Clinical and laboratory observation were performed in 13 cases with infectious mononucleosis hepatitis (group I) and the results were compared with those in 23 cases of acute viral hepatitis type A (group A). The diagnosis in group I was confirmed by the tests for heterophil antibody, IgM antibody to viral capsid antigen of EB virus and IgG antibody to its early antigen. There was no difference in sex and age of both groups. In group I the specific clinical symptoms and signs were sore throat, headache, cough, lymphnode swelling, tonsillitis and eruption, and icterus was not common compared with group A.
The ratio of LDH, γ-GTP, LAP and ALP to GPT were significantly higher in group I. With respect to histological findings in convalescent stage, lipofuscin deposits and sinusoidal mononuclear cell infiltration were apparently observed in group I, while bile pigment deposition and sinusoidal neutrocyte infiltration were common in group A. As mentioned above, we could clarify several differences between group I and group A, which is useful in differential diagnosis. However, it is important to differentiate both group actively with the specific test for the antibodies against EB virus and HA virus, because some features such as fever, prolonged elevation of TTT, atypical lymphocyte in peripheral blood were observed in both groups.

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Fluctuation of the serum transaminase activity were determined and classified into the following four types for 51 cases of chronic non-transfusion, non-B hepatitis, for which we were able to perform hepatic biopsy on at least two separate occasion and to follow up for not less than 5 years. Histologically, 50 of 10 cases (50.0%) of Type I showed aggravation, while progress of the disease was observed in 17 of 18 Type II cases (94.4%) in Type III, 9 of 12 cases (75.0%) showed aggravation, and in Type IV, the disease exacerbated in 7 in 11 cases (63.6%). Progress of the disease was evident in 31 of 32 cases (96.8%) with high serum γ-GTP levels, while aggravation was noted only in 7 of 19 cases, or 36.8%, of normal γ-GTP levels, and thus there was a statistically singificant difference between the two groups in this respect (p<0.025).

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An immunopotentiator, OK-432 which is known to have interferon inducing activity, was administered intramuscularly for 3 months and more to patients suffering from HBeAg positive chronic hepatitis. The therapeutic effect of the drug was evaluated mainly by changes in HBeAg/anti-HBe system in the patients treated with OK-432 compared to untreated historical controls.
Results: In the OK-432 group, over an average observation period of 20.1 months HBeAg disappeared in 27(64.3%) out of 42 patients, and seroconversion from HBeAg to anti-HBe occurred in 14 (33.3%) of the patients. In the untreated control group, over an average observation period of 32.3 months HBeAg disappeared in 23(30.6%) out of 75 patients, and seroconversion from HBeAg to antiHBe occurred in 13(17.3%) of the patients.
These results indicate that OK-432 treatment improved the HBeAg/anti-HBe system in patients with HBeAg positive chronic hepatitis.

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There are many hypotheses in the mechanism of hyperglucagonemia in humans during cirrhosis or hepatic coma. We studied the effect of receptor blokers to autonomic nervous system on level of plasma glucagon immunoreactivity (GI) in rats given carbon tetra chloride. Administration of propranolol, a betaadrenergic antagoinst, significantly lowered the high level of plasma GI induced by carbon tetrachloride in rats to about 60% of that of controls (p<0.01). Atropine, an anticholinergic agent, also depressed the hyperglucagonemia to about 55% of not-treated animals (p<0.01). The minimum doses of propranolol and atropine to rats on depression of the hyperglucagonemia appeared to be 0.2 and 0.5mg per kg body weight, respectively. On the other hand, phentolamine, an alpha-adrenergic blocker, did not influence the hyperglucagonemia induced by carbon tetrachloride. The concentrations of glucose, immunoreactive insulin, GOT and GPT in plasma were not affected by both propranolol and atropine and these two blockades showed no changes in plasma GI level in normal rats. These results suggest that beta-receptor of sympathetic and cholinergic nervous system might be involved in the process of hyperglucagonemia induced by hepatic failure such as carbon tetrachloride.

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We examined the effects of glucose administration on the recovery of galactosamine induced acute liver injury of rats, by giving either orally or subcutaneously. The survival rate was higher in oral glucose administration group (oral group) than in subcutaneous glucose administration group (subcut. group). Histologically the liver repaired in oral group but not in subcut. group, at 72 hours after galactosamine treatment. The difference in gluose concentration between portal and peripheral vein was significantly higher in oral group than in subcut. group, suggesting that oral glucose administration rather than subcutaneous increased hepatic glucose uptake. Regional hepatic blood volume and oxygen consumption measured by reflectance spectrophotometry and ATP level in the liver were increased by oral but not by subcutaneous glucose administration. The results suggest that oral glucose administration is more effective on the recovery of galactosamine induced acute liver injury than subcutaneous glucose administration.

