Rate of oxygen consumption of the liver slices from 169 patients with various liver diseases and 4 patients with normal liver were measured in the O₂-electrode apparatus in which cellulose diacetate (7.5%) was coated as a membrane. The respiratory activities of the livers in the presence and absence of added substrates for respiration were decreasing with progress of liver diseases, as expressed per gr of liver wet weight. The activities were also greatly in fluenced by glucose tolerance. No liver function tests except OGTT significantly correlated with hepatic respiratory activities. The local blood volume in the livers, measured by in vivo reflectance spectrophotometry, did not necessarily correlate with the measured respiratory activities. It is concluded that the hepatic respiratory activities correlate with not only the local blood flow (O₂-supply) in the liver but also glucose metabolism.

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Clinical significance of hepatocellular lipolysosomes was studied in biopsy specimens. Lipolysosomes were found in 16 of 22 patients suffering from various liver diseases and the proportion of lipolysosomes to storage lipid droplets ranging from 0 to 9%. Generally lipolysosomes increased in number with severity of fatty change of the liver. In chronic liver diseases, the proportion of lipolysosomes to storage lipid droplets were correlated to aging; it was low in the young patients, while it was high in aged. The increased proportion suggests an impaired function of lysosomes with aging, resulting in lipid-laden variants. There was a tendency that serum cholesterol reflected the proportion of lipolysosomes in the liver but dietary cholesterol had no effect on the proportion. This means that dietary cholesterol is less significant in the pathogenesis of the fatty livers in Japan.

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To ascertain a promoting factor of glucose intolerance and abnormal insulin response in liver disease, insulin binding to peripheral mononuclear cells was compared with results of 100g-OGTT and insulin sensitivity index (ISI). A half ng per ml of ¹²⁵I-insulin specific binding to 10⁷ cells was tested in 14 normal subjects and 49 with liver disease.
In liver disease, peripheral insulin activity (A) and ISI were decreased. Insulin binding in normal was 1.03±0.57%, and decreased significantly in liver disease (p<0.01). Scatchard plots revealed that the decrease in liver disease was owing mainly to reduced binding sites. Significant correations were found between insulin binding and ISI or A.
In conclusion, the reduced insulin receptor may have a significant role for the progression of glucose intolerance in liver disease.

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We searched for antigen-antibody systems associated with hepatitis viruses in sporadic acute hepatitis observed in the internal department of Nagoya city Institute of Higashi Hospital from June, 1976 to December, 1979. We then classified 72 cases of those hepatitis to hepatitis A, hepatitis B, and non A, non B hepatitis, and compared especially their frequency and clinical course.
The frequency of each hepatitis was hepatitis A: 30.6%, hepatitis B: 25.0%, non A, non B hepatitis: 44.4%.
Clinical symptoms, especially subjective symptoms passed by less seriously in the order of hepatitis A, hepatitis B, and non A, non B hepatitis.
With respect to prognosis, all 22 case of hepatitis A healed well without persistent symptoms.
In hepatitis B, one case died of subactue hepatitis, but other 17 cases healed well without shifting to chronic hepatitis or continuous infection. Non A, non B hepatitis passed by less seriously in clinical symptoms, however 7 cases out of 32 (21.9%) shifting to persistent and chronic hepatitis, but we observed no case of death.
Atypical lymphocytes was observed in hepatitis A, and some non A, non B hepatitis in peripheral blood pictures.

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Clinical and laboratory observations were performed in 171 cases with drug-induced allergic liver injury (druggroup) and results were compared with those in 50 cases with acute viral hepatitis type B (virus group).
There was no difference in sex of both groups. A peak was shown in the third decade of age in drug group, while in the second decade in virus group.
There was no difference in latent period. Fever and eruption were initial complaints in drug group, and jaundice and gastrointestinal symptoms were common in virus group. Leucocytosis and eosinophilia were apparently observed in drug group. Significant elevation of serum alkaline phosphatase levels revealed in drug group, while values of serum aminotransferase, serum lactic dehydrogenase, and thymol turbidity test were significantly higher in virus group.
The recovery period of drug group were shorter than that of virus group.

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The lymphocyte stimulation test (LST) to halothane was performed in patients who showed hepatic injury after the halothane anesthesia. Thirty three in 162 cases revealed over 200% of the transformation index. There was no case showed the positive LST in three control groups-healthy volunteers, patients with other hepatic diseases and patients without hepatic injury after the halothane anesthesia. Halothane concentrations added in culture medium were ranged from 0.01μg/ml to 10μg/ml in lymphocytes cultures showed the positive LST, and positive results were chiefly taken under 1.0μg/ml of halothane concentrations. The LST was performed from 2 to 147 (48.8±42.5, mean±SD) days after the onset of hepatic injury in positive cases. The LST positive cases were comprised of 6 multiple exposure cases, including 4 fatal cases, and 27 single exposure cases. All fatal cases were post-menopausal women and died of the massive or submassive hepatic necrosis. Clinical signs and symptoms were generally similar as those of other drug-induced allergic hepatic injury. It is concluded that the LST to halothane is useful and reliable to diagnose the halothane-induced hepatic injury.

