Serum HBV-DNA was assayed serially in the early phase of acute hepatitis B virus infection, and its changing patterns were compared between those who became HBsAg carriers and those who cleared HBsAg after acute hepatitis. Maximal values of serum total bilirubin and GPT levels were also compared between the two groups.
Serunm HBV-DNA was detected only immediately before the peak of serum GPT in two cases who cleared HBsAg. In two cases who became HBsAg carriers, serum HBV-DNA was positive before elevation of serum GPT, declined concurrently with the period of serum GPT elevation, and reelevated after acute hepatitis subsided. The transient decline of serum HBV-DNA was considered to be the result of eliminating reaction of the host to the virus.
The peak levels of serum GPT and total bilirubin was obviously lower in the cases who became HBsAg carriers than the cases who cleared HBsAg.

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To evaluate the role of the expression of HBV-associated and HLA class I antigens on liver cell damage, we examined by immunoperoxidase procedure the distribution of HBcAg, HBeAg and HLA class I antigens in cryostat liver sections from 18 chronic carriers of HBsAg using monoclonal antibodies. Of 14 displayed HBeAg expression, 11 coexisted with HBcAg. In these liver tissues, the distribution of HBcAg and HBeAg were concordant. Thus both antigens were mainly observed cytoplasm while they localized in both cytoplasm and nucleus or only nucleus in a few sections. The number of HBcAg and HBeAg expression in hepatocytes was decreased according to the progression to liver cirrhosis. Expression of HLA class I antigens tended to be preferentially stained in serum antiHBe positive patients rather than HBeAg positive ones. Moreover, the lesser display of intrahepatic HBcAg and HBeAg tended to correlate the greater display of HLA class I antigens. These findings suggest that HLA class I antigens as well as HBcAg and HBeAg in hepatocytes play a role in the immune response to HBV-infected hepatocytes.

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As pattern of hepatic cell necrosis in patients with chronic hepatitis (CH), focal necrosis, piecemeal necrosis and bridging necrosis have been reported. However, little is known about submassive necrosis appeared during the course of in CH. Four patients (2, CH type B, 1, CH type non-B, early liver cirrhosis), were examined by peritoneoscopy and liver biopsy, before and after severe exacerbation (total bilirubin 26.7±18.3mg/dl, GOT 1053±943 IU/l, Normo test 16±4.7%). All cases were negative for IgM anti-hepatitis A virus antibody. And, in 3 cases with HBs antigen positive chronic liver diseases, activity of HBV-DNA polymerase increased and anti-δ antibody was negative, anti-HBe antibody was positive.
Histological study of the liver biopsy specimens taken from the liver after the exacerbation showed the presence of submassive necrosis and rosette formation of liver cells. These liver were progressed to postonecrotic liver cirrhosis. Our observations clearly demonstrate that the patients with CH having submassive hepatic necrosis developed atrophic liver cirrhosis, later.

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Prevalence and clinical significance of anticentromere antibodies (ACA) was investigated in sera of the patients with autoimmune liver diseases. We tested 16 sera from patients with lupoid hepatitis (group I), 22 sera with primary biliary cirrhosis (PBC) (group II), 4 sera with Sjogren's syndrome (SjS) withdut liver dysfunction (group III), and 60 sera with non-autoimmune chronic liver diseases (group IV). We found ACA in 2 patients (12.5%) in group I, in 6 patients (27.3%) in group II, but in none of the patients in group III and IV. SjS were complicated in 5 of 8 patients (62.5%) positive for ACA. CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia) was not revealed in any of those positive for ACA. Prevalence of ACA was higher in patients with PBC whose sera had low titer (less than 1:160) of antimitochondrial antibody (AMA) or no AMA. There was no patient with jaundice in those positive for ACA and their histological findings of the liver were mild. ACA was highly frequently detected in autoimmune liver diseases with SjS but not in SjS without liver dysfunction. It is suggested that ACA could be implicated in the pathogenesis of or as an epiphenomena of some group of autoimmune liver diseases.

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Changes of the activity and localization of alkaline phosphatase (ALP) were studied in primary cultured rat hepatocytes.
The activity of ALP slowly increased after isolation and reached a plateau by 48 hours. This increment was thought to have been resulted from the functional recovery after the hepatocytes regained cell to cell contact and also from the obstructive effect on the newly formed bile canaliculus under monolayer culture.
The histochemical studies revealed that the localization of ALP was shifted along with the change in the direction of transcellular mobilization of materials across the hepatocyte.
Addition of taurocholate and taurodeoxycholate into the culture medium resulted in enhanced activity of ALP with increased reaction products in the endoplasmic reticulum.
These findings suggest that ALP has a primary role for the transportation of materials across the hepatocyte and the elevated serum level of ALP in cholestatic diseases is partly explained by the induction of ALP by bile acids which accumulate much in the serum during cholestasis.