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The natural killer (NK) activity of perpheral blood lymphocytes (PBL) from patients with various chronic liver diseases and healthy controls were examined using 5-hr 51Cr-releasing cytotocicity assay against K562 24-hr after 100μg/ml polyinosinic: polycytidylic acid (poly I:C) and 500IU/ml interferon (IFN) were added to PBL.
The level of endogenous NK (E-NK) decreased in the order of healthy persons (26 cases), patients with chronic hepatitis (CH) (26), liver cirrhosis (LC) (39) and hepatic carcinoma (HCC) (18). Of note is the fact that the level was low in cases of HCC (p=0.0352). There was a significant decrease in revised NK activity in LC (p=0.0303) and HCC (p=0.0032) as compared with normal controls. The addition of poly I:C and IFN increased NK activity (p=0.0000) as compared with that of E-NK.

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The etiology of idiopathic portal hypertension (IPH) is not known. To obtein clues to the etiology, we attempted to make a hepatic lesion similar to that of IPH by repeated infusion of aggregate of nonpathogenic Escherichia coli (E. coli) and its rabbit antiserum dilectly into the portal vein in rabbits sensitized with E. coli.
In the treated rabbits, liver histology showed dense fibrosis in the portal area, aberrant vasculature around the portal area and narrowing and compression of peripheral portal vein. Portal pressure was elevated in many of them. Middle sized portal branches were decreased number and had diminished diameter as studied on portograms.
These changes closely mimic those seen in human IPH, and the possibility is suggested that infection of E. coli for long time and the entrance of antigen such as bacteria from intestine into the portal system may play a role in the development of IPH.

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Preventive effects of a vasoactive drug on the development of chronic liver injury were investigated. Male Wistar rats, approximately 170g of body weight, were used in this experiment. Neurotropin (NSP), an ectract from inflammatory skin tissues of rabbits inoculated with vaccinia virus, was used as the vasoactive agent. In animals subjected to condecutive CCL4 exposure, cirrhosis was developed by 13 weeks, while the animals treated with NSP showed no cirrhotic changes. In rats fed a diet containing 0.06% 3'-methyl-4-diethylaminoazobenzene (3'-Me-DAB) for 13 weeks, liver cell carcinoma and/or cholangio-cellular carcinoma were induced within the following 23 weeks. The animals treated with NSP, on the contrary, showed only hyperplastic change of bile duce and/or occasional small cholangiocellular carcinoma. The rats to which NSP was administered from the 4th week after the start of the carcinogen exposure, exhibited no tumor formation. It is suggested that vasoactive drug has ameliorative efffects on chronic liver injuries.

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Liver consistency (LC) was measured in vivo (n=52) at laparotomy and in vitro (n=24) using hepatectomy specimens by the specially devised instrument. It was consisted of a needle equipped with a latex microballoon, connecting to a strain gauge via polyethylene tube. The microballoon was inserted into the liver parenchyma and then Pressure (P)-Volume (V) curve was recorded under a constant saline infusion. LC was defined by the linear slope of pressure rise, Δ1P/ΔV (cmH2O).
LC, measured thus, showed a high degree of agreement with each histopathologic grading of the liver, and strongly correlated with morphometrically estimated collagen content of the liver (r=0.82, p<0.001). Among various items of liver function tests, ICG retention rate correlated with LC (r=0.68, p<0.001) more significantly than any other tests including albumin, prothrombin time, gamma-globulin and ZTT.
The present study has indicated that LC measurement by this technique is useful in quantitating the degree of hepatic fibrosis.

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Pre and post-operative changes of the hemostatic functions in 15 patients with portal hypertension were studied, with reference to liver cirrhosis and postoperative jaundice. The tests included APTT (sec), PT (%), fibrinogen (Fbg) (mg/dl), FDP (μg/ml), plasma antithrombin III (AT III)·serum plasminogen (Plg)·α1 antitrypsin(α1 AT)·α2 macroglobulin (α2 M) (mg/dl), α2 plasmin inhibitor (α2 PI) and platelet (Plat) (104/mm3). The results indicate the pathophysiological and clinical significances as follows: 1) All patients were in the hypocoagulable state, with or without liver cirrhosis. 2) In liver cirrhotic groups, on the preoperative evaluations, almost of those with APTT≥44, PT≤60, Fbg≤170, AT≤15 and α2 PI≤65 were prone to be in jaundice, and those with PT≤50, AT III≤12 and Plg≤5 were died, postoperatively. 3) Postoperatively, hemostatic functions returned to normal in almost all tests in the non-cirrhotic group, but only in APTT, Fbg and Plat in the cirrhotic ones. 4) Hypercoagulability which were seen in the patients postoperatively were prominent in non-cirrhotic groups. 5) The hemostatic abnormalities in the patients with postoperative jaundice and hepatic failure were not DIC but disorders in the production of the hemostatic elements. 6) Post-operative changes of it reflect the progression and prognosis of hepatic failure.

