The relationship between the ALT value of blood donors and incidence of post-transfusion hepatitis was investigated. One hundred eighty-seven recipients received only single component of blood of which the ALT value of donor was investigated without any exception. The recipients received 1148 units of blood within 7 days for the first time. Twenty-five recipients (13.4%) received at least one unit of high ALT blood (donor ALT>26 KU). These recipients shared 9% of non-hepatitis patients, 19% of hepatitis patients. The share in hepatitis patients of high ALT recipients was significantly higher than the share in non-hepatitis patients. The incidence of post-transfusion hepatitis may decrease using the bloods whose donor ALT were below 25 KU only.

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We investigated the relationship between pre-S Ag titers and the prognosis of 25 chronic hepatitis B patients with IFN therapy. Before IFN therapy, pre-S1 Ag and pre-S2 Ag titers of responders were 6.23 ±1.09 and 4.46 ±1.27. Those of nonresponders were 8.00 ±2.17 and 5.83 ±1.40, respectively. Both titers of the responders were significantly lower than those of the nonresponders. Furthermore, pre-S Ag titers had remained high or become high 3 months before HBeAg turned positive again. These observations suggest that the titers of pre-S1 Ag and pre-S2 Ag may be useful to predict the prognosis of patients with IFN therapy.

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Sixty-eight surgical cases of hepatocellular carcinoma (HCC) were examined by light and electron microscopy for macrophages in the cancerous tissues. Macrophages were demonstrated in the blood spaces of cancerous tissues in 63 (92.6%) of 68 HCCs by light microscopy and in 16 (88.9%) of 18 HCCs by electron microscopy. Macrophages were most frequent in well-differentiated HCCs with a thintrabecular pattern. Well-differentiated HCC seemed to contain more macrophages than poorlydifferentiated one. In most cases, the number of macrophages in the cancerous tissue was fewer than that of Kupffer cells in the surrounding liver tissue. On the other hand, hyperplastic nodules and focal nodular hyperplasias contained macrophages as well, and the number of macrophages in these nodules was greater than or similar to the Kupffer cells in the surrounding liver tissue. The pattern of localization in the blood spaces, morphological features including the presence of abundant lysozyme and D-PAS activity suggested that the macrophages in the cancerous tissue might be the same as the Kupffer cells.

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The antitumor effect of human interferon-γ (IFN-γ) with or without polyprenoic acid (E5166) on human hepatoma cells (HuH-7) transplanted into nude mice was investigated. Nude mice xenografted tumors were divided into 8 groups and treated for 2 weeks in accordance with different dose of IFN-γ (2×10³IU, 1×10⁴IU, 5×10⁴IU, 1×10⁵IU) with or without E5166 (40mg/kg). In the groups treated with IFN-γ alone, a dose of 1×10⁵IU/day showed the most remarkable antiproliferative effect to transplanted HuH-7 cells. However, this effective with IFN-γ was not always dose dependent. On the other hand, in the groups treated with combination of IFN-γ and E5166, additional antitumor effect of E5166 to IFN-γ was not observed, although a combination of IFN-γ in dose of 5×10⁴IU/day and E5166 showed the same effect as IFN-γ in a dose of 1×10⁵IU/day. In conclusion, it is suggested that administration of IFN-γ in higher dose is useful in therapy of hepatocellular carcinoma and combination with IFN-γ and E5166 can reduce the dose of IFN-γ.

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Impacts of medroxyprogesterone acetate (MPA) on hepatocarcinogenesis was investigated and the levels of sexual hormone receptors were measured in rats.
The diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzen (3'-Me-DAB) was given to A, B, C, and D group for 75 days and to E, F, G, and H group for 170 days. In the former MPA was administered 0, 60, 120, and 180mg/kg/day for 100 or 150 days, respectively. In the latter it was administered 0, 30, 60, and 120mg/kg/day for 180 days, respectively. MPA was given with a gastric tube three days a week.
Inhibition of carcinogenesis (p<0.01) and the tumor growth (p<0.05), decrease in the mitotic index (p<0.05), and prolongation of the survival period (p<0.05) were observed in the MPA groups.
It was suggested that MPA inhibited hepatocarcinogenesis with 3'-Me-DAB and its effect might relate to increase in ER of the tumor-free tissue and be mediated with the tumor PR.

