The cytochrome P-450 in liver microsome catalyzes the drug oxidation by using oxygen and NADPH. We have investigated the mechanism on the inhibition of cytochrome P-450-dependent mixed function oxidation by ethanol.
NADPH oxidation decreased with increasing ethanol concentration in liver microsomes. Ethanol induced a reverse type I binding spectrum, and competitively inhibited the binding of hexobarbital to liver microsome due to the displacement of the endogeneous substrate.
The NADPH-dependent reduction of liver microsomal cytochrome P-450 was biphasic and composed of two concurrent first-order reactions. The addition of hexobarbital increased the both rate constant for the fast and slow phase. The rate constant for the fast phase was decreased by the addition of ethanol, but the rate constant for the slow phase remained unchanged. Therefore, the inhibition of mixed function oxidation by ethanol may be due partly to the decrease of NADPH-cytochrome P-450 reductase activity resulting from the decrease of substrates bound to cytochrome P-450 by ethanol.

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8 patients surviving subacute hepatic necrosis and three patients with classical acute viral hepatitis in needle biopsy specimens despite of fulminant hepatic episode were subjected in order to study on the regenerating and/or regenerated hepatocytes. Three types in these hepatocytes were founded in the electron microscopic study.
The first type; the hepatocytes with intense staining of the cytoplasma with eosin showed the remarkable increase of mitochondrion and rough surfaced endoplasmic reticulum in the complex structure. The second; the hepatocytes with the clear cytoplasma in H-E staining revealed the proliferation of smooth surfaced endoplasmic reticulum. These two types of hepatocytes showed thickening of cell plates and their nodules exserted pressure on the adjacent mesenchyma. The last; the hepatocytes with little degenerative figures were noticed among rosette forming hepatocytes in the vicinity of the necrotic areas. These cells were thought to be regenerated, as compared with adjacent hepatocytes.

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When the blood serum from a patient with liver cirrhosis was fractionated by a Sephadex G-75 gel filtration and the certain fraction was injected into mesenteric vein of rats, a marked reduction of bile flow was seen. Similar results were obtained when peripheral lymphocytes from the patient were stimulated with HBs antigen or liver specific lipoprotein in vitro and the certain fraction which was fractionated with a Sephadex G-75 gel filtration was injected into mesenteric vein of rats. Histologically, a dilated bile canaliculus with the diminution of microvilli and increased vesicles around the dilated canaliculi were observed by an electron microscopy after injection of culture supernatant fraction into rats.
These results strongly suggest that not only the sensitized lymphocytes produce the cholestatic factor (factors) which causes the intrahepatic cholestasis, but also this factor involves significantly in the pathogenesis or intrahepatic cholestasis which observes in the patient with liver cirrhosis.

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The cytotoxic effect of peripheral blood lymphocytes from patients with various liver diseases against T-24 cells and Chang cells was studied using a ⁵¹chromium release assay. The mean %cytotoxicity of 32 control subjects against T-24 cells was 7.3±4.2% (mean±SD). The mean %cytotoxicity of 25 patients with chronic active hepatitis, 20 patients with liver cirrhosis and 15 patients with hepatoma against T-24 cells was 5.8±3.5%, 7.0±4.1% and 6.7±3.8% retrospectively. Each value was not so different from that of the control subjects. But the cytotoxicity of lymphocytes from 4 patients with the end stage of hepatoma was significantly decreased. The cytotoxicity of lymphocytes on the acute stage of acute hepatitis was significantly decreased, but improved in the convalescent stage. The results mentioned above were almost as same as against Chang cells. The cytotoxicity of lymphocytes was enhanced by addition of interferon. Therefore, it was presumed that the cytotoxicity might represent the natural killer activity of lymphocytes. A significant reduction of the cytotoxicity of normal lymphocytes was noted when sera from chronic active hepatitis, liver cirrhosis and hepatoma patients was added.

