The cytotoxic effect of T and non-T cell fractions on autologous hepatocytes was separately investigated by a microcytotoxity system in 18 patients with chronic active hepatitis. The T cellmediatedcytotoxicity was found to be increased in 9 out of 10 HBsAg positive cases and in 5 out of 8 negative ones. Decreased T cell-mediated cytotoxity was observed, when target hepatocytes that were proved to possess β₂-microglobulin and HBsAg on the cell membrane by mixed hemadsorption test, were treated with either anti-β₂-microglobulin or anti-HBs, or when effector T cell was treated with OKT8 and complement. In addition, in these patients the percentage of OKT3 and OKT8 positive lymphocytes in the liver was significantly higher than in the peripheral blood. These data suggest that cytotoxic T cells play an important role in hepatocellular necrosis and HLA antigen and HBsAg are regarded as target antigens for these T cell.

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When a small amount of lipopolysaccharide (LPS) endotoxin was injected intravenously to mice previously treated with heat-killed Propionibacterium acnes (P. acnes), most of mice died with massive liver necrosis.
To study on the mechanism by which these liver injuries were induced, the adherent cells were isolatd from mouse liver 7 days after intravenous injection of P. acnes and activated with LPS in vitro for 48 hours. The resulting culture supernatant was added to the freshly prepared normal liver cell suspension and the hepatocytotoxic activity in the culture fluid was evaluated by measuring the decrease in protein-synthesis of liver cells.
The liver adherent cells from mice previously injected with P. acnes were activated by a limited amount of LPS and cytotoxic activity was detected in the culture supernatant of the stimulated adherent cells. On the contrary, the adherent cells from normal mouse liver did not produce such cytotoxic factor(s) by culturing with same amount of LPS, althoug they were activated at some extent by higher doses of LPS.
These results suggest that the activated adherent cells in liver may play some role in the induction of liver injury in my experimental system, and that at least two sequential signals may be necessary for full activation of the adherent cells to exhibit their cytotoxic effects.

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Intracranial pressure (ICP) and findings of CT-Scan and EEG were evaluated in 10 cases with fulminant hepatitis.
Results were as follows;
1) Initial ICP level in 10 cases was ranged between 10 and 28mmHg and ICP level was exceeded over 20mmHg in cases with Grade IV or V encephalopathy.
2) Maximal ICP level was significantly higher in fatal cases.
3) Duration from the day developing encephalopathy to the day showing maximal ICP level was significantly shorter in survival cases; 3.8 ± 1.3 (M ± SD) days in survival cases versus 6.0±1.4 days in fatal cases.
4) ICP and EEG were valuable for the evaluation of brain edema.
5) ICP should be monitored at Grade III encephalopathy.
6) When ICP is not monitored, administration of mannitol should be started at the stage of Grade IV encephalopathy.

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Plasma exchange (P.E.) therapy for post-operative hepatic failure was not effective when it was applied to a patient who developed advanced hepatic failure of extreme jaundice and deep consciousness disturbance. Then, P.E. was performed in the early stage of hepatic failure predicted by the activity of lecithin cholesterol acyltransferase (LCAT), an accurate predictor of post-operative hepatic failure. The indicative criteria for P.E. therapy were prescribed in the case: 1) who ceased producing LCAT activity, and 2) within grade 2 (Sherlock) of consciousness disturbance, 3) 35% or more of prothrombin time, 4) less than 10mg/dl of total bilirubin. LCAT activity was a useful indicator for evaluation of effectiveness during P.E. therapy. According to these criteria, 5 cases out of 14 (36%) recovered from hepatic failure and 4 cases (29%) lived more than one month after the first P.E.

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Endotoxin was injected intravenously into the 70% hepatectomized rats during active regenerative phase for the purpose of solving the mechanisms of acute hepatic necrosis which is occasionally observed early after hepatic resection in human cases. In this procedure, we were able to cause marked hemorrhagic necrosis in the residual livers in high frequency. The hepatic necrosis was mostly centrilobular one with microthrombi. However there were only slight hepatic lesions in control groups as well as other two experimental groups such as the group in which heparin was administrated almost simultaneously with injection of endotoxin 48 hours after 70% hepatectomy and the group in which endotoxin was injected 10 days after operation when liver regeneration was supposed to be rather completed. In all the groups, there were only slight changes in all the organs except the liver. From these results, it was interpreted that hepatic necrosis occurrng early after partial hepatectomy might be the univisceral Shwartzman reaction and also that hepatic regenerative state might be the preparative state for the Shwartzman reaction.