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This study was undertaken to investigate the effect of a new extracorporeal system combining direct hemoperfusion (DHP) and veno-venous bypass on the elimination of anticancer drugs during intraarterial chemotherapy of the liver. Adriamycin (ADR, 3mg/kg) and Mitomycin C (MMC, 1mg/kg) were given to mongrel dogs through hepatic artery in three different duration of 1, 10 and 20 minutes. Blood flow through DHP averaged 200ml/min. In dogs without DHP (group I, n=4), plasma levels (μg/ml) of ADR and MMC in right external jugular vein (peripheral level) rapidly increased with one minute infusion, reaching the peak values of 6.61±2.44 (mean±SD) and 2.20±1.05 respectively. With DHP under single venous bypass for the blood access from IVC (group II, n=5), the peak values were lower reaching only 1.25±1.02 and 0.79±0.52. In addition, the peak levels were markedly reduced by DHP under hepatic venous isalation using veno-venous bypass (group III, n=8), the values being 0.41±0.15, and 0.13±0.07. These were 6.2 and 5.9% respectively versus each corresponding value of graup I (p<0.01). The longer the duration of infusion, the higher the removal rates tended to be in group III. In conclusion, extraregional distribution of anticancer drugs can be minimized by this extracorporeal system and therefore dose escalation may safely be performed during intraarterial chemotherapy of the liver.

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Seventy-two patients with hepatic malignancies (hepatocellular carcinoma 13, cholangoicellular carcinoma 6, metastatic gastric carcinoma 27, metastatic colorectal carcinoma 18, others 8) were treated with intermittent intraarterial infusion chemotherapy using a subcutaneously implanted silicon reservoir and campared with 268 patients receiving other conventional chemotherapies (bolus one shot chemotherapy into hepatic artery, intravenous chemotherapy, oral chemotherapy, etc). Fiftyfour patients were catheterized from a branch of left subclavian artery and 18 patients were cathterized via the gastroduodenal artery. All patients received a intraarterial infusion chemotherapy employing either MFC or FAM at intervals of two weeks.
Among 53 patients, where clinical evaluation of initial response of chemotherapy was possible, partial response (PR) were obtained 23 cases, 43% (hepatocellular carcinoma 5/10, 50%, gastric carcinoma 8/17, 47%, colorectal carcinoma 7/14, 50%, etc).
Survival probability at 6 months and 12 months calculated by Kaplan-Meier method were 40% and 10% for hepatocellular carcinoma, 70% and 40% for gastric carcinoma, and 89% and 59% for colorectal carcinoma respectively. These data demonstrated the significantly higher survival rate compared with other chemotherapeutic method by means of generalized Wilcoxon test (p<0.01-0.05).
No severe complication was observed in this method without two cases with brain infarction and gastrointestinal bleeding.
We concluded that this method was well tolerated procedure in patients with advanced hepatocellular carcinoma and metastatic liver carcinoma.

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To investigate the ubiquitination of intermediate filaments (IFs) of hepatocyte in Mallory body (MB) formation, we performed immunofluorescence and immunocytochemistry for cytokeratin IFs and MBs of mouse liver fed griseofulvin for 1 to 6 months. Immunofluorescence using cytokeratin monoclonal antibody (RPN 1160) for control mouse was seen at the cell border, in the cytoplasm and around the nuclear rim of the hepatocytes, however, monoclonal antibody (IgM) specific to ubiquitin weakly stained these areas. MBs in griseofulvin-fed liver cells were stained in a similar pattern by an ubiquitin monoclonal antibody and a monoclonal antibody specific for cytokeratin. Immunocytochemistry revealed that the ubiquitin antiserum heavily decorated the IFs around MBs as well as MB filaments. The IFs of hepatocytes in controls were weakly decorated by the ubiquitin monoclonal antibody. Although the role of ubiquitin in the degradation of IFs is elucidated partially, our results indicate that excessive ubiquitination of IFs is noted in MB formation.

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Tritiated platelet activating factor (³H-PAF) was injected into the tail vein of rats and the radioactivities in blood, lung, spleen, liver and brain were determined at valious time intervals by a liquid scintillation counter. The radioactivity in 0.1g of various tissues reached at their maximus 5min after ³H-PAF injection and declined thereafter. These declines were especially remarkable in blood, spleen and lung, while the radioactivity was remained for considerably longer time in liver and kidney. When total radioactivity incorporated into and remained in various organs were calculated, it was shown that the liver was the most injection of ³H-PAF. On the other hand, incorporation into the brain was very low and no change in radioactivity was detected during the observation. These results suggested that the liver might be an important organ in metabolism of PAF and PAF might play some role in inflammatory reaction in liver.

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The concentration of mRNAs of rat aldolase A, B, C, α-fetoprotein, and albumin were examined during EGF-stimulated primary hepatocyte culture in rats.
The concentration of aldolase A (oncofetal type) and a-fetoprotein mRNA increased. S1 analysis revealed that among two types (M type and AH type) aldolase A mRNA, only AH type (adult rat liver type) was expressed. In contrast, aldolase B (liver type) and albumin dramatically decreased in concentration.
These findings indicate that the growth activated and dedifferenciated hepatocyte may produce the aldolase A and C mRNA, however, resting hepatocyte may continue to function as a differentiated cell and produce the aldolase B mRNA.

