Although there has been considerable debate as to the pathways of alcohol metabolism, It still can be stated with confidence that the main enzyme responsible for ethanol oxidation is alcohol dehydrogenase. This enzyme is found in the cytoplasm of the liver cell. There are two other mechanisms for the oxidation of alcohol: 1) catalase and catalatic peroxidation; and 2) microsomal ethanol oxidation. Many laboratories including our own have attempted to determine the mechanism of microsomal ethanol oxidation and whether this system has any physiologic or clinical significance in the overall metabolism of alcohol. Most of the evidence that we have obtained would suggest that microsomal ethanol oxidation which can be demonstrated in vitro is the net result of two enzyme reactions: 1) NADPH oxidase and 2) catalase. The interactions of these two enzymes lead to the production of hydrogen peroxide which in turn serves to oxidize ethanol to acetaldehyde. Evidence for this concept as an explanation of microsomal ethanol oxidation will be presented.
One of the effects of alcohol is the production of a fatty liver. Fatty liver can be produced by: 1) increased fatty acid synthesis, 2) decreased fatty acid oxidation, 3) increased fatty acid esterification, 4) decreased formation of the apoproteins of lipoproteins, 5) increased mobilization of fatty acids to the liver and 6) decreased release of lipoproteins from the liver. Alcohol affects many of these processes. Much of the available evidence indicates, however, that decreased fatty acid oxidation is probably the most significant factor in leading to the production of the fatty liver produced by alcohol. In general the fat in the liver is present in the form of triglyceride and is present in two types of particles, a small 30-80A particle and the other>200A. The smaller particle represents the lipoproteins which are being prepared for export. The larger particles represent the lipid being accumulated in the liver.
One of the features of alcohol on the liver is the production of hyperlipemia. This appears to be due to increased synthesis of lipoproteins by the liver and is most common in individuals who already have an elevated triglyceride level especially those with an underlying defect in type IV hyperlipoproteinemia.
Hypoglycemia occurs with alcohol but only when the glycogen stores of the liver have been depleted due to poor nutrition or fasting. The other metabolic effects of the liver will be discussed.
Finally in addition to the effects on the liver we have come to learn of important actions of alcohol on the intestine. These include: 1) increase in lipid synthesis by the intestine which contributes to the fatty liver, 2) decreased vitamin B₁₂ absorption, 3) decreased sugar and amino acid transport and 4) decrease in calcium absorption. These effects of alcohol on the intestine may contribute to the impaired nutrition seen in alcoholic subjects.

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Nineteen liver biopsy specimens (8.9%) from 19 cases exhibited abnormal interlobular bile duct epithelium among 214 biopsy specimens from 188 patients with acute viral hepatitis.
Abnormal bile ducts had swollen, flat or columnar epithelial cells with karyopyknosis or karyorrhexis. The cytoplasm of some epithelial cells was deeply stained on eosin. Vacuolized epithelial cells were seen in 15 cases. In all 19 cases the epithelium was infiltrated by inflammatory cells and the epithelium was partly multilayered in 6 cases. The lumen was obstructed by swollen epithelial cells in 3 cases and cellular debris was occasionally found in it. Rupture of the walls of the bile ducts was noted in 6 cases.
The portal tracts containing abnormal bile ducts were enlarged and often infiltrated by lymphocytes which occasionally formed follicles without germinal center. Granuloma was never found.

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The localisation and the distribution patterns of Hepatitis B Antigen in the liver of patients with various forms of hepatitis were examined by direct immunofluorescent antibody technique.
Specific fluorescence was observed mainly in the cytoplasma of liver cells.
Four distribution patterns of fluorescence-positive cells were observed, that is;
I . Solitary type.
II. Focal type.
III. Dissminated type.
IV. Lobular type.
These patterns correlated well with the histological diagnosis of hepatitis, namely, the type of distribution pattern tended to change from I to IV as the hepatitis progressed to more chronic and severer form.
It was suggested that the examination of HB Ag in the liver by immunofluorescrence gave an important information about the progression of hepatitis B.