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In order to elucidate growth factors of the human fetal liver, intrahepatic portal blood supply and changes of liver weight of right and left lobes during the development were investigated with relation to development of portal organs, especially pancreatic islet, using 81 fetuses.
In the human fetal liver, the left lobe is supplied by the umbilical blood flow and the right lobe by the portal blood flow. When the fetus was at 3 months' pregnancy, liver weight of right lobe was about half that of left lobe. However, when the fetus was at 7 months' pregnancy, liver weight of both lobes was almost equal depending on marked increase of right lobe weight after 5 months' pregnancy, accompanied by development and maturation of the pancreatic islet, particularly of the B cell.
These results suggest that portal factors, including pancreatic hormones, accelerate the development of the human fetal liver, especially the right lobe.

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In order to clarify the pathogenesis of hepatic coma, the effects of ammonia on pancreatic glucagon, insulin and blood glucose were studied in the patients with portal hypertension.
After an oral loading of ammonium chloride, plasma ammonia, glucagon, S-OCT and S-GOT increased remarkably in the patients with liver cirrhosis compared to those in the patients with hepatic fibrosis. In the cirrhotic patients, the basal concentration of glucagon were three times of that in the patients with hepatic fibrosis and the plasma glucagon increased as much as two times of the basal glucagon after 2 hours of an oral administration of ammonium chloride, while essentially unchanged in the patients with hepatic fibrosis. Glucagon concentration correlate closely to the degree of hyperammonemia in cirrhosis. However, insulin concentration and blood glucose were unchanged after an oral ammonia administration.
It is suggested that blood ammonia, elevated in cirrhosis, stimulates pancreatic glucagon secretion.

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Results of 60 cases of resected hepatocellular carcinoma (HCC) were analyzed with respect to operative risk, postoperative complication and survival after surgery. Five-, three-, and one-year survival rates of the patient were 8, 34 and 52 percent, respectively. There was a patient of longest survival who is still living eight-and-a-half years after extended right hepatectomy. The two major causes of death after surgery were reccurence of the cancer and hepatic failur. In cases with liver cirrhosis, the cause of late death was twice more frequently by hepatic failure than reccurent carcinoma. Considering this major risk factor, liver cirrhosis, we had developed a useful method to estimate the remaining hepatic function preoperatively.
Our experiences showed that complete removal of HCC with the efforts to save the noncancerous hepatic tissue as much as possible is essential. As the results of the efforts with this principle, two- and one-year survival rates were improved to 67 and 88 percent respectively in recent two years.

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We reported two cases of acute viral hepatitis of non-A, non-B type in a family. A mother in a family, 47 years old, was diagnosed as sporadic non-A, non-B acute hepatitis and was admitted in a hospital. One of her daughters, 22 years old, had been taking care of the patient at home before and in the hospital after admission. This daughter developed acute viral hepatitis of non-A, non-B type 3 months after the onset of her mother's illness. The other members of this family, husband of the propositus case and the younger daughter, showed no sign of hepatitis and revealed no abnormalities in their blood chemistries. Forthermore, no epidemic outbreak of viral hepatitis could be obserbed around this family. So that the mode of the contraction of non-A, non-B hepatitis in this affected daughter was thought to be due to the intimate personal contact with her mother.

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An autopsy case of 16-year-old female of Wilson's disease with features similar to those of chronic active hepatitis was reported.
Seven years before her death, she was suffered from general malaise, fever, vomiting, and jaundice, and suspected to be acute hepatitis. Then, hypoceruloplasminemia and Kayser-Fleischer ring were found, and diagnosed as Wilson's disease. At 15 years old, she had acute hepatitis-like symptom again, and died of excessive hemorrhage due to duodenal perforation.
Autopsy revealed the liver with severe inflammatory cell infiltration, severe degeneration and regeneration of the hepatocytes, and submassive necrosis, indistinguishable from chronic active hepatitis. Hepatic copper concentration was elevated (520μg/g dry weight by atomic absorption method). This case had no genetic background.
Whether hepatic morphological changes are only due to copper toxicity or not, is discussed.

