Gianotti's disease is a special type of hepatitis B virus (HBV) infection in infancy and childhood. The pathogenesis of skin eruption which is an important sign of this disease has not been well established yet. In order to elucidate the mechanism of skin eruption, we performed immunofluorescent study on biopsied material of skin eruption for the localization of HBsAg, IgG, IgM, and C3. The cases examined included 9 cases of Gianotti's disease and 3 cases of Gianotti's syndrome (negative for HBsAg, as a control).
Histopathologically, skin eruption of Gianotti's disease is closely similar to that of Gianotti's syndrome and is characterized by perivascular lymphocytic and histocytic infiltrations around small vessels in upper dermis, associated with no evidence of necrotizing vasculitis. Immunofluorescent study revealed fine granular and/or linear deposition of HBsAg, IgG, IgM, and C3 along the entire wall of small vessels with perivascular inflammatory infiltrations in upper dermis. Positive deposition of these antigens were observed in 4 cases among 9 cases of Gianotti's disease and no deposition was recognized in any Gianotti's syndrome.
As a result of this study, it was strongly suggested that the transient deposition of antigenexcess HBs antigen-antibody (immune) complex to the wall of small vessels of skin plays an important role on the formation of skin eruption of Gianotti's disease.

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This study aims to evaluate the effects of exogenous human leucocyte interferon on hepatitis B virus in patients with chronic active hepatitis. Human leucocyte interferon (HLIF) was parenterally administered to five young Japanese males who were found to have hepatomegaly, elevated transamine activities, persistently positive HBsAg and HBeAg, and high level of DNA polymerase activity. The initial dose of HLIF was daily 10.0×10₅ IU given intramuscularly for several months, and total dosage of HLIF ranged from 1.5×10⁷ to 9.6×10⁷ IU. Total amounts between 5.0×10⁷ IU and 9.6×10⁷ IU were associated with a rapid fall in DNA polymerase activity and a disappearance of e antigen in all patients. In addition, a longer term and larger amount of HLIF resulted in a marked fall in HBsAg titer in one of four cases and a definite improvement in liver function tests in two of five. However, they began to rise again toward the pretreatment level one month after the withdrawal of treatment. The follow-up liver biopsies performed on two patients who received a relatively larger amount of HLIF revealed a much less inflamatory activity, i.e., transition to chronic persistent hepatitis, indicating a definite morphological alleviation. Serial measurement of endogenous lymphocyte interferon level stimulated by Sendai virus also showed an increase after the treatment in one cases. From these results, we conclude that human leucocyte interferon therapy, if given in a longer term and larger amount, is beneficial on HBsAg positive chronic active hepatitis.

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Of 159 cases with acute viral hepatitis, 15 cases (9.4%) was old aged patients above 60 years old. Two of the cases died in the aged patients, although none of the patients died except the aged group in the studied period. Complications such as diabetes mellitus and bacterial infection were thought to be contributed to the ominious course of the patients with acute hepatitis. Prolonged duration before normalization of the liver function test was seen in the aged patients with acute hepatitis in which cases progression to chronic hepatitis or persistent hepatitis were seen. These result suggests that clinical course and progress of acute viral hepatitis in the old aged patients are significandy different from younger patients.

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In order to clarify the role of genetic factors in the pathogenesis of chronic liver diseases, HBsAg, autoantibodies and Human Leucocyte Antigens (HLA) were investigated in 30 patients with chronic active hepatitis and 20 patients with hepatic cirrhosis. The increased frequency distribution of HLA-B7 was found not only in the patients with chronic HBsAg positive liver diseases but also in the group without autoantibodies.
The genetic study in one family showed that members with liver diseasc had common HLA haplotype.
From these results, it can be presumed that genetic factors play a role in the pathogenesis of chronic liver diseases.

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Ten serum protein subfractions in the courses of hepatic diseases (75 cases in total) were determined to know the diagnostic values of these proteins. Among the proteins made by the liver, prealbumin fell in the active phase of acute hepatitis and normilized promptly by converlescence. In chronic hepatitis prealbumin was moderately decreased, and in cirrhosis it was the lowest. Transferrin decreased only slightly in active phase of acute hepatitis, and markedly in chronic hepatitis and cirrhoSis, β₂-glycoprotein 1 showed the same tendency as prealbumin. α₁-antitripsin and IgA were elevated in all the hepatitis, and did not decrease up to normal range by the normalization of GPT. β₁C-globulin and IgM were high in acute hepatitis, the former being normal in chronic diseases. IgG and IgM were high only in active phase of chronic hepatitis and cirrhosis.

