In order to evaluate the HBeAg/anti-HBe system in HBV infection, we surveyed HBeAg/anti-HBe in sera of patients with HBsAg positive chronic liver diseases (CLD) and asymptomatic HBsAg carriers (AsC) by passive hemagglutination method (HA method) and compared the results with that by immunodiffusion method (ID method).
Out of 166 HBsAg positive sera from patients with CLD, HBeAg was detected in 43 cases (25.6%) by HA method, as compared to 15 cases (9.0%) by ID method. In contrast with the wide difference of the detection rate of HBeAg in CLD between two methods, in 113 of AsC the positive rate increased only slightly as to 26.5% by HA method from 20.4% by ID method. This suggests that the titer of HBeAg in CLD is lower than in AsC. The log2 geometric mean titer of HBeAg in AsC was 6.9±1.4, significantly higher than the valeu of HBeAg in group of persistent hepatitis and chronic hepatitis (5.7±1.7) and group of cirrhosis and hepatoma (4.6±0.9). HBsAg titer was higher in cases with positive HBeAg than in cases positive for anti-HBe.
There was a statistically significant correlation between HBsAg titer and HBeAg titer in AsC group, but in liver diseases the correlation was not clear. Thus the findings in HBeAg/anti-HBe system in HBV infection by HA method confirmed some of the results by ID method and furthermore added some new informations on it.

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The subtype of HBs antigen was compared between children and adult carriers. The children were 68 patients examined in the pediatric clinic of the Gifu Hospital, Prefecture of Gifu, during a period from 1976 to 1978. All of them were positive for HBs antigen. Of them, eight were affected with acute hepatitis. Of the remaining sixty, some were affected with miscellaneous diseases and others found incidentally to be positive for this antigen.
The ratio of subtype adw/adr was 6/2 for the children with acute type B hepatitis, 43/17 for the remaining 60 children, 22/2 for adults affected with acute type B hepatitis (1977-1978), 13/109 for adult blood donors, and 13/45 for adults under health examination "in dock". In short, adw was predominant in the first three groups, and adr in the last two groups. There was a statistically significant difference between adw and adr in every group (p<0.001).
When the ratio of subtype adw/adr was determined in the 60 children, exclusive of those affected with acute hepatitis, it was 2/8 for children whose mothers were HBs antigen carriers and 3/4 for children whose fathers were HBs antigen carriers. It was 31/2 for children whose parents were negative for HBs antigen. There were significant differences between the group of children with carrier mothers and that of children with negative parents (p<0.001) and between the group of children with carrier fathers and that of children with negative parents(p<0.005).
When the subtypes were observed in age groups of the 60 children, exclusive of those affected with acute hepatitis, adw was predominant in three age groups, 0-5, 6-10, and 11-15 years, and adr in groups of 16 years and more of blood donors and those under health examination "in dock" (p<0.02).
When the 60 children were followed up for changes in HBs antigen for more than a year, a very few of them (three of 29 children) turned to be negative for this antigen, and most of them remained positive for the antigen throughout the period of follow-up observation.
The ratio of subtype adw/adr of acute type B hepatitis in the Gifu region was 22/11 over a period from 1973 to 1974 and 22/2 over a peiod from 1977 to 1978. Therefore, adw was predominant over both periods.
As a result, it was concluded that the vertical infection with HB virus had been carried out mainly with adr in the Gifu region and that the horizontal infection was recently performed mostly with adw. It was presumed that children positive for HBs antigen might have been carriers of subtype adw.

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An unique component polypeptide (MW 49000 dalton) bearing all of the known antigenic determinants (a, Re, d, and r) was isolated by treatment with sodium dodecyl sulfate, gel filtration, and SDS polyacrylamide gel electrophoresis of purified 22-nm particles from HBV (adr) infected human plasma pool. This polypeptide, designated as p-49, splitted into two smaller polypeptides of different molecular weight-22000 (p-22) and 27000 dalton (p-27)by reduction with 2-mercaptoethanol. p-27 and p-49 were glycoproteins. The antigenicity assayed by reversed passive haemagglutination or haemagglutination inhibition and the immunogenicity tested by injection to mice of p-49 were almost same as 22-nm particles, although significantly superior to the two major component polypeptides-p-22 and p-27.

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1) A substance reacting with SDS-treated small spherical forms of HBsAg was found frequently in HBeAg positive sera of persistent antigenemia. (2) This substance reacted with anti-HBs antibody as well. 3) The density of this substance was estimated as 1.21 by equillibrium buoyant centrifugation. 4) The sedimentation rate of the substance fell between those of Dane particles and small spherical forms of HBsAg, and was identical to that of tubular forms. 5) The reactivity of the substance disappeared by digestion with pronase.
These data imply the existence of a specific protein on the tubular forms in the sera positive for HBeAg, reacting with the inner structure of the HBsAg.

