To study the ultrastructural differences of hepatocytes between patients with each type of viral hepatitis, morphometric analysis was performed by an image analyser of Digigramer G. Patients included were 9 with type A hepatitis, 8 with type B hepatitis, 8 with non-A, non-B posttransfusion hepatitis (NANB-PTH), 8 with non-A, non-B sporadic acute hepatitis (NANB-SAH) and 8 cases with normal liver (control). Liver biopsies were done blindly or under peritoneoscopy for hepatitis patients and surgically for control by operation of non-hepatic diseases. Mitochondrial isoenzyme fractions of GOT (m-GOT) in sera of patients with hepatitis were also investigated and they were compared with the morphometric findings.
The ratios of mitochondrial to hepatocytic area and of mitochondrial to cytoplasmic area were smaller in NANB-SAH than in type A hepatitis (p<0.05). Number of mitochondrion in a hepatocyte was lesser in NANB-SAH than in control (p<0.01). Mitochondrial changes were different in each type of viral hepatitis and these might be attributed to the difference of hepatitis viruses. However, no relationship between mitochondrial changes and m-GOT levels in acute viral hepatitis could be observed, which might be due to the functional and morphologic difference of hepatocyte injury in viral hepatitis.

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Prolonged (more than 2 years)e-window state was observed in 17 hepatitis B patients. Histological studies of these 17 patients showed that their liver diseases are advanced. Their histological diagnoses are liver cirrhosis in 6, chronic aggressive hepatitis (2B) in 8, chronic aggressive hepatitis (2A) in 3. Our study divides the patients into group A and group B, group A having HBs readings of 2² and less, and group B having readings which fluctuate 2³-2¹². In six of the eight patients in group A, RPHA tests revealed a disappearance of HBsAg, RIA tests revealed a disappearance of HBsAg in 5 of these 6 patients. Serum GPT levels were normal in five of the eight patients in group A, and up to 100 K.U in three of them. However in 14 patients from group B, serum GPT levels fluctuated between normal andmore than 100 K.U. We conclude from our study that prolonged e-window state may be observed in patients with advanced liver disease, but that among them there are cases who eliminate hepatitis B virus and improve liver function.

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Large doses of recombinant interleukin-2 (rIL-2) were administrated to 8 patients with hepatitis B e antigen (HBeAg) positive chronic hepatitis B. DNA-polymerase (DNA-P) activity was detected in the sera of 6 out of 8 cases. They received a constant dose of 30 ng/day intravenously for consecutive 7 days.
DNA-P activity showed gradual decrease in all patients and turned negative in 2 out of 6 cases at the end of the treatrnent. It remained nagative only in one case for a week after the treatment. But the concentration of hepatitis B s antigen (HBsAg) and HBeAg was not affected by rIL-2 administration.
Investigation of immunological effects in these patients showed a transient decrease of Leu7+ population number and an increase of OKT4/OKT8 ratio in the peripheral mononuclear cells. But neither HBsAg specific cytotoxic Tcell activity, natural killer activity, nor lymphokine activated killer activity were augmented. PPD stimulated and PHA stimulated T cell blastformation were not affected.

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The effect of epidermal growth factor (EGF) on acute hepatic failure was examined. We administered total 3μg of recombinant human EGF in three divided intraperitoneal injections to the rats which had been given 1600mg/kg or 1000mg/kg of D-galactosamine (D-gal.). The survival rate at ninety-six hours after D-gal. administration was 75% in group I (given EGF at-12, 0 and 12 hours after D-gal. administration), while that was 25% in group II (given EGF at 12, 24 and 36 hours after D-gal. administration) and group III (given no EGF). The peak values of serum GPT (mean±SD U/1) in groups I, II and III were 2393±1492, 3614±2914 and 8297±4746, respectively. Microscopic examination of excised livers showed the histopathological improvement in groups I and II compared with group III.
From these findings, it is suggested that EGF may suppress the progression of hepatic necrosis and improve the survival rate in acute hepatic failure, particularly when it is given at early stage of liver injury.