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Three hundred and fifty liver biopsy specimens obtained at the Dept. of Gastroenterology, KANTO TEISHIN HOSPITAL for 3 years, between 1975 and 1978, were morphologically reexamined without access to clinical data. Forty three patients with chronic alcoholic liver injury were selected. With reference to clinical records, all of these patients consumed large amounts (over 3 go calculated in terms of Japanese Sake per day for over 10 years) of alcoholic beverages. In this paper, mainly morphological features of the selected cases, which provisionally named "chronic alcoholic hepatitis", were described in detail.
Diagnostic criteria for "chronic alcoholic hepatitis" are shown in Table 2.
Then clinical and laboratory findings are referred and comparison of our cases with those of "alcoholic hepatitis" in the U.S.A. and Europe was done.

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The binding patterns of ICG with plasma proteins in vivo were studied in a case of constitutional excretory defect of ICG and 61 cases of various diseases. Plasma was obtained from the cubital vein after an administration of a large dose (5mg per kg body weight) of ICG. Lipoproteins were fractionated by polyanion-percipitation method, and ICG concentration of each fraction was determined. In vivo, 71% of ICG binded with lipoproteins in which 33% binded with HDL, and 38% binded with LDL. Distribution ratio of ICG in LDL fraction in vivo was significantly lower than that of in vitro loading. In a case of constitutional excretory defect of ICG, binding ratio with lipoproteins in vivo was completely different from that of in vitro loading, suggesting that modification of binding pattern of ICG with lipoproteins in vivo is abnormally strong in constitutional excretory defect of ICG. Plasma disappearance rates of LDL-, HDL-, and non lipoprotein-binding ICG were not significantly different from that of total plasma, suggesting that the binding patterns of ICG with plasma proteins may not be responsible for the abnormal excretory function of ICG. In chronic liver disease, distribution ratios of ICG in HDL fraction were increased, reflecting some but unknown qualitative changes in plasmas lipoproteins.

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ICG Rmax and various liver function tests were measured in 182 patients, including 55 with liver cirrhosis, 66 with chronic hepatitis, 14 with primary hepatoma, 31 with alcoholic liver injury and 16 with fatty liver. ICG Rmax revealed a close correlation with BSP and liver function tests which reflect the degree of protein synthesis in the liver. ICG Rmax and BSP showed similar changes in chronic liver diseases, however, ICG Rmax was more sensitive to evaluate the precise pathophysiological status and the prognosis in liver cirrhosis than BSP.
Liver function tests which reflect protein synthesis in the liver showed high incidences of abnormal values only in liver cirrhosis and primary hepatoma, and incidences of abnormality in the other chronic liver diseases were significantly lower than that of ICG Rmax. Distinct discrepancies between ICG Rmax and those tests were found, suggesting that these tests reflected one aspect of hepatic pathophysiology which could not be evaluated by ICG Rmax.
These results suggested that ICG Rmax reflected most sensitively the changes in the total functioning cell mass, and that more precise pathophysiological status in liver diseases could be evaluated by the combination with ICG Rmax and liver function tests reflecting hepatic protein systhesis.

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On the basis of experience thus far, it is said that the diagnosis of fatty liver is comparatively difficult. It has been reported that the diagnosis of fatty liver can be done by its decreased attenuation number on CT scan among diffuse liver diseases. We investigated 80 cases of which attenuation number revealed below 35Hn (Hounsfield units).
Analysis of correlations between eight variables (T. Cholesterol, β-lipoprotein, Triglyceride, HDL Cholesterol, Cholinesterase, Obesity index, BSP and the degree of fatty infiltration of the liver specimen) and mean attenuation number of the liver were investigated and highly significant correlation was found only between the degree of fatty infiltration of the liver and the mean attenuation number of the liver (r=-0.746, p<0.01).
Therefore, it is concluded that CT scan is an epochmaking morphological examination of fatty liver.

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Glucoregulatory mechanism before, one and three weeks after major hepatic resection was investigated by applying four dimensional autoregressive analysis to the time series of blood sugar (B.S.), insulin (IRI) and glucagon (IRG) during random impulse like glucose injection into femoral vein of mongrel dogs.
One week after the hepatectomy, the impulse response of blood sugar due to the glucose injection resulted an increase in the control area and prolongation of the settling time, whereas those of insulin and glucagon were depressed and augmented respectively.
Impulse responses due to both of the insulin and glucagon were also prolonged in their settling times.
Three weeks after the hepatectomy, the above impulse responses displayed relatively similar time patterns to those of preoperative control ones, which suggested recovery of glucoregulatory mechanism.