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Two cases of familial Sjögren's syndrome associated with chronic active 'lupoid' hepatitis were reported.
A 48-year-old female, case 1, admitted for the complaints of easy fatigability, anorexia, and dry mouth. Seroimmunologic and histological examination revealed typical chronic active 'lupoid' hepatitis associated with Sjögren's syndrome.
By the survey of familial abnormality, case 2, a 45-year-old younger sister of case 1 provided the clinical feature of Sjögren's syndrome without liver disease.
Familial Sjögren's syndrome is rare and eighteen families were reported until now. In those reports, systemic lupus erythematosus, progressive systemic sclerosis, rheumatoid arthritis, sclerosing cholangitis, and Hashimoto's thyroiditis are associated with Sjögren's syndrome, the association of chronic active 'lupoid' hepatitis reported here is not described.

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A 50-year-old man was admitted to our hospital on August 1, 1980 because of reccurent attacks of unconsciousness for five years. On physical examination, a finger tremor and accentuation of the tendon reflex were noted. Laboratory findings showed pronounced elevation of serum ammonia (289.1μg/dl) and ICG retension (20.8%, 15min). θ wave was dominant on EEG. Selective celiac and superior mesenteric arteriography revealed rapid filling of the intrahepatic aneurysm which was connected to the portal vein via a fistula (A-P shunt) and collaterals from inferior mesenteric vein to inferior vena cava were observed. Partial hepatectomy including the aneurysm and the ligation of the enlarged inferior mesenteric vein resulted in the disappearance of a finger tremor and an accentuation of tendon reflex as well as the disappearance of the attacks of unconsciousness. Serum ammonia, ICG, BCAA/AAA ratio, EEG and blood frow of the liver were all improved remarkably. It was concluded that, in this case, the rupture of aneurysm of hepatic artery into portal vein caused an A-P shunt with portal hypertension which was followed by the development of collaterals into inferior vena cava and finally resulted in the portal systemic encephalopathy.

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An unusual case of hepatocerebral syndrome was described. A 28-year-old man consulted an ophthalmologist because of inability to recognize traffic signals and letters on television, namely a certain type of visual agnosia. He was referred to internists and diagnosed to have liver disease with HBsAg. Electroencephalography showed general slow waves and the typical triphasic ones in the occipital lead. At the same time hyperammonemia and endotoxinemia were observed. Laparoscopy revealed coarse nodular cirrhosis, splenomegaly, and marked venous dilatation in the abdominal organs. This central nervous system manifestation was considered to be due to portal systemic encephalopathy. He improved on dietary protein restriction, antibiotics, lactulose, and other supporting treatments, and returned to work.

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Polycystic liver is relatively rare disease, about 200 cases being reported in Japan till 1975. We report our 14 cases including a rare case (case 11) of non-parasitic polycystic liver disease complicated with calcification.
Our 14 cases were between 43 and 80 years of age, four times more in females than in males. Chief complaints were abdominal pain, meteorism, general malaise etc. and physical examination showed hepatomegaly, palpable tumor and palpable kidney. Three cases had impaired liver function tests but their degree of abnormality was slight. We studied them with hepatic scintigram, peritoneoscopic examination etc. and 43% (6 cases) were detected to have renal cysts. Case 2 was advanced cancer of liver and pancreas and carcinoma arising from the liver cysts was suspected. A half (7 cases) was treated medically and the other half, surgically (cystectomy and so on).
Case 11 (a 65 year-old female) was admitted to our hospital with chief complaint of meteorism, ascites and hepatomegaly. CT scanning, operation (fenestration of cysts) and histological examination revealed that this case was a calcified nonparasitic polycystic liver disease. Only two of such cases were reported in 1977 by Kutcher, R et al.

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