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To investigate the influence of alcohol on liver diseases, 116 patients without complication who were alcoholics and drank more than 80g per day during at least two years were selected.
1) Alcoholics are 13.2% of 1, 239 patients diagnosed by liver biopsy from 1960 to 1972.
2) Five types of liver lesions were classified histologically-Slightly Injured Type (19.8%), Fatty Liver (10.3%), Fibrosis Type (23.3%), Early Stage of Cirrhosis (13.8%) and Cirrhosis (32.8%) respectively.
3) No relation could be seen between quantity of alcohol and hepatic lesions. On the other hand in the cases drank more than 21 years, early stage of cirrhosis and cirrhosis were significantly frequent.
4) In alcoholics, most of the liver function tests were abnormal and GOT/GPT was usually over 1. Moreover, elevation of γ-GTP and iron deposition were noticed.
5) According to histological classification of liver cirrhosis after MIYAKE, Type A' was more frequently encountered in alcoholics than in non-alcoholics.

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Splenic shadow appearances on hepato-scintigram were high in liver cirrhosis, chronic hepatitis and acute hepatitis in this order and they had close correlativity with serum γ-globulin level, however, no relations with rectal cappillary pressure, which is said one of the indicator of hemodynamic disturbance in liver disorders. Splenectomy, performed patients with liver cirrhosis, resulted in hypergammaglobulinemia. Experimental studies, using albino rabbits, showed that the spleen weight, obtained after the administration of several hepato-toxic substances, had intimate relations with serum γ-globulin levels. Furthermore, in a group in which splenectomy was performed after the development of hypergammaglobulinemia, serum γ-globulin level elevated reboundedly despite transient decrease in comparison with extremely low level of serum γ-globulin in a group in which splenectomized before sensitization.
These results may suggest that splenomegaly in liver disease is not only the result from hemodynamic disturbance, but one of the important reacting place where many factors including antigen antibody reaction are entangled.

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This study has been carried out to evaluate quantitatively the liver function test values for the last month of toxemia of pregnancy in comparison with those for the last month of normal pregnancy.
The results were as follows:
1) The differences in average for total protein, S-GOT and S-GPT (Karmen u.) have been found insignificant between toxemia and normal pregnancy.
2) When alkaline phosphatase level (Bessey-Lowry u.) rises to the range of 6.27 to 10.08 units, toxemia of pregnancy is suggested, and above 10.08 units, complications, probably of the liver, may be suggested.
3) The average for serum total cholesterol was significantly lower in toxemia than in normal pregnancy. Any pregnant women whose total cholesterol is below 155.1mg/100ml would have some abnormalities, possibly of the liver.
4) Zinc turbidity test declines slowly within the normal value range during normal gestation. Therefore, if a high figure of the test is seen in the last trimester, we should suspect some liver disorder.
5) The average for A/G ratio was higher in toxemia than in normal pregnancy.

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The progress of chemotherapeutics brought a remarkable proceeding in tuberculosis therapy, but on the contrary some side-effects of anti-tuberculosis drugs, particularly its hepatotoxic effect, were reported since many years ago.
The case reported is 46 year-old female, treated with ethionamide orally. About three months later, the administration of ethionamide, while the patient was suffered from jaundice and subsequently hepatic coma, exchange blood transfusion (4l of fresh blood) was tried twice for her. Despite this treatment showed remarkable improvement of disturbance of consciousness as well as in liver function test, the patient was finally died due to hepatic failure several days later.
The presented report dicussed on clinical feature and pathological finding of a case of ethionamide-induced hepatic necrosis and on therapeutic evaluation of exchange blood transfusion therapy.

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Two cases of primary biliary cirrhosis were studied. Case 1, 51 years old woman, this patient had been presented with history of pruritus for 6 years and jaundice for 1 year. Case 2, 67 years old woman, this patient was found the abnormality of liver function on medical examination without subjective symptoms. In both cases laboratory examination revealed marked elevation of serum bilirubin, alkaline phosphatase and cholcsterol and modelate elevation of GOT, GPT and γ-globulin. We hadn't found of findings of obstruction of extrahepatic bile ducts, in spite of examination of explorative laparotomy and direct cholecystography. The findings of wedge biopsies of liver were cholestasis, extended portal tracts with infiltration of lymphocytes and plasma cells and destruction of epitheliums of interlobular bile ducts. Case 1, she died 2 years after admission and in autopsy findings the liver was 1100g and histological diagnosis was biliary cirrhosis. Case 2, she survives.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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