Antibody (anti-pol antibody) against the polymerase gene product of hepatitis B virus (HBV) was determined in HBV infection by solid-phase enzyme immunoassay using synthetic peptides corresponding to the protein coded for by this gene. In acute hepatitis B, anti-pol antibody was detected early in the course in 2 out of 3 patients. In chronic HBV infection, anti-pol antibody was detected more frequently in chronic active hepatitis (17/29, 59%), liver cirrhotics (23/33, 70%) and cirrhotics complicated by hepatocellular carcinoma (18/24, 75%) than asymptomatic carriers (4/19, 21%) and chronic inactive hepatitis (2/7, 29%). Furthermore, titers of anti-pol antibody were higher in liver cirrhotics with and without hepatocellular carcinoma than in chronic active hepatitis. These results indicate that anti-pol antibody is induced in chronic HBV infection as well as acute hepatitis B, and in relation to the progression of liver disease.

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By using dual color analysis, we characterized peripheral blood cell subsets in patients with hepatitis B virus (HBV) induced hepatitis. We found that the imbalance of two CD8 cells, an elevation of CD8⁺CD11^- and a reduction of CD8⁺CD11⁺ cell, exist in fulminant hepatitis but neither acute hepatitis nor chronic active hepatitis. This imbalance of two CD8 cells was only found in acute phase but not in recovery phase. Based on these results, liver infiltrated cells in these patients were also studied by the same method and we found that many of these cells were CD8⁺CD11^-, cytotoxic T cells. These results indicated that CD8⁺CD11^- cells had an important role for the generation of HBV-induced hepatitis.

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The mechanism of increased srum mGOT levels in patients with alcoholic liver disease was studied, using Wistar male rats fed with nutritionally adequate liquid diets containing ethanol as 36% of the total calories. After 6 weeks feeding, mGOT activity in the whole liver and in the liver mitochondoria was significantly elevated in etanol-fed rats compared with control-fed rats. In light microscopic immunohistochemistry, the intensity of mGOT stain was increased in hepatocytes in the centri-lobular area of ethanol-fed rats. In electron microscopic immunohistochemistry, reaction products of mGOT were observed in the mitochondoria both in control-fed and ethanol-fed rats, but they were more prominent in ethanol-fed rats. In vitro study revealed that mGOT leakage from isolated hepatocytes with mildly damaged plasma membrane was increased in ethanol-fed rats than in control-fed rats. These results suggest that the increased serum mGOT level in alcholic liver disease was resulted from the excessive production of mGOT in hepatocytes and the increased leakage across the plasma membrane.

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The total activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and the activity of its active form were measured in hepatocellular carcinoma (HCC) from three patients in comparison with those in liver tissue from five control subjects. The active form significantly increased in HCC (p<0.05). However, the total activity of the reducatse was not significantly different between HCC and normal liver tissue. The rate of sterol biosynthesis significantly increased in HCC (p<0.05). Thus, enhanced synthesis of cholesterol in human HCC seems to result partly from an increase in the active form of the reductase.

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The platelet life span of 16 patients with hepatic cirrhosis and 4 healthy adults were determined with the use of their own ⁵¹Cr labelled platelet. The half life time of platelet of hepatic cirrhosis was significantly shortened to be 2.8±0.4 days compared with 4.3±0.2 days of healthy adults. In the patients with hepatic cirrhosis the increase of platelet pool was demonstrated by the lowering of platelet recovery and platelet consumption. The radioactivity of labelled platelet in the liver was low. Although the ratio of spleen/liver was apparently high, the activity in the spleen was mild to moderate. Therefore, it is considered that not only spleen but also vascular abnormalities such as varices play important roles for the increase of platelet pool of the patients with hepatic cirrhosis.

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The effects of VIP on portal and systemic hemodynamics were investigated in portal hypertension dogs induced by chronic bile duct ligation (CBDL) in comparison with normal dogs.
Portal blood flow volume, portal venous pressure, liver tissue blood flow volume and cardiac output were increased significantly and dose-dependently immediately after bolus injection of VIP, and decreased within 2 to 3 minutes. While in CBDL dogs, these increases were slight but not significant, and they were delayed compared with those in control. VIP decreased systemic vascular resistance significantly, consequently mean blood pressure was decreased in these groups, especially in control groups.
Thus VIP showed less remarkable effect on portal and systemic hemodynamics in CBDL dogs than control. These results suggest that effects of VIP on portal and systemic hemodynamics are different between in CBDL and in normal dogs.
We conclude that VIP affects hepatic hemodynamics not only arterial vessel but portal vein.

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In the study of structural change of liver cirrhosis, the angioarchitecture of mixed nodular cirrhotic liver was investigated by the histological reconstruction method. The ovservation revealed: (1) Preservation of the conducting portion of the portal venous tree, but various changes in fibrous septa after the first-step branches of the parenchymal portion. (2) Ramification and anastomoses of portal and arterial vessels in fibrous septa. These ramifications and anastomoses lead to produce a new inflow system that consists of portal vessel (P), artrial vessel (A), and mixed vessel (MP). This mixed vessel is formed by anastomosis of P with A, and contains portal blood at various ratio. (3) Parenchymal circulation is supported by the branches arising from this inflow system. The contributing ratio to parenchyma, counting up the points where P, MP, and A migrate to sinusoid, are; P:MP:A=75:21:4. After frequent anastomosis with P, MP contains portal blood predominantly at this point. MP supports in maintaining portal blood for parenchymal nutrition, and the stabilization of parenchymal circulation. (4) Formation of a labyrinth-like new drainage system in fibrous septa, which expands in a complicated form, anastomizes with each other, and finally communicates with the branches of hepatic vein at some places. Intra-hepatic shunt blood that flow out from the new inflow system in fibrous septa, is drained through this system.