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We have studied the incidence of the different submitochondrial antigen (anti-M₂ and anti-M₄) and clinical significance of prominent piecemeal necrosis (PN) in 13 primary biliary cirrhosis (PBC), stage I or II in differentiatimg "mixed form" of PBC and chronic active hepatitis (CAH) from classical PBC. The patient consists of 3 men and 10 women with a mean age of 57.1 years. All the caseS had histological lesions of chronic nonsuppurative destructive cholangitis. Moderate to severe PN was seen in 8 and bridging necrosis in 6. Granuloma was encountered in all the cases without PN, but in 3 of the 8 cases with PN. Antimitochondrial antibody (AMA) was positive in all the cases and PBC-specific AMA (anti-M₂) was also positive in all but one. Anti-M₂ and anti-M₄ were both positive in 2, in which prominent PN was noted in one. Therefore, the incidence of simultaneously positive anti-M₂ and anti-M₄ was low eveh in the "mixed form" of PBC and CAH. Simultaneous increases in IgM and IgG were prominent features in PBC with PN. SGOT predominated SGPT in PBC with PN, while SGPT predominated SGOT in PBC without PN.

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One course of sclerotherapy or percutaneous transhepatic obliteration were performed to cirrhotics with esophageal varices electively or prophylactically, and we calculated the cumulative survival rate and the cumulative bleeding rate of esophageal varices and upper gastrointestinal tract up two years after treatment. Comparing with PTO group, both elective and prophylactic sclerotherapy groups show better survival rate and lower bleeding rate. Serial endoscopic findings indicate that esophageal varices are developed six months after eradication and gradually grow up. Low grade fever and microscopic hematuria are occured accompanied with sclerotherapy but there is no lifethreatening complication. Sclerotherapy is advocated as the first line of treatment for cirrhotlc patients with ruptured varices or non-ruptured risky varices.

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Anhepatic stage in livertransplantation are accompained by various coagulation disturbances. Coagulation changes during the anhepatic stage were investigated in hepatectomised dogs. Animals were divided into 3 groups; Group I with total hepatectomy under the V-V bypass using pump without heparinization, Group II with V-V bypass only and Group III with splenectomy only. The platelet count was stabilized in Group III but decreased significantly in Groups I and II from 30 minutes after start of V-V bypass. Prothombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged in Group I from 30 minutes and 3 hours respectively after V-V bypass start, compared to Group II. The platelet aggregability was diminished with time in Group I, but stayed unchanged in Group III. The fibrinogen degradation products (FDP) were positive in 40% of the Group I dogs at 30 minutes after V-V bypass start but became positive in 100% at 3 hours. The positive ratio in Group III did not change with time. Analysis of the coagulation changes by V-V bypass suggested that at the anhepatic stage, plasma clotting factor deficiencies occur relatively early with the appearance of FDP to result in coagulation disturbances.

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Morphometric analysis of sinusoidal endothelial fenestration (SEF) of rat liver was carried out in five degrees of perfusion pressure (5, 10, 20, 30, 50cmH₂O) via the portal vein using scanning electron microscope. In the perfusion pressure at 10cmH₂O, the diameter of SEF in zone 1 was significantly (p<0.001) larger than that in zone 3. The number of SEF in zone 3 was significantly (p<0.001) larger than that in zone 1. The area of SEF per square micron of the endothelial surface in zone 3 was significantly (p<0.05) more than that in zone 1. The SEF having more than 300nm in diameter was noted very infrequently in zone 1 and zone 3, which increased with the rise of perfusion pressure. The size of SEF might be easily changed by the sinusoidal pressure. These results indicate that in the hepatic lobule there is heterogeneity in the number, the diameter and the area of SEF. The present results are important for the investigation of SEF in various kinds of pathological conditions in the liver.

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The innervation of the human liver was investigated by the electron microscopy. In the portal area, unmyelinated nerve bundles were found close to the fibroblasts with collagen fiber around the portal vein, bile duct, hepatic artery, and lymph vessel. Moreover, the Schwann cells with many axons were found in the portal area.
In the mid-zonal area of the lobule, unmyelinated nerve bundles were found running between the Ito cell and the hepatocyte, and also between hepatocytes. The varicosities appeared to face the Ito cell or hepatocyte across a synaptic cleft.
Moreover, the varicosities showed in direct contact with hepatocytes. The collagen bundles were found close to the Ito cells or hepatocytes.
In the centrolobular area, the longitudinal axons were found between hepatocytes near the central vein. Moreover, small unmyelinated nerve ending faced the myofibroblast across a synaptic cleft, and the endothelial cell by way of the basal lamina.
In addition, the varicosities of the nerve ending in the human liver contain many small agranular and granular vesicles, large dense core vesicles, and also many cytoskeletons. It is suggested that the adrenergic innervation exists in the human liver. Moreover, it is suggested that nerves in the human liver have a close relation with intrahepatic vessels or cells, and especially contribute to the contraction of the fibroblast, Ito cell, or myofibroblast around the vessels in the portal area, sinusoid, or central vein.

