG could be detected in neither liver tissue nor skin ulcer by the routine ZiehlNeelsen stain, diagnosis of granulomatous hepatitis caused by BCG injection was made.

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