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DNA content of hepatocellular nuclei was determined by microphotometry using UMSP-I (Zeiss) in 9 autopsy livers with cirrhosis in which 4 cases had hepatoma and the remaining 5 had not, in order to analyze the behavior of liver tissue in the background of canceration. The average DNA density of a nucleus was found to be reversely proportional to nuclear volume. In the presence of hepatoma the mean DNA density of a hepatocellular nucleus was significantly higher than in cirrhosis not associated with hepatoma. This result substantiated on cytological level our previous observation that hyperplastic areas were contained in cirrhotic livers harboring hepatoma and were characterized by clumps of hepatocytes with uniformly small nucleus, and indicated the predominance of extremely DNA-dense nuclei in such areas. Probably these cellular features are an expression of proliferating parenchyma. which may correspond to a state preceding the development of hepatoma.

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Binding ability of radiolabeled antibodies against CEA and AFP with human hepatoma producing CEA and AFP was investigated.
Cultured human hepatoma producing CEA and AFP was used for in vitro study, and the human hepatoma growing in nude mice was used for in vivo study. Binding ability was assessed by microautoradiography in vitro, and by scintiscanning, autoradiography and organ radioactivity counting in vivo
In vivo assays such as scintiscanning and radioactivity counting showed significantly higher accumulation of radioactive antibody in the tumor 7 days after administration of radiolabeled anti-CEA antibody. Silver grains, which represent the localization of anti-CEA antibody on the microautoradiograph, were observed on tumor cells in vitro and in vivo.
Binding of anti-AFP antibody with cultured tumor cell was not observed. Radioactivity counting showed the increased uptake of anti-AFP antibody in the tumor. Microautoradiograph, however, showedthat this accumulation was mainly observed in the intercellular space and necrotic tissue.

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The reticuloendothelial phagocytic activity was measured using liver slice bioassay and I¹³¹ labeled lipid emulsion method among the following three groups: normal male Wistar rats, 68% hepatectomized rats with and without ATP-MgCl₂ treatment at 24 hours following hepatectomy. Comparing to nonhepatectomized normal rats, opsonic activity was increased and Kupffer cell activity was decreased among the hepatectomized rats. Phagocytic index was impaired following hepatectomy but returned to near normal value with ATP-MgCl₂ administration following hepatectomy. The uptake of lipid emulsion per gram of liver tissue was decreased following hepatectomy but remained at the almost normal value with ATP-MgCl₂ administration.
Increased pulmonary accumulation of lipid emulsion in hepatectomized rats was normalized by ATP-MgCl₂ administration. These results indicate that the depression of phagocytic activity following massive hepatectomy is due to the depression of Kupffer cell activity and that the depression is not due to the depleted opsonic protein.
The results also indicate that the ATP-MgCl₂ administration has a salutary effect on the depressed phagocytic activity of the hepatic remnant, and suggest that ATP-MgCl2 administration may prevent the posthepatectomy pulmonary complication induced by depressed phagocytic activity.

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Gianotti's disease (papular acrodermatitis) is characterized by erythematous papula localized on extremities, hips and face in children and by liver function disorders. Recent study has successively elucidated the fact that the disease is associated with hepatitis B virus infection and high frequency of ayw among HBs subtypes. In the present paper we report an adult case of Gianotti's disease with HBs antigenemia (subtype adw).
A 27 year-old man was admitted to Toyama Medical & Pharmaceutical University Hospital with complaints of systemic eruption with itching, after the appearance of general fatigue and epigastralgia. The particular eruption appeared initially at bilateral wrists and spreaded upward to upper extremities and trunk symmetrically.
On admission the conjunctiva bulbi and skin were icteric. He was found to have hepatomegaly and papular erythematous lesions over the arms, legs and chest symmetrically. Left inguinal lymphadenopathy was found during the period of hospitalization.
Laboratory data on admission revealed elevated transaminases, increased serum immune complex and HBs antigenemia. Subtype of HBs antigen was adw.
Biospy specimen of the liver showed characteristic features of type B acute viral hepatitis and that of papular erythematous lesions revealed chronic dermatitis. We failed to demonstrate HBV-associated antigens, complements and immunoglobulins in skin lesions by immunohistochemical methods.
Pruritis, jaundice and eruption disappeaed on the 7th, 16th, and 24th hospital day, respectively. The liver function was normalized and HBs antigenemia disappeared 3 weeks after the admission.

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