In order to clear the acute exacerbation of asymptomatic HBV carrier (AE), clinicopathological investigations were carried out in 183 patients; 34 AE, 119 AVH (type A 30; type B 34; type NANB 55) and 30 chronic hepatitis type B (active 25; inactive 5). Incidences of several symptoms, mean peakvalues of T·Bil, GOT and GPT were lower in AE than AVH. And mean peak values of TTT and ZTT were higher than AVH type B and NANB. IgM class anti-HBc (EIA) was examined in 21 AE and 19 AVH type B, 2 patients (9.5%) were positive in the former but all patients were in latter. Histologically, AE was characterized by slight portal fibrosis, portal and periportal inflammation in addition to the parenchymal damage resembling AVH but less conspicuous Kupffer cell mobilization. Histochemically, the localization of HBsAg was examined in 26 cases of 31 AE and pattern of HBsAg expression was cytoplasmic type or mixed membranous/cytoplasmic type. Intrahepatic HBcAg was also examined in 22 cases and pattern was eytoplasmic type or mixed nuclear/cytoplasmic type. Moreover, follow-up study of 25 AE indicated that the patiients with marked parenchymal changes and cytoplasmic type HBcAg were prone to show seroconversion from HBeAg to anti-HBe in a short time.

View full abstract

Immunohistochemical study of HBsAg and HBcAg in 247 liver biopsy specimens of type B liver diseases was carried out to clarify the (immune) mechanism of hepatocyte lysis particularly in connection with infiltrating inflammatory cells, by double immunostaining using β-galactosidase and peroxidase antibody techniques. HBsAg expressed on the liver cell membrane was frequently displayed in NSRH (27.9%), and also frequent in CAH (14.3%), mainly in the periportal areas. HBcAg was mainly found in the nucleus in NSRH, whereas it was predominated in the cytoplasm of hepatocyte in CAH. Hepatocyte cytoplasm containing both HBsAg and HBcAg were preferentially demonstrated in the severe inflammatory lesions by a double immunostaining. These findings suggest that the increased replicatiou of HBV and its related antigens induces the response of lymphocytemediated liver cell injury in type B hepatitis.

View full abstract

Present study was aimed to clarify the relationship among serum type III procollagen N-peptide (P-III-P) levels, histological findings and immunolocalization of type III collagen of the liver in patients with acute viral hepatitis (AVH). Serum P-III-P levels in patients with AVH were significantly elevated (24.2±8.5ng/m), compared with those in cantrols (7.8±3.0ng/ml). Also, there was significantly positive correlation between serum P-III-P levels and histological findings such as focal necrosis (p<0.02) and cell infiltration (p<0.02). Light microscopic observation using immunoperoxidase method with anti-type III collagen showed that immunoreactive products of type III collagen were clearly seen at the area of focal necrosis, cell infiltration and fiber deposition of the liver in AVH. Electron microscopy showed that many transitional Ito cells were found around the area of focal necrosis and fiber deposition, and numerous fibrils of 20 to 40 nm in diameter were observed around the Ito cell and hepatocytes. Immunoelectron microscopy showed that immunoreactive product of type III collagen was observed in the cisternae the rough endoplasmic reticulum of Ito cells and hepatocytes around the area of focal necrosis and fiber deposition. Consequently, these results suggest that type III collagen is synthesized in the liver and plays an important role for the protection of hepatocytes and the restoration of liver tissue in AVH.

View full abstract

An immunohistochemical examination of keratin, using a polyclonal antibody and four monoclonal antibodies (KL-1, PKK-1, 2, 3), was performed on livers in normal control, acute hepatitis, chronic inactive hepatitis, chronic active hepatitis and liver cirrhosis. In cirrhotic liver, the number of hepatocytes with keratin positivity and with diffuse positivity throughout entire cytoplasm (Diffuse Type) was larger than normal liver. Such hepatocytes were mainly present in the peripheral zones of both hepatic lobules and regenerative nodules, or in and araund the fibrosis localized in a large area. In regenerative micronodules, the number of them was greatest. Diffuse Type was frequently seen in degenerative and pseudoacinar hepatocytes. These results showed that degeneration and regeneration lead to an increase in the amount of keratin and to distribution of keratin throughout entire cytoplasm in hepatocytes. Furthermore, they showed that amount and distribution of keratin in many hepatocytes in regenerative nodules differ from normal hepatocytes.