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We developed a method to determine the plasma disappearance rate (K) and the 15 minute retention rate (R₁₅) of indocyanine green (ICG) using a photopiece applied on a finger tip (finger tip method). In this study we evaluated this method in various liver diseases and compared results with those from the conventional blood sampling method (conventional method). K values of the finger tip method were 0.173±0.03 for the control, 0.123±0.028 in acute hepatitis (AH), 0.115±0.037 in chronic hepatitis (CH) and 0.064±0.03 in liver cirrhosis (LC). R₁₅ values revealed 8.3±4.05% for the control, 17.1±6.87% in AH, 20.4±10.27% in CH and 42.2±16.86% in LC. Both values in CH group showed a significant differences (p<0.05) to values of the control group and LC group, and value of the LC group showed a significant difference to that of control group (p<0.01). Values for k and R₁₅ obtained by the finger piece method correlated significantly with those in the conventional method: y=0.918x-0.003 (r=0.926, p<0.01) for K and y=1.15x+1.196 (r=0.962, p<0.01) for R₁₅. From these results we concluded that the finger piece method is useful to determine K and R₁₅ of ICG.

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We produced diethylnitrosamine induced chronic liver injury in rats. These rats were divided morphologically into two groups: liver fibrosis and liver cirrhosis group. Then we examined cell kinetics of uni- and binucleated hepatocytes after hepatectomy (Hx) using antibromodeoxyuridine monoclonal antibody. The values of labeling indices (LIs) of uninucleated hepatocytes in liver fibrosis group were higher than those in liver cirrhosis one. But the values of LIs of binucleated cells in both groups after Hx were lower than those in normal liver.
From the above results, it is suggested that binucleated hepatocytes in chronic injured liver do not participate in liver regeneration.

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When the heat-killed Propionibacterium acnes (P. acnes) was injected into mouse through tail vein, liver adherent cells including macrophages accumulate in the liver reaching its maximum 7 days later. To study the function of these liver adherent cells, synthesis of interleukin 1 (IL-1) and its regulation by prostaglandin (PG) were investigated. As a result, P. acnes-elicited liver adherent cells produced IL-1 by stimulating with endotoxin lipopolysaccharide (LPS) in a dose-dependent manner. When these cels were treated with PGE₁ or PGE₂, synthesis of IL-1 was significantlly reduced. These result suggested that there are some auto-regulatory mechanisms of mediator which produced by liver macrophages.

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We studied the effects of interleukin-1 (IL-1) on hepatic microsomal metabolizing enzyme activities in Wistar male rats. Intraperitoneal injection of IL-1 (0.4μg/100gBW) significantly depressed the contents of cytochrome P-450 (P-450) By 27%, the activities of NADPH-dependent cytochrome c reductase (cyt c red) by 30%, aniline hydroxylase (AH) by 47% and aminopyrine demetylase (AD) by 31%. In contrast, heme oxygenase (HO) activity was increased by 33%.
Blood level of Al-p was increased, and levels of triglycerides and β-lipoprotein were decreased significantly by IL-1. Complement level (CH₅₀) was not different from those in control rats.
In the present study, we demonstrated the depressive effect of IL-1 on the hepatic drug metabolism. From these data, one must be careful when administering a drug to a patient whose macrophage function is activated and his IL-1 level is high.

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When a small of lipopolysaccharide (LPS) purified from Salmonella minnesota wild, Salmonella minnesota R60 and Salmonella minnesota R345 was intravenously injected with D-galactosamine into rat treated with polymixin B, massive hepatic cell necrosis was induced and most of the rats died within 24 hours. However, when LPS from Salmonella minnesota R5, Salmonella minnesota R7 and lipid A from Salmonella minnesota R595 were administered, the survival rate was much higher and no histological changes in the liver such as necrosis could be seen in any of the rats. In each of the LPS used in this study, the structure of the polysaccharide chain was different, and it decreased in the following order: Salmonella minnesota wild→Salmonella minesota R60→Salmonella minnesota R345→Salmonella minnesota R5→Salmonella minnesota R7→Salmonella minnesota R595. This suggested that the polysaccharide chain of LPS played an important role in the induction of massive hepatic cell necrosis in D-galactosamine induced hepatic injury.

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Five cases of non-a, non-B acute hepatitis were observed among the drug abusers over about one year. They injected stimurant intravenously three of four times per week, using the same syringe. All cases were doagnosed non-A, non-B hepatitis clinically and immuno-serologically. Two cases were biopsied which showed chronic persistent hepatitis and convalescent stage of acute hepatitis.
Viral hepatitis is the most common complication among the drug abusers, especially in the United States. In Japan, this is the first report of an out break of non-A, non-B hepatitis among the drug abusers.

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We reproted two female alcoholics with severe alcoholic hepatitis developed hepato-renal failure.
First case, 46 years old house wife, who admitted with the symptoms of jaundice, ascites and hepatic encephalopathy. Laboratory data showed leukemoid reaction such as 68, 200/mm³ of white blood cell count. She died of renal failure on 18th day after admission in spite of the treatments of glucagon-insulin therapy and plasm exchange.
Second case, 55 year old house wife, was admitted with the symptoms of jaundice and hepatic encephalopathy. She was treated with BCAA-rich diet and prednisolone. However she died of renal failure on 17th day after admission.
Histological findings of the two autopsied cases showed typical alcohlic hepatitis acompanied with a great number of alcoholic hyalin.

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