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Much attentions have been focused to Ito cells (fat-storing cells; FSC) as cells having the fiber producing activity. We have identified desmin in FSC of rat livers by immunocytochemical techniques using antidesmin antibodies. FSC were precisely observed by this method, even in injured liver. In the present study we attempt to study the relation between FSC and hepatic fibrosis in CCl₄ administered rat livers. In acute intoxication FSC increased in number and in size in necrotizing areas before the appearance of fibrosis, and decreased on the progression on fibrosis. In chronic intoxication FSC increased in fibroplastic areas and were seemed to be performed fibers by the connection of cytoplasmic processes of neighbouring cells. FSC were hardly found in fibrotic bundles. These findings suggested a close relation of FSC to the progression of hepatic fibrosis.

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Intrahepatic pressure was measured using 23 G Terumo Cathelin needles connected to a pressure transducer in 120 patients with liver disease including 32 outpatients without major complications. Transhepatic portal vein, hepatic vein catheterizations and intrahepatic pressure measurements were performed simultaneously in 18 patients. Intrahepatic pressure was significantly correlated with corrected wedged hepatic vein pressure (r=0.90), portal vein pressure (r=0.73), and wedged hepatic vein pressure (r=0.75). Intrahepatic pressure was significantly elevated in patients with cirrhosis (251.5±62.3mmH₂O), and chronic active hepatitis (158.8±77.0mmH₂O) compared with patients with chronic persistent hepatitis (104.6±35.1mmH₂O), acute hepatitis (110.6±36.2mmH₂O), normal subjects (80.9±32.8mmH₂O), and patients with idiopathic portal hypertension (97.1±32.4mmH₂O). Thus, measurement of intrahepatic pressure by thin needle system proved to be a safe and useful diagnostic tool.

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It is now generally accepted that macronodular cirrhosis is most frequently associated with hepato-cellular carcinoma (HCC). In this study, the mode of changes in the intranodular microvasculature was investigated during the course of malignant transformation in macronodular cirrhotic rat induced by 3'-Me-DAB feeding (for 5 weeks on diet containing 0.06%) plus carbon tetrachloride (CCL₄) injection (subcutaneously of 0.2ml/100g bw twice weekly for 14 consecutive weeks). The nodules increased in size with time. Microangiograms of the enlarged nodules showed hypovascularity, which led to adenoma formation by the 7th week after cessation of CCl₄ injection. The second CCl₄ administration, which was started at the 11th week after cessation of the first exposure, produced neovascularity in the nodules, where HCC was disclosed histologically. It is cancluded that macronodular cirrhosis is a precancerous lesion and the intranodular microcirculatory derangement is highly responsible for the malignant transformation.

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Endoscopic sclerotherapy was performed for esophageal varices in 95 patients during the period from 1979 to 1984, with the gratifying results. By this procedure, cure of varicosity was attained in all cases treated for relapsed remnant esophageal varices after direct operation. Varices also disappeared following sclerotherapy in 29 (67%) of 43 patients in inoperable conditions due to marked hepatocellular dysfunction or terminal stage of hepatoma,
Histologic observations were made of the lesions in six autopsied cases and to follow changes after experimental injection of a sclerosing agent in dogs and rabbits, in order to clarify the mechanism of healing of varices by sclerotherapy. The study revealed that acute local inflammation occurs after injection, followed in two weeks by fibrous proliferation within the tissue at injection site. The findings suggest that the fibrosis may produce compression to the affected vein leading to its occlusion with consequent disappearance of the varix.

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Integration of hepatitis B virus (HBV) DNA into genomic DNA was investigated in 34 livers bearing hepatocellular cardnoma (HCC) by Southern blot hybridization utlizing a 32P-labeled cloned HBV DNA as a probe. Integrated HBV DNA was detected in all 9 HBsAg seropositive cases and 3 out of 25 (12%) seronegative cases. The hybridization patterns of HBV DNA were different from each other among these 12 cases.
Integrated HBV DNA was found in 5 noncancerous parts of The liver bearing HCC, and the hybridization patterns were different from those in the corresponding cancerous parts in two of them.
The hybridization patterns of viral DNA were the same among several cancer nodules in two HCC cases with multiple liver tumors, indicating unicentric hepatocarcinogenesis in these two cases.