View full abstract

Acute hepatic failure was induced by an i.v. injection of heat-killed Propionibacterium acnes into BALB/c mice followed by an i.v. injection of a minute amount of lipopolysaccharide (LPS). Most of the mice died of massive hepatic necrosis within 24 hours of i.v. LPS injection. However, an i.p. administration of an immunostimulant, OK432, one hour before LPS injection prevented the mice from death due to hepatic failure and diminished the development of histological changes, especially hepatic necrosis. These results suggest that the generation of OK432 may be involved in the development of acute hepatic failure in the present model.

View full abstract

The role of endotoxin in liver injury induced by D-Galactosamine (GalN) was investigated in rats in vivo, or by using isolated rat hepatocytes (in vitro). In colectomized rats, GalN produced little hepatotoxicity, while it induced severe liver damage by simultaneous administration of lipopolysaccharide (LPS). The liver injury induced by GalN was significantly inhibited by the treatment of nafamostadt mesilate, a complement inhibitor. Although GalN itself produced little hepatocytotoxicity on cultured hepatocytes in vitro, but severe hepatocyte necrosis was induced by GalN and endotoxemia (LPS-treated) rat serum obtained from rats 15 minutes after intravenous administration of LPS. However, LPS itself showed no hepatocytotoxicity in cultured hepatocytes. These results indicate that hepatocyte degeneration induced by GalN itself may be followed severe liver damage due to hepatocytotoxic factors like complement in endotoxemia rat serum.

View full abstract

A long-term clinical study of SF-1008C was perfermed in 96 patients with decompensated liver cirrhosis by periodic evaluation of nutritional status, symptomatic improvement and life prolongation. Definite improvement was seen in the second week of treatment in flapping tremor scores, number connection test times and encephalopathy severity. At 6 weeks, one-half of the patients were discharged, and at 3 months, more than 70% of all the patients improved to outpatient status. The Karnofsky performance scale also showed significant improvement after 2 weeks. In addition, Fischer's ratio (BCAA/AAA) and nutritional indexes showed improvement. Assessment of global improvement, safety and clinical usefulness revealed significant improvement with long-term use of SF-1008C.
The cumulative survival rate in the SF-1008C treated group was significantly greater than that in the historical data group. Therefore, SF-1008C was considered to have high clinical value inprolonging the life of patients with decompensated liver cirrhosis.

View full abstract

A canine model of an acute hepatic failure was created by the administration of DMN (30mg/kg) via portal vein. Using this model, the hepato-pancreatic relationship was studied by measuring the pancreatic endocrine function of portal blood and hepatic blood flow. As a result, while the plasma level of IRI of portal blood was higher than basal level of IRI when the hepatic damage was mild, the former was similar to control when the hepatic damage was severe. On the other hand, the more severe the hepatic damage was, the higher the plasma level of IRG of portal blood was. Hypoglycema and a considerable high level of portal IRG were shown in an acute hepatic failure.
These results strongly suggest that pancreatic endocrine function of portal blood may reflect the grade of hepatic damage and a hormonal or neural hepato-pancreatic relationship may exist between the liver and the pancreas.

View full abstract

We investigated cell kinetics of regenerating liver, useing flow cytometric (FCM) analysis of hepatocytes' and Kupffer cells' (Kc) DNA contents prepared from the same rat liver. Normally continuing until 8 wks, influence of polyploidization on regeneration was excluded through use of ploidy-stable rats. Changes in the cell cycle of hepatocytes in regenerating rat liver (8-12wks) showed the ratio of S phase and G2M phase increasing after 24hrs following hepatectomy, the ratio of binucleate cells decreasing during regeneration, and different courses in each ploidy class (4C, 8C). Regarding Kc, the ratio of S phase and G2M phase increased after 48 hours following hepatectomy.
A convenient method of analysis of change in cell kinetics of hepatocytes and Kc by FCM was thus established.