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Single and simultaneous localization of α-fetoprotein (AFP) and albumin (ALB) of featal, neonatal rat liver and liver from a rat fed 3'-Methyl-4-Diaminoazobenzene (3'-Me-DAB) diet was studied using peroxidase-labelld antibody method.
1) Early stage of 3'-Me-DAB hepatocarcinogenesis: In verly early stage, when maturation from oval cells to transitional cells began to occure, only AFP was localized in scant cytoplasm of trasitional cells. In a more advaced stage, when maturation from ovall cells to transitional cells and small hepatocytes highly occured, simultaneous localization of AFP and ALB was observed in those cells. When small hepatocytes took appearance as apparent hepatocytes, only ALB was localized in them.
2) Fetal and postnatal rat liver: On Day 12 of gestatin, AFP and ALB alredy localized in all hepatocytes. This tendency continued during the entire fetal life. After birth, AFP containing cells gradually diminished from the periphery of hepatic lobule toward the central area. Finally, all hepatocytes singly contained ALB.
3) The fluctuation of AFP and/or ALB containing cells in the early stage of 3'-Me-DAB hepatocarcinogenesis was very similar to that of ontogenesis of rat liver. That is, the former re-traced the process of ontogenic differentiation of the liver.

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Frequency and degree of occurrence of 8 cytoplasmic expressions were examined in carcinoma cells of minute and huge hepatocellular carcinoma (HCC). Fat accumulation, orcein positive, but neither HBsAg nor copper containing granules, iron stain-positive granules and Mallory's hyalines were seen more frequently in minute HCC than in huge HCC (p<0.001), indicating that the expressions-positive cells appear in early stage of HCC and may be mostly replaced by the negative cells in huge HCC. Bile plug and globular hyalines, however, were frequently seen in minute as well as in huge HCC (p>0.3), indicating that they are rather persistent cytoplasmic expression of HCC throughout the entire course. Clear cell transfor mation and ground-glass change of carcinoma cells were rarely seen with no difference in frequency between both HCC.

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Factors with prognostic significance in the pateints with hepatocellular carcinoma were chosen from 9 clinical signs and 10 laboratory findings. For this analysis, 60 patients who did not received any chemotherapy of longer than 1 month were divided into two groups according to the presence or absence of clinical signs and a life table analysis of survival of the study population were done. Ten laboratory tests were analysed with the respect to patients survival.
It was found that the presence of serum bilirubin concentration of greater than 2 mg/100ml, GOT level over than 150 u, and γ-GTP level over than 100 u were worse prognostic features. Patients with decreased number of peripheral blood lymphocyte and patients with more than 50% of the liver involved cancer as estimated from scintiscan seem to be poor prognostic. Those five factors appear to be useful as objective criteria to establish a clinical stage of patients with hepatocellular carcinoma.

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Activation of furanidyl-5-fluorouracil (FT207) and the effects of Coenzyme Q₁₀ (CoQ₁₀) on the metabolism of FT207 were studied in hepatocellular carcinoma bearing patients.
Administration of CoQ₁₀ elevated serum concentration of 5-fluorouracil (5-FU) to be an active compound of FT207. Therefore, it seemed that co-administration of CoQ₁₀ with FT207 enhanced the metabolism and probably also the anticancer effects of FT207.
Although both CoQ₁₀ and phenobarbital (Pb) are known to induce drug-metabolizing enzymes in hepatic microsomes, however, CoQ₁₀ also inhibits lipid peroxidation as well as EDTA-Na, glutathione, vitamin C, E, and K, whereas Pb promotes it.
So, it may be concluded that CoQ₁₀ has a great advantage of both enhancing main effects and reducing side effects of FT207.

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A case of indocyanine green (ICG) discharge abnormality accompanying a direct-type bilirubin (d-bil)-dominant high bilirubinemia, 28-year old male, is reported hereunder. He was hospitalized for jaundice as the main complaint, but his liver function tests revealed no abnormal transaminase, ALP, γ-GTP except that his d-bil was high. However, his ICG discharge test revealed very low plasma disappearance and transfer rate constants while the BSP's same rates were normal. There were no abnormal findings by laparoscopy and biopsy of the liver tissue under light microscope, but by electron microscope, precipitation of lipofuscin like granules within the hepatic cells or Kupffer cells, enlargement of smooth-faced follicles and swelling of mitochondria were seen.
A case like this with no abnormal findings of liver function tests and morphological studies but having ICG-discharge abnormality with high value of direct-type bilirubin is considered to be the very first case ever reported.

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This case is 21 years-old male complaining of hepatomegaly, which had already been noted at 13 years-old. Several examinations were made on admission at 17 years-old. Scanty hair in axillar and pubic region was noticed. ALP, LAP, γ-GTP, GOT and GPT were mildly elevated. Serum testosterone was reduced and testosterone and 17KS were excreted into urine in small guantities. Three round tumors were demonstrated by hepatic scintigraphy and celiac angiography. Biopsies from tumors under laparoscopy yielded histological findings of focal nodular hyperplasia. During three years and a half after this definite diagnosis, hepatomegaly and abnormal liver function tests have not developed, and no subjective symtoms have appeared. Two of three tumors were able to be demonstrated by both computed tomography and echography which were made recently.
As an association of oral contraceptives with benign hepatic tumors has been described in an increasing number of reports, abnormal gonadal hormone balance may be possible to play an etiologic role in the production of benign hepatic tumors. So, this patient is considered to be very suggestive in this viewpoint.

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