An increase of blood and liver total cholesterol by ethanol did not affect by the joint use of ornithine-aspartate and vitamine B₆.
However, the joint use of ornithine-aspartate and vitamine B₆ had an inhibitory effect on the increase in biosynthesis of fatty acid and on the decrease in biosynthesis of cholesterol by ethanol.
When ornithine-aspartate or vitamine B₆ alone was administered in normal mice, a decrease in the incorporation of acetate-1-¹⁴C into cholesterol and an increase in the incorporation of acetate into fatty acid were seen.
On the metabolic rate of ethanol, the disappearance rate of blood ethanol is more rapid in the ornithine-aspartate treated mice and in mice pretreated with ornithine-aspartate, the metabolic rate of ethanol in liver was higher.
From the above result, it may be said that the joint use of ornithine-aspartate and ornithine-aspartate plus vitamine B₆ normalize partially ethanol induced liver lipid synthesis.

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Interesting results concerning the effect of N-(N-p-carboxyphenylglycyl) aminoacetonitrile (p-CAAN) were obtained from experiments using rats at the time of recovery from chronic liver injury induced by CCl₄. Various metabolic investigations were performed. 1. Lathyrogenic action: Reduction of liver collagen was accelerated and OH-proline in urine was increased.
2. Both hepatic biosynthesis of triglyceride and its transfer from liver to blood were depressed.
3. Transfer of phospholipid from liver to blood was accelerated.
4. It is assumed that abnormalities in red-ox equilibrium of pyridine nucleotide (PN) (relative predominancy of reduced PN) is to be improved.
5. Changes in urinary α-KG and amino-N correspond with the results assumed from increase in body peptide pool containing OH-proline.
Although p-CAAN has been remarked by the lathyrogenic action which is also proven from the above described experimental results, in recent years, steroidal action to depress symptoms of chronic liver diseases has been clinically highlighted. In the near future new clinical application will be expected.
Interesting results concerning the effect of N-(N-p-carboxyphenylglycyl) aminoacetonitrile (p-CAAN) were obtained from experiments using rats at the recovery stage from chronic liver injury induced by CCl4. Various metabolic investigations were performcd. In consequence of lathyrogenic action of p-CAAN, reduction of liver collagen was observed to be accelerated and OH-proline in urine was increased. It was assumed that abnormalities in red-ox equilibrium of pyridine nucleotide (PN) (relative predominancy of reduced PN) is to be improved. This assumption was proven from the variation of the ratio of lactate to pyruvate, of the quantity of α-KG and amino-N in urine. Concerning the lipid metabolism, both intrahepatic biosynthesis of triglyceride and its transfer from liver to blood were depressed, and the transfer of phospholipid from liver to blood was accelerated. Moreover, free fatty acids in liver were clearly reduced and it was supposed that p-CAAN may accelerateoxidation of fatty acids. p-CAAN has been highlighted by the action as lathyrogen, accordingly, new clinical application will be developed in the near future.

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A micromethod was established to quantitate the activity of each of four hexokinase isozylnes in human liver specimens obtained by needle biopsy from patients undergoing peritoneoscopy, using Cellogel membrane electrophoresis. The present study describes the hexokinase isozyme patterns in 25 patients with various liver diseases (acute hepatitis 3, chronic hepatitis 12, liver cirrhosis 7, primary hepatoma 2 and metastatic hepatoma 1). Hepatic glucokinase (hexokinase IV) activity was markedly reduced in patients with postnecrotic liver cirrhosis, hepatoma, acute stage of viral hepatitis and excerbated chronic hepatitis. Patterns of hexokinase I and III differed among these cases: as compared with controls, the activity of hexokinase III was increased (2-5 folds) during acute stage of hepatitis, while that of hexokinase I gradually rose (4-8 folds) with advancement from chronic hepatitis to cirrhosis of the liver and with progression to primary hepatoma (15 folds), suggesting that the rises in III and I activities are possible markers of acute liver damage and chronic progression of liver diseases, respectively.
In conclusion, analysis of hexokinase isozymes is of great value in elucidating the pathophysiology of liver diseases.

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For a basic study on evaluation of therapeutic effects in chronic hapatitis, clinical course was investigated during 3 months, on symptoms, physiological findings, liver function tests and histological findings. The subjects was 75 cases of chronic hepatitis (active form) diagnosed by liver biopsy. Results obtained were as follows.
1) The liver function tests revealed that 68%, 51%, 49%, 40%, 35% and 28% of these cases showed the normal value in albumin, ZST, γ-globulin, TTT, GOT and GPT respectively. 2) There was a close correlation between the ZST values and the degree of focal necrosis, the ZST values and the degree of infiltration of round cells, the albumin values and the degree of focal necrosis, the albumin values and the degree of destruction of limiting plates, the γ-globulin values and the degree of focal necrosis, and the TTT values and the degree of focal necrosis. 3) The circle graph exhibiting the improvement rates of each liver function test determined at the interval of 2 weeks was considered useful for testing the effects of drugs. 4) The degree of histological injuries to the liver was predicted from values of liver function tests using multiple regression analysis, but the multiple correlation coefficient was small and the method was not practical. 5) Canonical correlation analysis indicated that the histologically determined degree of round cell infiltration correlated closely with the albumin values and with the A/G ratios.

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A double blind study for N-[N-(4-carboxyphenyl) glycyl]-aminoacetonitrile (CAAN) was performed for 3 months in 75 cases with chronic hepatitis (active form) showing little tendency to lobular disorganization. Comparing with the placebo-treated group, the following results were obtained.
1) Improvement of the physical findings was noted in the CAAN-treated group (p< 0.05). 2) No improvement of the subjective symptoms was observed. 3) Evaluation on the basis of the degree of abnormality in the liver function tests indicated significant improvement in the γ-GTP values (p<0.01). 4) Analysis of variance with two-way classification forevaluating globally the results of 7 different liver function tests revealed significant difference at the 10th week (p<0.05) and trend difference at the 12th week (p<0.10) after start of the treatment. 5) The improvement rates obtained on the basis of the difference in the degree of histological damages to the liver between the pre- and post-treatment indicated improvement of the damages to the hepatic parenchymatous cells including eosinophilic degeneration (p<0.05) and mobilization of Kupffer's cells (p<0.10) 6) Mild symptoms of the digestive tract were observed in 4 cases as the side reactions to CAAN but these were not so severe that discontinuance of the treatment was not necessary in any of the cases. Global assessment of the results mentioned above leads to the conclusion that CAAN would improve gradually the changing in the parenchyma of the hepatic lobules in chronic hepatitis (active form); the gradualness of improvement is inevitable due to the nature of the disease.

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We report an autopsied case of a 14-year-old boy, who was suffered from HBs antigen positive hepatoma, also producing alpha-l-fetoprotein.
HBs antigen was examined on almost all of his families, and we knew the fact that many HBs antigen positive persons were found out in them. Among HBs antigen positive families, his mother, grandmother, and 7 other relatives were included and all of them had the same subtype, adr.
In addition, autopsied specimens of liver revealed adult type hepatoma, not associated with liver cirrhosis but inactive form of chronic hepatitis.
Judging from the above description, it can be suggested that a persistent HBs antigen infection for 14 years, probably transmitted from his mother, may have induced hepatoma to him.

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