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LPS-stimulated peritoneal exudate cells exhibited a significantly potent anti-tumor activity in mice. A marked inhibition of DNA synthesis in tumor cells was observed when tumor cells were co-incubated with the activated peritoneal exudate cells. The inhibition of DNA synthesis in tumor cells was also shown by incubating tumor cells with the culture supernatant of activated peritoneal exudate cells. Interestingly, a different anti-tumor activity of the activated peritoneal exudate cells was observed by changing the combination of activated cells and target tumor cells in both parameters.
The activated cells from C3H mice wete shown to have the more potent anti-tumor activity to hepatoma cells (MH134) than those from DD mice. Conversely, the activated cells from DD mice were more potent than those from C3H mice in inhibition of DNA synthesis of Ehrlich ascites tumor having singeneic origin of DD mice.

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137 cases with slight elevation of SGOT and SGPT, whoes diagnosis were quite difficult clinically, were studied: 41, chronic inactive hepatitis; 19, chronic active hepatitis; 25, cirrhosis; 25, fatty liver; 10, acute hepatitis; 7, NSRH; 2, fibrosis and 5, normal.
The average age was in fourth decade, younger than that of the cirrhosis by 10 years. No sexual differences were noted in the CIH and normal, whereas 4-7 times higher frequency was observed in male in the others. Posttransfusion non B hepatitis was frequent in the CIH, and hepatitis B was in the CAH. Drinking influenced cirrhosis. SGPT was high in acute hepatitis, ICG and ZTT were abnormal in the CAH and cirrhosis and gamma-globlin was high in cirrhosis: these abnormalities were slight, so unuseful for differential diagnosis. After 6 months SGOT and SGPT became normal in the normal, FL, and NSRH, but still abnormal in the others.

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To elucidate immunological mechanisms in the development of experimental liver cancer, 59 guinea pigs were fed 0.0042% (W/V) diethylnitrosoamine (DEN) in drinking water for 12 months. Liver cancer was induced in all animals during the 4th month. Anti-liver cell membrane antibody (LMA), anti-smooth muscle antibody (SMA), anti-nuclear antibody (ANA) and anti-mitochondrial antibody (AMA) were detected by the indirect immunofluorescent technique, and rheumatoid factor (RF) by the RA test kit as indicators of humoral antibodies. Circulating soluble immune complex-like substances were determined by Clq binding activity (Clq-BA). Peripheral lymphocyte counts and the purified phytohemagglutinin (PHA-P) skin test were performed as indicators of cellular immunity.
The incidence of seropositivity for LMA (P<0.05) and RF (P<0.01) was increased in animals with liver cancer compared with non-cancer bearing animals. The incidence of LMA was higher in early cancer than in late. AMA was observed in the precancerous and early cancerous stages. ANA was not found during the course of the experiment. Clq-BA was elevated in association with seropositivity of LMA (P<0.05) and RF (P<0.02). The absolute and relative peripheral lymphocyte counts were increased after DEN feeding. Reactivity to the PHA-P skin test was decreased only at the 3rd and 4th month, irrespective of the presence of the cancer.
These results suggest that some immune responses occur in early cancer, which are associated with the development of cancer.

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In 54% of patients with hepatocellular carcinoma, disc electrophoresis of sera revealed specific Band II which was the second band from the anode using 10% and 20% double layered polyacrylamide gel. Biochemical characteristics of this enzyme was studied. The Band II detected in the sera of the patients with hepatocellular carcinoma (HCC) and extracts from HCC disappeared after the treatment with neuraminidase. After digestion of materials including normal subjects by bromelain, a single band was observed at the coincided portion of Band II in this electrophoresis. Concanavalin A sepharose chromatography divided the second fraction which was obtained by gel filtration of the extract from HCC using Sephadex G 200 into two fractions, i.e., Con A binding and non-binding fractions, of which the latter showed Band II on polyacrylamide gel electrophoresis but the former did not. The hepatocellular carcinoma specific γ-GTP was separated from non-binding fraction to Con A by chromatography of DEAE-cellurose column with NaCl gradient.
It is not clear whether this HCC specific γ-GTP has properties of carcinoembryonic characteristics, or not.