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In order to clarify the cytoprotective role of superoxide dismutase (EC 1.15.1.1 SOD), the localization of Cu, Zn SOD in rat liver tissue following carbon tetrachloride intoxication was investigated, using anti-rat Cu, Zn SOD monoclonal antibody. The antibody was prepared using purified rat Cu, Zn SOD as the antigen. In control liver, Cu, Zn SOD was difusely stained in the lobules. Three different localization patterns of Cu, Zn SOD in hepatocytes could be recognized; cytoplasmic, nuclear, and both cytoplasmic and nuclear localization. Immunoelectron microscopic observation revealed the localization of Cu, Zn SOD in the cytosol matrix, membrane of the rough endoplasmic reticulum and nucleus. Following administration of CCl₄, Cu, Zn SOD was strongly localized in ballooning degenerative hepatocytes and present in the cytoplasm of fatty degenerative hepatocytes. Immunoelectron microscopic observation revealed the reaction products localized in the cytosol matrix and on the membrane of rough endoplasmic reticulum around fat droplets. These findings suggest a close relation of superoxide radical to the etiology of liver damage following carbon tetrachloride intoxication.

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A 52-year-old male was adrnitted for evaluatian of liver dysfunctian. Labaratary examinatian revealed elevation of serum levels of ALP, γ-GPT and LAP. But level of total bilirubin was within normal limit. Serum levels of IgG and IgM elevated and antimitochondrial antibody was positive. Liver biopsy showed chronic nonsuppurative destructive cholangitis, which was pathognamic as stage 1 of primary biliary cirrhosis (PBC). Because of no symptoms such as jaundice and itching, he had been managed at the outpatient clinic. After three and half years from the first admission, a cholecystectomy was performed for cholecystitis. Macroscopic finding of the liver during operation showed large nodular liver. Simultaneous needle biapsy of the liver showed portal-portal bridging formation by collagen fiber and pseudolobule formation. Because of the scarring of portal area was developing, the interlobular bile duct was obscure. These findings were compatible with stage 3 or 4 of PBC (Sheuer). It was suggested that this case was note-worthy for discussing prognosis of PBC and its histalagical course of the liver.

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Three cases of asymptomatic primary biliary cirrhosis (a-PBC), for whom ursodeoxycholic acid (UDCA) was very effective, were studied clinico-pathologically. UDCA was given at a dose of 600mg per day in each patient, and given for 12 months in case 1, 6 months in case 2 and 5 months in case 3. Histologically, case 1 was in stage III, case 2 in stage III, and case 3 in stage I. In the biochemical data, all of three patients demonstrated the improvement in their serum levels of ALP, _γGPT and IgM. The titer of AMA fell obviously in one of them (case 1). In the histological study, it was demonstrated that infiltration of inflammatory cells in the portal tract and the portal enlargement were significantly improved, and that chronic non-suppurative destructive cholangitis was improved in common with all of three patients. In one of them (case 1), it was demonstrated that piecemeal necrosis was markedly improved. These findings suggest that not only biochemical data but also histological basic lesion of PBC may be improved due to UDCA administration. Consequently, it is suggested that UDCA may be very effective treatment for a-PBC.

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Arterial Embolization is said to be contraindicated in cases of Hepatocellular Carcinoma (HCC) in which the tumor has invased into the portal trunk (Vp₄ TT). We report a long surviving HCC case with Vp₄ TT treated by embolization. A 62-year old male patient suffered from HCC with Vp₄ TT and cavernous transformation in the liver hilum. Right lobe in which the main tumor was located shrunk and left lobe was enlarged compensatolly. He is being treated by repeated Embolization (Twice) and still surviving and well 5 years 3 months from initial Embolization. Factors which may contributed to long surviving HCC with Vp₄ TT treated by Embolization are discussed.

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The patient was 71 year old man, and had suffered from chronic hepatitis.
On echogram, hyperechoic space occuping lesions were observed in subsegment 5 (S₅) and subsegment 3(S₃). Alpha-fetoprotein (AFP) was elevated in serum. On hepatic angiogram, tumor stain accompanied with arterio-portal shunt was revealed in S₅, but no tumor stain in S₃. On pathologic examination, the former showed nodular type with an extacapsular invasion and Edmondson's type (Ed) III with strong AFP stain, but nodular type without any invasion and Ed II with scarece AFP stain in the latter.
Both tumors were partially resected at the same time, and thereafter, recurrence was observed only near S₅ two years and one month after hepatectomy. AFP was also elevated again.
In this report, the discussions were about graphic and pathologic findings of hepatocellular carcinoma strongly indicated multicentric development, and clinical course after hepatectomy.

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