Seventy-two chronic hepatitis patients with repeated liver biopsies were studied. In CPH type B, 7 (50%) progressed to CAH, while none of 9 non-B patients progressed. In CAH, 50% of type B and 40% of non-B patients progressed to cirrhosis, but mean periods required for the progression were 44 months and 75 months, and significantly different (p<0.05). In follow-up of 104 cirrhotics, HCC developed in 3 (20%) of type B, 7 (10-9%) of non-B, and 2 (8%) of alcoholic, but the required periods were more or less the same. Non-B chronic hepatitis seems to require longer periods for progression to cirrhosis. than type B, but the difference seems to become smaller with progression of the disease.

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Interferons (IFNs) were administered to 19 patients with type B chronic hepatitis and one with non-A non-B chronic hepatitis. The activities of peripheral lymphocytic 2', 5'-oligoadenylate synthetase (2-5AS) were determined by Sokawa's procedure and its clinical significance was examined. The 2-5AS activities of type B and non-A non-B chronic hepatitis with free from therapy as well as asymptomatic HBV carriers were significantly low (p<0.001, p<0.05 and, p<0.01) than those of healthy controls. This fact suggested that IFN production system was decreased in chronic viral infection. After administration of IFN to the patients with HBeAg positive chronic hepatitis, disappearance of HBeAg and/or seroconversion to anti-HBe were found in 8 of 19 cases (42%). In this successful group, it was found that 2-5AS activities before the IFN treatment were significantly low (p<0.05), and the ratio of 2-5AS activities of 7 days after IFN treatment to pretreatment activities was significantly high (p<0.01). The better induction of 2-5AS, the more improvement of transaminases and anti-viral effect was also recognized when IFN-β was administered to a patient with non-A non-B chronic hepatitis.

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Three hundred and fifty-three patients with chronic hepatitis diagnosed by peritoneoscopy and liver biopsy were followed for long term and evaluated the survival rates, incidence of hepatocellular carcinoma and it's related parameters. 1) Five and 10 year survival rates were demonstrated on each histologic and peritoneoscopic code number classification. 2) Female's survival rates were higher than males' except CIH and 100+200' code number. 3) Survival rates of HBsAg positive group were slightly lower than that of HBsAg negative group as studied on 400' code number males. 4) HCC and hepatic death were more common in older patients. 5) No significant differences in survival and incidence of HCC were found between drinkers and nondrinkers.6) Serum γ-globulin and albumin level, GOT/GPT ratio and ZTT were not in any tendency, whereas serum AFP level generally showed over20ng/ml in HBsAg positive group.

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The aim of the present study is to clarify the relationship between perivenular fibrosis or intrahepatic fibrosis and ultrastructural changes in the myofibroblast (MFB) or fat-storing cell (FSC) in the fatty liver of obese patients using electron microscope.
For the morphometric analysis of MFB or FSC, a significantly negative correlation was found between the area of fat droplets in MFB or FSC and the degree of collagen deposition around MFB or FSC. Moreover, a significantly positive correlation was found between the area of rER in FSC and the degree of collagen deposition around FSC. In addition, pinocytotic vesicle, dense body, indented nucleus, and microfilament in MFB and FSC were remarkable with the increase of the collagen deposition around MFB and FSC.
The development of the fibrosis around the terminal hepatic venule or in the intralobular space was accompanied by the morphological transformation of MFB or FSC in fatty liver of obese patients.
Namely, the cytoplasm of MFB and FSC shows similar morphological changes with the increase of the collagen deposition around MFB and FSC.
Consequently, MFB and FSC may belong to the same certain cell family which produces collagen fibers.

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Serum level of laminin P₁, a pepsin-resistant fragment of laminin, was measured by a specific radio-immunoassay in 276 healthy subjects and in 51 patients with histologically proven chronic viral liver diseases. The level of laminin P₁ was significantly higher in the infants aged from 0- to 4-year- old than those in subjects aged from 20- 50-year-old.
Comparison of serum level of laminin P₁ with the degree of hepatic fibrosis revealed that the concentration of laminin P₁ generally increased in parallel with the progress of hepatic fibrosis. The positive occurrence of the patients with a serum laminin P₁ level over 2.0E/ml was significantly greater in liver cirrhosis (82%) than that of in chronic acitve hepatitis (29%) (p<0.01). These findings suggest that the measurement of serum laminin P₁ may be an useful tool for the diagnosis of liver cirrhosis.

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Liver and spleen volume were measured by computed tomography in 8 healthy volunteers and in 19 patients with alcoholic liver fibrosis. Patients with alcoholic liver fibrosis were divided into three groups (8 of Grade 1, 5 of Grade 2, and 6 of Grade 3) according to the severity of fibrosis. Each volume was calculated by adding together the area measurements obtained from successive transverse abdominal scans. In the liver volume (mean±SD), alcoholic liver fibrosis Grade 2(1, 284±153³) is significantly larger than the healthy volunteer (1, 027±79³, p<0.01)or Grade 1(1, 096±187³, p<0.01), and Grade 3(1, 481±165³)is significantly larger than Grade 1(p<0.01). The mean volume of hepatocytes was significantly larger in Group 3 than in Group 2 or 1. In the spleen volume, Grade 2 (59±6³)was significantly(p<0.01) smaller than the healthy volunteer(84±13³) or Grade 1 (84±40³), and Grade 3(147±36³)is significantly(p<0.01)larger than Grade 1. In the alcoholic liver fibrosis, liver volume is increasing as the Grade of fibrosis advances.