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The cell membrane of T lymphocytes has been stained clearly by immunoperoxidase method with anti-human thymocyte serum on formalin fixed and paraffin section of liver biopsy specimens.
By this method, T lymphocytes were examined in thirty one cases which were divided into the following groups; 3 with acute hepatitis, 20 with chronic hepatitis, 6 with liver cirrhosis and 2 with other liver diseases.
T lymphccytes were predominant both in portal tracts and in acinus compared with non-T lymphocytes.
T lymphocytes, especially in chronic liver diseases, were often contact with and/or surrounded degenerated hepatocytes at piecemeal necrosis and also in acinus. These findings were considered fundamental to elucidate the mechanism of the hepatocellular necrosis.
Our results support histrogically the view that T lymphocytes play an important part in the pathogenesis of the liver cell necrosis.

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When the peripheral blood lymphocytes from patients with various types of hepatitis were stimulated in vitro with liver specific protein, lymphocyte transformation and MIF production were detectable in many cases, especially in chronic active hepatitis. MAF-containing culture supernatants of these lymphocyte activated guinea pig macrophages inhibited the albumin biosynthesis of the isolated liver cells. These results suggest a possibility that the soluble substances released from activated macrophages are involved in the immunological pathogenesis of chronic active hepatitis in addition to the involvement of antibody-dependent cell-mediated cytotoxicity.

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Serum mitochondrial GOT (GOT_M) and ornithine carbamyl transferase (OCT) activities were examined in 150 cases of hepatobiliary diseases. The serum level of GOT_M and OCT in normal controls was 3.4±1.2 and 2.6±0.9 units, respectively. Both activities were elevated in acute hepatitis, chronic active hepatitis, liver cancer and obstructive jaundice and GOT_M was more than 10 units and OCT was more than 20 units in these diseases. The ratio of GOT_M to total GOT activity was 25.1% in normal controls, while it remained as low as 12-16% in the active stage of hepatobiliary diseases. The ratio was elevated up to 25-30% in acute alcoholic hepatitis or acute biliary obstruction, Serum OCT level was also markedly elevated in these diseases. The disappearance rates of GOT_M and OCT in acute hepatic disorders were so rapid and the apparent half-life of GOTM was 0.6 days, while that of OCT was 1.0 day in acute viral hepatitis. In alcoholic hepatitis, the apparent half-life of GOT_M was 1.3 days and that of OCT being 1.8 days. The analysis of the disappearance rates of GOT_M and OCT seems to give useful informations to evaluate acute hepatic disorders.

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The feasibility and safety of selective hepatic venography using a three-lumen, twoballoon catheter were studied. The catheter was originally developed for selective venography, blood sampling and organ irrigation. The shaft part of catheter is made of silicon rubber and the balloon part is made of latex rubber. 30 mongrel dogs with their body weights ranging from 15 to 20Kg were used in the present experiments. The catheter was introduced through the right femoral vein and advance into the inferior vena cava near the orifice of the hepatic vein so that the proximal and distal balloons were located distally and proximally to the orifice, respectively. Whenever this location of the catheter was accomplished, satisfactory hepatic venograms were obtained by injecting 15 to 20ml of 76% Urografin. A pressure change within the hepatic and portal veins was comparatively monitored by introducing two other catheters, one into the portal vein, the other located between the balloons. The maximal pressure developed during venography did not exceed 25 to 30mmHg for both veins. In addition, the pressure patterns obtained from both veins during venography were almost identical. Thus, it appears that the pressure added between the balloons during the injection escaped, through the hepatic sinusoid, to the portal vein which seems to have enough capacity to buffer the pressure elevation. These experimental findings indicate that the hepatic venography using a three-lumen, two-balloon catheter is a relatively safe and effective diagnostic method.

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Relationships between Hepaplastintest, prothrombin time, albumin, γ-globulin, GPT, and the effective hepatic blood flow of ¹⁹⁸Au-colloids as a measure of effective hepatic blood flow were studied by correlation analysis, in 50 patients with liver diseases, including chronic hepatitis or cirrhosis. Simple correlation coefficients were highly significant between Hepaplastintest, prothrombin time, albumin, and the effective hepatic blood flow; however, not between GPT or γ-globulin and the other parameters. Further correlation analysis revealed a highly significant partial correlation coefficient between Hepaplastintest and albumin and the effective hepatic blood flow; however, not between Hepaplastintest and albumin. As effective hepatic blood flow is considered to be proportional to the liver parenchymal volume, the above results indicate that vitamin-K-dependent clotting factors, as well as albumin, reflect the liver cell mass.