View full abstract

The nuclear DNA contents of paraffin-embeded specimens of 53 hepatocellular carcinoma cases were measured by means of flow cytometry. DNA indexes were calculated and the correlation of DNA indexes with clinico-pathological findings was studied.
Three years survival rate of aneuploid cases was 43.3%, and significantly lower than 95.2% of the diploid cases (p<0.001).
Serum AFP level of aneuploid cases was 2887.7±1885.4 and was 1065.3±325.0 in diploid cases (p<0.05). DNA ploidy did not closely correlate with histopathological findings.
The DNA indexes of the tumors of the second operation were different from the first ones in 3 cases. They seemed to be new tumor growth rather than recurrence of the primary tumors. The recurrent tumors had the same DNA indexes as those of the primary tumors. From these studies, the flow cytometric analysis using cell suspensions from paraffin-embedded blocks is useful to evaluate the prognosis and the biological characteristics of hepatocellular carcinoma.

View full abstract

Plasma endotoxin and reticuloendothelial (RES) function were examined in fifty cases of hepatocellular carcinoma undergone transcatheter arterial embolization (TAE). Although plasma endotoxin level increased on the next day after TAE in all TAE cases, it recovered on the third day in cases without complication. On the other hand, in cases with complication, plasma endotoxin level remained to be high continuously even three days after TAE. Experimental TAE using rabbits with VX2 tumor showed that increase of plasma endotoxin level and reciprocal decrease of RES function after TAE were noted. In addition, portal endotoxin level after TAE was higher than control without TAE. It was proposed that endotoxemia after TAE was caused by decreased RES function and increased intestinal absorption of endotoxin. Furthermore, disappearance curve of plasma endotoxin after addition of standard endotoxin suggested that endotoxin inactivating activity in the plasma was decreased by TAE.

View full abstract

51 year-old man admitted to our institude becase he had hepatocellular carcinoma of 4.3×4.2cm in size at the anterior segment of the liver and tumor thrombus in the portal vein. After transcatheter arterial embolization (TAE) with spongel, addition to the effect of TAE, the leson of the anterior segment became completely necrotic because the tumor thrombus acted to TPE. This seemed to be a interesting phenomenon which showed complete necrosis of both the carcinoma of inner and outer capsule and tumor thrombus in the portal vein, which did not usually became necrotic by TAE.
The transient of high echo spots which were associated with liver infarct was observed by echography.

View full abstract

A 50-year-old man was hospitalized with the chief complaints of abdominal pain and fever. Results of various kinds of medical imagings led to the diagnosis of hepatocellular carcinoma (HCC) with metastasis to the spleen and tumor thrombi in the portal and splenic veins. An operation was not possible, and we gave one arterial injection of anticancer agents and did transcatheter arterial embolization (TAE) twice, with about one month between one treatment and the next. After each TAE, the tumor grew smaller, and after the second TAE, the splenic vein thrombus was not found. Metastasis to the spleen is rare in HCC and splenic vein thrombi have not been reported before, to our knowledge. That a tumor thrombus was found in the drainage vein of the metastatic lesion as well as that of the main lesion is of importance to a discussion of the mechanism of such thrombi. The effect of TAE treatment suggests that the metastatic lesion in the spleen and the tumor thrombus in the splenic vein were supplied by arterial tumor vessels.

View full abstract

A 48-year-old woman, who had been treated as liver dysfunction for over 2 years, visited Tokyo Musashino Hospital. She was apparently healthy. However, only serum GOT level was abnormally high (203mU/ml), which persisted for the following 9 months. She was admitted to the hospital for further examination in March 1987, with the data of serum GOT level as high as 305mU/ml. Heart and muscle disease was excluded. Liver biopsy specimen revealed no evidence of chronic liver disease. Transaminases levels of hepatic cytosol were normal. The patients'serum showed an atypical GOT migrated to a position of slow-βglobulin by electrophoresis. Then, the atypical GOT was found to be an immunoglobulin (IgGκ)-complexed macromolecule of supernatant GOT. We report a present case with reference of 23 cases reported before. Physicians should be aware of this phenomenon so patients are not subjected to unnecessary examinations or treatments.

View full abstract