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For the quantitative assessment of the glucose intolerance in cirrhosis by intravenous glucose tolerance test (IVGTT) and insulin tolerance test (ITT), two steps of experiments with thioacetamideinduced cirrhotic rats were done under automatic glucose monitor. The first experiment which was concerned with analysis of blood sugar curve obtained by IVGTT and ITT revealed the possibility that glucose disposal rate might be prospected by the analytic index of IVGTT and ITT. The second experiment in which glucose disposal rate was measured by hyperglycemic glucose clamp method demonstrated that the prospected values approximated to the measured values. Therefore we concluded that IVGTT and ITT were useful for the prospection of glucose disposal rate without insulin and maximum disposal rate under insulin infusion. In addition, glucose intolerance in thioacetamide-induced cirrhotic rats was thought to be caused by the decrease of insulin secretion and by insulin resistance.

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Sixty one autopsy cases of alcoholic liver cirrhosis (Al-LC)were submitted for clinico-pathological study in order to clarify some pathogenetic factors of Al-LC and hepatocellular carcinoma (HCC). Al-LC and related disorders were classified into following 5 stages. Stage O: alcoholic fibrosis with focal cirrhotic change. Stage l: early stage of alcoholic cirrhosis. Stage 2: fully developed Al-LC, diffuse micronodular thin-stromal pseudolobule formation. Stage 3: Al-LC with partial postnecrotic feature. Stage 4: Al-LC with macronodular pseudolobule formation. The stage of Al-LC progressed in pararell to the increased quantity and duration of alcohol intake. Association of HCC in Al-LC was encountered in 12 cases (19.7%), all of which had strong drinking habit Over 20 years. HCC associated with Al-LC were disclosed not only in cases with stage 4 (22.2%) but also in cases with micronodular pseudolobule (13.6%in stage 2, 31.3%in stage 3). There was no significant correlation between abstinence nor Mallory body formation and development of HCC. These data indicated that even in early stage of Al-LC, careful clinical observation is necessary for the early detection of HCC-Heavy drinking over 20 years is seemed to be important etiologic factor for the hepatocarcinogenesis in cases with Al-LC.

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Des-γ-carmxyprorombin (an abnormal prothrombin, PIVKA-II) was detected in 43 of 83 patients (52%) with hepatocellular carcinoma (HCC) and its concentrations were high in about three fourths of these PIVKA-II-positive patients. In only 4 percent of patients with chronic hepatitis and liver cirrhosis, PIVKA-II was found and its concentrations were low. PIVKA-II was not detected in patients with cancers other than liver cancers and normal subjects. There was no correlation between AFP and concentrations of PIVKA-II. Concentrations of PIVKA-II changed closely in parallel with development of HCC and its treatments, surgical resection of tumors and L-TAI. Detection of PIVKA-II will be valuable in the diagnosis and follow-up of HCC.

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Clinicopathological studies were underwent on hepatocellular carcinoma (HCC) with tumor emboli in the pulmonary artery (PA). 106 autopsy cases of HCC were classified into three groups. Group A: 14 cases with macro-and microscopical tumor emboli in the PA. Group B: 32 cases with microscopical tumor emboli. Group C: 60 cases without macro-and microscopical tumor emboli. 1) Incidence of tumor emboli in the PA was 46 out of 106 cases (43.4%). 2) Main symptoms were dyspnea, cough and chest pain. Especially dyspnea was the most important sign. 3) Maximum diameter of the right descending PA on chest X-ray was the greatest in group A (18.4±2.6mm). 4) Arterial PO₂ showed the lowest value in group A (63.8±13.4 mmHg). 5) ^99mTc-MAA perrusion image was the most useful examination for clinical diagnosis. 6) Few cases died of tumor emboli in the PA in group A and B. 7) Tumor emboli in the PA was frequently encountered in cases with infiltrative type of HCC associated with tumor emboli in the hepatic vein, inferior vena cava or right atrium of the heart.