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Changes of hepatic volume and effective blood flow in liver diseases were studied. For a measure of effective hepatic blood flow, a hepatic fractional clearance of 198Au-colloids was determined, which was obtained from the disappearance rate multiplied by the fraction of injected dose taken up by the liver. Hepatic blood flow appears to have a wide normal range and also to be affected by aging. The effective hepatic blood flow was normal or not markedly decreased in patients with acute hepatitis who had progressed favorably. However, in patients with fulminant hepatitis it was decreased severely. In subjects with normal blood flow values, a significant correlation was found between the blood flow and liver volume, suggesting that effective hepatic blood flow is proportional to parenchymal volume in an unanesthetized, resting state. These observations led to evaluating the progress of diffuse liver diseases. Biopsied cases showed good accordance of changes in volume and blood flow with changes indicated by morphological criteria.

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In order to elucidate the morphogenesis of an interruption of the peripheral portal branch which is seen in the cases of idiopathic portal hypertension (IPH), histological observations were carried out on the livers of autopsy cases of schistosomiasis japonica (SJ) and of rabbits with experimental SJ. Vascular changes of the liver in chronic SJ and liver cirrhosis were examined using clear preparations and soft X-ray films.
In general SJ begin with matured egg embolism in the portal vein, followed by numerous thrombophlebitis and peripylephlebitis along the intrahepatic portal vein. With the progress of these lesions, fibrosis spread over the liver. Finally, egg nodules turn to scar and the fibrosis is rapidly improved. The characteristic features of the vascular structural changes in the liver of chronic SJ were the narrowing, crush and the change to shape like a weeping willow of the peripheral branch of the portal vein, appearance of obtuse branching angles, and the reduction of the number of branching. These findings contrast to those in liver cirrhosis.
Histological findings and vascular structures of the liver in IPH and chronic SJ showed close resemblance, and the change of portal vein was also sugested as a possible primary lesion in IPH. However, the splenomegaly which is always seen in IPH was not frequently noted in cases of SJ. It suggests some problems in the morphogenasis of IPH despite of those similar findings in IPH and chronic SJ.

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A pathomorphological study was carried out on 12 cases of hepatocellular carcinoma (HCC) with marked lymphnode metastasis among 154 HCC cases, autopsied at the Department of Pathology, Kurume University School of Medicine from January 1974 to August 1978.
The results obtained were as follows;
1) Metastasis was seen in the peripancreatic, the periportal and the periaortic lymphnode, in ordor of frequency.
2) According to gross classification of HCC (Nakashima & Sakamoto's), infiltrative type of 4 cases, multinodular type of one case and mixed type of 7 cases were seen.
3) Histologically, Edmondson's grade II of 5 cases, grade II-III of 2 cases, grade III of 4 cases and grade IV of one case were seen.
4) Metastatic HCC in the lymphnodes were histological classified into two groups: island cell type and free cell type. Tumor cells of island cell type were cohesive in each other and formed island. Tumor cells of free cell type were non-cohesive and showed loose arrangement.
5) Albumin positive cells were highly seen in metastasized HCC in the lymphnodes (81.8%) using immunoperoxidase (PAP) technique On the other hand, Alphafetoprotein positive cells were seen in only 18.2% of metastasized HCC in the lymphnodes.

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This is a report of an infant, who had a transmission of hepatitis B virus (HBV) from her father. The 44-day-old female infant had a emergency blood transfusion before a cardiac surgery from her father. After the operation, her father turned out to be an asymptomatic HBV carrier without any clinical signs. Subsequently she developed persistent HBs antigememia Her liver-function tests had been entirely unremarkable. The postmortem examination of liver histologically showed no diagnostic changes. Her mother was negative for HBV antigens in blood. Therefore, it was obvious that she became an asymptomatic persistent HBs antigenemia following blood transfusion from her father. Also discussed were pathogenesis of hepatiti sB and applicable mechanism whereby asymptomatic HBV carrier condition could develop.

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Intrahepatic cholestasis and secondary hyperlipidemia developed in a forty-one years old woman. Laboratory data, histology of the bioptic liver specimen and endoscopic retro grade cholangiography were consistent with intrahepatic cholestasis. Jaundice continued for 17 months inspite of steroid therapy. During this treatment, each level of serum lipid fractions increased remarkably, such as cholesterol 3240mg/dl, triglyceride 608mg/dl, phospholipid 206mg/dl, accompaning elevated serum alk. phosphatase (903u), γ-glutamyl transpeptidase (4548u), leucine aminopeptidase (258u) and serum bile acid proportionately. Furthermore, electropholetic pattern of serum lipoprotein showed an abnormal running band of low-density lipoprotein (LDL) which seemed to be influenced by increased lipoprotein-X (Lp-X). Sequential addition of cholestyramin and diet therapy resulted in the improvement of hyperlipidemia.
Although her clinical course and laboratory data indicated to be chronic cholestatic liver disease, this case should be diagnosed of variant acute intrahepatic cholestasis from the histology.

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