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HBsAG positive chronic hepatitis fluminated with disseminated intravascular coagulation: Report of an autopsied case.
A 38 year old female was found to have liver dysfunction during an examination for general fatigue and anorexia 4 months before admission. A week before admission, the patient had fever, jaundice and facial edema. A day before admission, jaundice developed, and gastrointestinal bleeding and disturbance of consciousness appeared. On admission, biochemical laboratory data revealed acute hepatic failure associated with disseminated intravascular coagulation. On the 4th hospital day, the patient's condition deteriorated and he died in a state of hepatic failure. Autopsy revealed massive hepatic necrosis with lymphocellular infiltration and fibrosis of portal area. It should be considered that HBsAG positive chronic hepatitis was acivated by disseminated intravascular coagulation.

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The clinical course, diagnosis and therapy of Crigler-Najjar syndrome type-1 (the first case in Japan) was described. Jaundice appeared at 3 days of age and developed progressively to 34.8mg/dl (entirely indirect type). Despite of repeated exchange transfusions, hyperbilirubinemia had persisted. On admission (3 months of age), clinical manifestation was unremarkable except for jaundice. The total bilirubin level in serum was 25.49mg/dl with direct fraction of 0.42mg/dl Liver function tests, hematological tests including hemolysis were within normal limits and histological examination of hepatic architecture was also normal. Bilirubin concentration from duodenal juice was 0.98mg/dl containing a trace amount of bilirubin glucuronide. Since hepatic bilirubin UDP-glucuronyltransferase activity, in vitro, was not detected, and phenobarbital administration had no effect on serum bilirubin levels, a diagnosis of Crigler-Najjar syndrome type-1 was made. The intermittent phototherapy was successfully used to control hyperbilirubinemia. The patient is now 2 years old and has no signs of kernicterus.

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A 57-year-old male diagnosed Dubin-Johnson syndrome complicated by hepatocellular carcinoma was reported. Successful treatment by extensive right hepatic lobectomy provided the opportunity to study the disease process at a time when most parenchymal cells were newly regenerated.
Before the lobectomy, liver surface showed cirrhotic pattern and black spots were observed sporadically at laparoscopy. Dubin-Johnson pigments were scarce microscopically and most parenchymal cells were free of pigment. At this time prolonged bromosulphalein (BSP) test did demonstrate the second rise in plasma BSP level at 180min. The second rise of serum indocyanine green (ICG) level was not observed.
After the lobectomy, prominent enlargement of the left hepatic lobe appeared. Black liver surface was noted on laparoscopy, and a massive amount of fine pigments, 1μ in diameter, were accumulated in almost all the hepatocytes in the course of hepatic regeneration.Electron micrographs showed the fine pigments were consisted of aggregated small electrondense grains and were thought to be on an early stage in the formation process of coarse pigment characteristic to DubinJohnson syndrome.

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An unusual case of liver cirrhosis with transient appearance of IgG-L type M proteinemia was reported. The patient was a 51 year old male, who Was hospitalized because of ascites and hepatic coma. On admission, serum electrophoresis revealed a step-up pattern in the γ-region with elevated IgG (3773mg/dl). The immunoelectrophol etic analysis disclosed monoclonal IgG, type L. The urine was negative for Bence-Jones protein and skeletal X-ray revealed no osteolytic lesions. M proteinemia disappeared one month after admission and transformation to polyclonal gammopathy was observed. The transient appearance of M proteinemia in the course of liver cirrhosis has never been reported in the literature according to our survey.

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37 year-old man in early stage of primary biliary cirrhosis suffering from prolonged jaundice and generalized itching was reported in this paper.
After the treatment of D-Penicillamine, jaundice and liver function tests were markedly improved, and the copper contents in hepatocytes of liver tissue were significantly decreased.
In three months before entry he experienced icterus and itching on the skin. On the day of admission, the liver was palpable 3cm below the right costal margin, total bilirubin was 8.4mg/dl, serum GOT was 45, GPT was 26 and alkaline phosphatase was 15.3 U (K.A.). After entry jaundice and serum alkaline phosphatase and ceruloplasmin levels were increased, and anti-mitochondrial antibody was positive.
Laparotomic investigation disclosed the precirrhotic stage of the liver without the extrahepatic obstruction of bile ducts and liver biopsy specimens showed the early stage of primary biliary cirrhosis with massive deposits of copper granules in most hepatocytes. Electromicroscopical studies revealed proliferation and enlargement of endoplasmic reticulum, dilatation of intracristal space in mitochondria, and dilatation of bile canalicula with amorphous substances and shortening & reduction of microvilli.

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