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The perfusion apparatus has newly been modeled for the isolated rat liver according to the Dr. N.F. LaRusso's model (G-I unit, Mayo Clinic, Rochester, Minnesota), and this experiment was designed to know the changes of the rat liver by the perfusion using the apparatus.
The DNA content and the number of hepatocytic nuclei were morphometrically studied at one, two and three hours of perfusion in the isolated rat livers. The histological changes by the perfusion were also investigated. In addition, oxygen consumption in the liver, GPT activity in perfusate and bile flow were evaluated as the physiological and biochemical parameters of the function of the isolated liver.
Oxygen consumption and bile flow decreased, and GPT activity in perfusate increased more than 2 hours after perfusion. Vacuolar degeneration in hepatocytes around the central vein was microscopically observed 2 hours after perfusion. Necrosis, degeneration and disappearance of hepatocytes were seen in the central zone of the lobules 3 hours after perfusion. They occasionally expanded to the middle zone. The ratio of the DNA content of hepatocytic nuclei around the central vein to that around the portal tract revealed no significant change up to 2 hours after perfusion, but was significantly decreased at 3 hours of perfusion. The number of hepatocytic nuclei around the portal tract was not decreased throughout the experiment, but that around the central vein revealed a significant decrease 3 hours after perfusion.
From these findings, the limit of the experiments using this isolated rat liver perfusion apparatus is concluded to be 2 hours.

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The different choleretic behavior of ursodeoxycholic acid (UDC) from other bile acids was studied using isolated rat liver perfusion. The addition of UDC produced different results from the addition of tauroursodeoxycholic acid (TUDC), cholic acid (CA), or taurocholic acid (TCA) in that it led to striking choleresis accompanied by an increase in the biliary bicarbonate concentraiton. Furthermore, whereas aclearly linear relationship existed between bile flow and bile acid output during TUDC, CA, or TCA administration, the correlation between those two parameters was weak (r=0.64) following addmin-istration of UDC; in fact, the correlation between bile flow and bile acid concentration in the liver as stronger (r=0.67). When UDC+Ouabain was added to the perfusate, the excretion of UDC in bile was accelerated, and as a result the concentration of bile acids in the liver was reduced. This led to suppression of the marked increases in bile flow and biliary bicarbonate concentration. Thus, it appears that UDC accumulation in the liver stimulated the excretion of bicarbonate ions into the bile canaliculi and thereby accelerated choleresis.

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The cholestatic factor (CF) in liver biopsy specimens from patients with variolLs liver diseases was investigated immunohistochemically. Monoclonal antibody to CF from lymphonode cells of the tuberculin-sensitized guinea pigS was used in this immunohistochemical study.
Intrahepatic CF was detected in 11 of 31 patients who were 5 of drug induced liver inj ury, 2 of acute viral hepatitis, 3 of alcoholic liver injury and 1 of autoimmune hepatitis. In all these diseases CF was diffusely and granularly localized in the cytoplasm of many hepatocytes. All CF-positive patients had jaundice in their courses. But, CF was neither present in the liver specimens of patients with symptomatic primary biliary cirrhosis nor extrahepatic obstruction.
These findings strongly suggest that CF correlates with intrahepatic cholestasis in drug induced liver injury, acute viral hepatitis, alcoholic liver injury and autoimmune hepatitis.

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Although bleeeding from gastric varices is said to be less frequent than that from esophageal varices, its hemodynamics have not been clarified yet. The purpose of this article was to analyze hemodynamics of gastric varices by means of percutaneous transhepatic portography which was carried out in 230 patients with gastroesophageal varices.
The incidence of gastric varices was endoscopically 57% of the 230 patients. In patients with remarkable gastric varices, the main variceal supply was the posterior gastric or short gastric vein, while the left gastric vein in those with esophageal varices. Compared to patients with esophageal varices, those with remarkable gastric varices more frequently had a gastro-renal shunt and portal systemic encephalopathy, and showed a lower portal venous pressure.
Thus, there are significant differences of hemodynamics and clinical features between gastric and esophageal varices.

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A 45-year-old man was suffered from diarrhea and abdominal pain 7 hours after consuming approximately 70 g of Amanita virosa, "field mushrooms".
His consciuousness was clear when he was referred to our hospital 5 day after the onset of the symptoms, but his liver function tests revealed severe liver damage.
On the 9th hospital day conscious level fell down and he was diagnosed as having fulminant hepatitis due to Amanita toxin poisoning.
Vigorous treatment, including plasma exchange, direct hemoperfusion, corticosteroid, fructosemanitol solusion, and special amino acid solusion was successful in reversing the comatose state and liver function to normal level.
In Japan Amanita toxin poisoning is very rare and this paper is the first case report of fulminant hepatitis due to Amanita poisoning.

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A 20-year-old woman was admitted due to anorexia, general malaise and fever. She was treated with vasopressin for diabetes insipidus at the age of eighteen. On admission, physical examination revealed generalized icterus and hepatomegaly. Laboratory data showed anemia and increased hepatobiliary enzymes. At laparoscopy, diffuse granulomatous lesions of the liver were noted. Histologically, infiltration of the histiocytic cells was found at the portal area. Immunohistochemically, these cells were negative for lysozyme stain, but were positive for S100 protein stain. An electron microscopic examination revealed the presence of Birbeck granule in histiocytic cells. On the basis of these findings, Histiocytosis X was diagnosed. After administration of vinblastine, diabetes insipidus, jaundice and liver function were improved.

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