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Small liver specimens obtained by biopsy from patients with chronic liver diseases were solubilized to determine the asialoglycoprotein receptors (ASGP-R). ASGP-R in the liver from patients with chronic active hepatitis were 52% of the control and 27% in the cirrhotic liver, respectively. The receptors were negligible in tissues from patients with either hepatocellular carcinoma of metastatic tumor.
Asialoglycoproteins (ASGP) in the serum of the patients with these chronic liver diseases increased with the progression of the disease. There was a significant reciprocal correlation between the amounts of serum ASGP and ASGP-R in the liver (r=-0.705, p<0.001), indicating that the marked accumulation of ASGP in the serum observed in the patients with chronic liver diseases was ascribable to the decrease of ASGP-R in the liver.
Serum ASGP correlated well with the values of several tests which are considered to indicate the hepatic functional reserve such as ICG-R₁₅, prothrombin time, hepaplastin test, choline esterase and E/T cholesterol. It was concluded that the measurement of the serum ASGP could be used as a liver function test to estimate the hepatic functional reserve of the patients with chronic liver diseases.

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To differentiate the small hepatocellular carcinoma (HCC) from other hepatic tumors by US, in 6 resected HCC smaller than 2cm in diameter, we compared ultrasonographical findings with histological findings.
The results of this study are as follows:
1) Histological septal formation (83.3%) and lobulation (66.7%) can already be seen in the small HCC.
2) Ultrasonographical "septum in nodule" and "nodule in nodule" appearance are in good agreement with histological fibrous septal formation and lobulation. It appears as a hyperchoic septum if the septum course vertically to the beam of ultrasound, and appears as a hypoechoic septum if the septum is curved to the beam of ultrasound.
3) From a cubic structure with serial cut surfaces, fibrous septal formations were due to the penetration of a fibrous capsule. After penetration of fibrous capsule by malignant tissue, the penetrated fibrous capsule remains in the nodule as a septum.
4) In the nodular small HCC with septal formation, the 7 characteristic findings in HCC larger than 15mm can be detected, especially, "septum in nodule" and "nodule in nodule" appearance are most important findings to differenciate small HCC from other malignant or benign tumors.

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To examine the influence of transcatheter hepatic-arterial embolization (TAE) to host immune response, natural killer (NK) activity of the peripheral blood was underwent before and after TAE in patients with hepatocellular carcinoma.
NK activity decreased significantly (p<0.01) from 32.4±12.4% to 24.6±12.2% within a week after TAE, and this depression of NK activity continued for a month. In order to examine the influence of adherent cell, NK actitivy of the non-adherent peripheral blood mononuclear cells (PBMC) was compared with NK activity of whole PBMC after TAE. In 7 cases of 11 cases (63%), NK activity of the non-adherent PBMC was higher than that of whole PBMC. These results suggested that the suppressor activity of adherent cells was one of the cause of the depression of NK activity after TAE. After clinical administration of OK432, biological response modifier, supressor activity of the adherent cells to NK activity was disappeared.

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We investigated the immunolqgical characteristics in patients with hepatocellular carcinoma (HCC) and treated them with autologous lymphokine activated killer (LAK) cells and recombinant interleukin 2 (rIL-2). We observed the following points:1) LAK activity was very low in all cases of HCC, 2) Impaired LAK activity was remarkably augmented by systemic administration of rIL-2, 3) LAK cells induced at high concentrations of rIL-2 (≥150 ng/ml) maintained high activity for 48 hours in the rIL-2 free medium.4) After LAK administration, mononuclear cells which were collected from surgical specimens of the HCC mass were found to be cytotoxic against autologous fresh HCC cells. On the basis of these findings, we transferred 1-10×10⁹ LAK cells once or twice a week along with a daily administration of 15 μg rIL-2 to 11 patients with advanced HCC. In result, a more than 35 percent reduction of serum α-fetoprotein (AFP) was observed in 4 of 10 cases and a decrease in tumor size was observed in 2 of 11 cases without any serious side effects except for fever and eosinophilia.

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Serum Cu, Zn-SOD concentration and histological localization of patients with HCC were examined using anti-human Cu, Zn-SOD monoclonal antibody. The serum Cu, Zn-SOD concentration of patients with HCC was significantly elevated compared with healthy adults and also patients with liver cirrhosis but there was no correlation between serum Cu, Zn-SOD and serum GPT, GOT, AFP values.
There are many reports that diminishing amounts of Cu, Zn-SOD activity were found in tumors, but our histological results show that in about 20% of our specimens Cu, Zn-SOD was strongly stained in tumors.
This may indicae that amounts of Cu, Zn-SOD were quantitatively increased in tumors.
These results suggest that it is possible for Cu, Zn-SOD to be a new marker for HCC and a possible reason for the existence of anti-cancer drug resistant HCC, for example such as adriamycin which kills the tumor cells mainly with active oxygen.