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Tumor invasion in the portal vein demonstrated by pharmacollogically assisted arterial portography was analyzed in 128 patients with hepatccellular carcinoma (HCC).
Results were obtained as follows;
1) Tumor invasion in the portal vein was noted in 98 cases (76.6%).
2) Tumor invasion in the portal vein occurred more frequently in massive type of HCC than nodular type, which were differentiated on hepatic angiogram.
3) Regression of tumor invasion was in 12.0% by one shot injection of anticancer drugs via the hepatic artery, 20.0% by TAE treatment, and 16.0% by oral administration of anticancer drugs.
4) Bleeding from the gastro-intestinal tract such as hemorrhagic gastritis and rupture of esophageal or gastric varices occurred in 29.4% of cases with tumer invasion in the main portal vein.
These results suggest that pharmacollogically assisted arterial portography is useful to demonstrate tumor invasion in the portal vein which is an important factor in life expectation of patients with HCC.

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A 39 year-old male patient with chronic hepatiris type B was reported, who died of acute hepatic failure of fulminant hepatitis-like clinical features.
He had been diagnosed as chronic inactive hepatitis histologically 6 months before his death. HBV-DNA polymerase activity and HBV-DNA were always positive on several exarninations in spite of anti-HBe persistent positive in serum. HBcAg was also detected in the biopsied liver tissue.
Rapid increases of HBV-DNA polymerase activity and HBV-DNA in serum were followed by marked elevations of serum transaminase and bilirubin levels. Anti-HAV and anti-Delta were negative throughout his clinical course and no history of alcahol intake and drug abuse were recognized.
Acute hepatic failure developed about 4 weeks after the exacerbation. Autopsy revealed an atrophic liver of 695g with massive necrosis of the liver. This observation indicates that HBV active replication is closely associated with liver injury in chronic hepatitis type B.

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A case with primary biliary cirrkosis associated with renal tubular acidosis (RTA) and Sjogren's syndrome is reported. The patient was fifty-year-old female and admitted to the hospital because of weakness of lower extremities and truncal muscle pain. Symptoms of Sjogren's syndrome and primary biliary cirrhosis had been masked. Laboratory examinations revealed that findings of distal and proximal RTA, positive anti-mitochondrial antibody and marked elevation of IgM (3300mg/dl). Biopsy samples revealed that pathological changes of minor salivary glands for Sjögren's syndrome and those in liver for primary biliary cirrhosis were those of early stages. In kidney, there was some infiltration of mononuclear cells in interstitial areas and some deposition of IgM around vessels by immunofluorescence study. Reports on the cases with concomitant these three diseases are rare. However, the finding of mononuclear cell infiltration seen in periductal areas in the liver and the minor salivary glands as well as in interstitial areas of the kidney suggest that the occurrence of these three diseases is based on the same immunological mechanism. RTA is considered to be, at least partly, due to deposition of IgM in the kidney.

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Carcinoembryonic antigen (CEA) is a useful tumor marker for gastrointestinal malignancy. But as for liver cancer, α-fetoprotein (AFP) plays a more signiflcant role than CEA. We have experienced a rare case of liver cancer patient, who showed very high values of CEA and AFP in the sera. The tumor consisted of apparently different two parts, well differentiated adenocarcinoma and poorly differentiated part. This case suggests not only that we must keep in mind the existence of CEA producing hepatoma but also that there may be a interest relationship between fetoprotein and the differentiation.

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The authers have experienced 3 cases of Budd-Chiari syndrome in recent 2 years in 1983 and 1984. The patients were all middle-aged males. Two of them were diagnosed as the primary Budd-Chiari syndrome, obstructed inferior vena cava (IVC) with the membranous webs. While the other one was diagnosed as the secondary Budd-Chiari syndrome with the thrombosis in hepatic veins, pulled IVC towards right frontal side due to the thickend pleura. The authers applied NMR-CT as the diagnostic means. The results and its efficacy were compared with the other diagnostic means, especially with the inferior venocavagraphy. NMR-CT had merits of noninvasive, giving three-dimentional images of the lesions as well as the collateral venous shunts, and it was suggested that this tecknique is a useful means for the diagnosis of vascular abnormalities including Budd-Chiari syndrome.

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