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In order to clarify the metaboiic fate of chenodeoxycholic acid (CDCA), the changes of bile acid levels in bile and in serum were determined after the oral administration of 11, 12-2H-CDCA, and kinetic parameters were analysed by isotope dilution method. Kinetic parameters of CDCA found in healthy Japanese aduits are fairiy good agreement with the reports of Western reseachers. Furthermore, each parameter obtained from bile was readily identical with that obtained from serum, respectiveiy, suggesting that bile acid kinetics in human can be determined with serum samples in place of biie.
In a case of cholelithiasis, reduction of the pool size and increase of the fractional turnover rate were observed. In patients of intrahepatic cholestasis, a marked reduction of CDCA pool size ahd its synthesis rate were observed. In patients with cirrhosis, the pool size was about three quarters and the synthesis rate was one-half that of the healthy adults.

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This study was based on our model of experimental autoimmune hepatitis produced by immunizing C57BL/6 mice with syngeneic liver antigen and Freund's complete adjuvant (FCA). Moderate mononuclear cell infiltration occures in the liver in these hepatitis mice. When lipopoly- saccharide (LPS) were intravenously injected into the mice with hepatitis (25μg/mouse), about 60% of the animals died within 48 hours of the injection. Histological changes of the liver were very severe, with extensive hepatocyte necrosis and mononuclear cell infiltration. The serum lactate dehydrogenase and asparatate aminotransferase levels were markedly elevated. Histological changes of other organs were much milder compared to those of the liver. By contrast, the same dose of LPS did not induce severe hepatic changes in normal mice.
These results seem to indicate that acute hepatic failure is induced by LPS in the mice with pre-existing hepatitis and that infiltrating mononuclear cells in the liver play an important role in this process.

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A boy aged 2 was reported that anti-HBc had been negative in spite of HBV carrier caused by vertical transmission. No liver dysfunction was observed after birth. It was supporsed that HBV transmitted transplacentally in utero, because:
1) HBs antigen was positive within the first week of age.
2) HBV-DNA was positive in umbilical cord blood.
Though the father showed normal response of anti-HBc after acute hepatitis B, the mother revealed low level of anti-HBc at the labor (62.7%, RIA) and 2 years after the labor (78.0%). Genetic abnormality might be suggested about the lack of anti-HBc in patient.
On immunological examination, no abnormality was indicated for the mother but low titer of IgA and decrease of the population of OKT4 cell and OKT4/8 ratio were pointed out in the patient.
This paper suggests the pathological role of anti-HBc in HBV infection, especially transplacental transmission in utero.

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A 39-year-old-woman with fulminant hepatitis is presented. Since 20 years of age, she had habitual use of bromides, 20 tablets daily, because of severe menorrhalgia and headache. In 1982, headache and convulsion had developed. Computed tomography (CT) revealed brain atrophy. Since then, she took Sedes A as much as 40 tablets daily.
In 1985, she felt general fatigue, abdominal pain and diarrhea. Laboratory data revealed severe liver dysfunction and prolonged prothrombin time. Then she was transferred to our hospital with suspicion of fulminant hepatitis in August 18. Plasma exchange and glucose-glucagon-insulin therapy were effective. In 12th hospital day, she had Jacksonian's type convulsion attack. Brain CT showed the atrophy of bilateral frontal lobes. The cause of the hepatic failure was thought to be due to acetaminophen over-dose because both IgM-type of anti-HBc and anti-HA were negative. Long-term bromides overdosage might be an underlying etiology of her brain atrophy.

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A clinical case of portal vein infection leading to fatal intra abdominal heamorrage in a 74 y/o male acute myelogenic leukemia patient.
Spontaneous rupture of the liver is an uncommon entity. Misdiagnosis and late treatment contribute to the high mortality rate, 80% or over. Spontaneous rupture of the liver occurs in the following situations. Rupture from the hepatomas, rupture of the liver in a pregnant woman in the third trimester, and bleeding from peliosis hepatis.
This report is the first case of portal vein infection, leading to spontaneous rupture of the liver and death. The patient was a luekemic patient under treatment, who had been immuno suppressive state.

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We present a case of acute hepatic failure which developed in the 2nd trimester of pregnancy, that was difficult to diagnose clinically and histologically.
The patient was a 20-year-old female gravida II, in the 21st week of pregnancy. She had symptoms relating to a common cold followed by jaundice in the 23rd week. Upon admission, she had already suffered from DIC, acute hepatic failure as well as other multiple organ failure. After admission, her condition deteriorated and she expired in the 24th week of pregnancy. From the clinical course and findings, as acute fatty liver of pregnancy was suspected.
Autopsy findings revealed multiple infarction with hemorrhage in the cut surface of the liver. Massive coagulative necroses of the hepatocytes with fibrin thrombi, suggesting circulatory disturbance, were observed histologically. Although the microvesicular fatty droplets, that are characteristic of acute fatty liver of pregnancy, were sparsely seen in the hepatocytes. Multiple coagulative necroses with fibrin thrombi were also seen in the glomeruli, both lungs, adrenal glands, and the bone marrow.
In several previous papers, the possible relationship between Shwartzman phenomenon and acute hepatic failure with DIC was discussed. In this case we considered that the acute hapatic failure was caused by the Shwartzman phenomenon.

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