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A 21-year-old female, had experienced skin eruption for one month, was admitted to a clinic with general fatigue, anorexia, nausea and jaundice. Two weeks after the peak of transaminase levels, high fever and wine colored urine were recognized and serum hemoglobin concentration decreased to 2.0 g/dl. Then, she was received blood transfusions and refered to our hospital. Acute viral hepatitis type non-A, non-B was most suspected because of negative IgM-antiHA, HBs antigen and IgM-antiHBc. Laboratory examinations disclosed severe anemia, reticulocytosis, marked elevation of LDH (LDH1: 37.3%) and marked decrease of haptoglobin, but negative direct Coombs test. Bone marrow showed erythroid hyperplasia. From these findings, the diagnosis of hemolytic anemia was made. She recovered with conservative therapy alone. We reviewed similar cases reported inJapan and discussed some mechanisms of the hemolysis.

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104 Cases of HBe antigen positive chronic hepatitis were treated with corticosteroid withdrawal therapy.
In three cases icterus was observed.
Case 1 : 58-year-old male. In spite of liver cirrhosis, he was treated with corticosteroid withdrawal therapy. After one month ascites and icterus (T. bil 12.0 mg/dl) were observed. After two months HBe antigen disappeared and after one year HBs antigen disappeared.
Case 2 : 42-year-o1d male with HBe antigen positive chronic aggressive hepatitis (CAH2B) was treated with corticosteroid withdrawal therapy. After one year icterus (T. bil 10.0 mg/dl) was observed and HBe antigen disappeared.
Case 3 : 40-year-old male with HBe antigen positive chronic aggressive hepatitis (CAH2B) was treated with corticosteroid withdrawal therapy. After 11 months icterus (T.bil 11.1 mg/dl)was observed and HBe antigen remained persistently positive, In cases of poor liver function, elevated AFP and weak immunosuppression during corticosteroid withdrawal therapy, liver dysfunction can be take a turn for the worst. If there are signs of deterioration, re-administration of prednisolone will be necessary immediately.

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We observed a remarkable reduction of serum α-fetoprotein (AFP) level in a case with advanced hepatocellular carcinoma after adoptive immunotherapy with autologous lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2).
In a therapeutic schedule, 1 to 10×10⁹ LAK cells in a single infusion were administrated intravenously 7 times at one week interval. A total of 3.5×10¹⁰ LAK cells were administrated. Throughout the treatment period of 54 days, 500 U(15μg) of rIL-2 (TAKEDA) was intravenously injected every day.
The serum AFP level in the patient began to decrease at the beginning of the treatment with rIL-2 administration and finally reached to one tenth of the previous value (from 51290 to 4856 ng/ml) with the imjection of LAK cells.
It was suggested that combined adoptive immunotherapy with LAK cells and rIL-2 might be worthwhile in the treatment of hepatocellular carcinoma.

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An autopsy case of a 45-year-old male with hepatocellular carcinoma showing a predominant sarcoma-like feature was reported. The patient was a heavy-drinker and was admitted because of anorexia and abdominal distension. He died of hepatic coma 5 days after admission. Autopsy revealed a large tumor mass, measuring 7×7×5cm in size, in the left lobe of the liver and numerous nodes in both lobes of the liver, both lungs, myocardium and peritoneum. All of the tumors, except in one area, consisted of a loose proliferation of spindle-shaped or round clear cells, Which suggested spindle cell sarcoma. However, well differentiated hepatocellular carcinoma of the trabecular type was shown in a tiny area consisting of three small nodes. The transitional from between hepatocellular carcinoma and sarcoma-like feature was also seen.
Immunohistochemical staining for epithelial membrane antigen (EMA) revealed EMA-positive cells in the nodes showing sarcoma-like feature. Thus it seemed that the sarcoma-like lesion was a variation or an anaplastic change of hepatocellular carcinoma, because of the presence of the transitional form and EMA in the sarcoma-like lesion.

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The patient, 68 years old female, had rheumatoid arthritis for 24 years and splenomegaly was pointed out 14 years ago. Hematemesis due to rupture of esophageal varix occurred two years ago. She admitted to the hospital with a chief complaint of hematemesis. Laboratory examinations revealed; hypergammaglobulinemia, thrombocytopenia, ascites, splenomegaly and positive results of RA, ANA and ASMA. She died of severe pancytopenia. Post mortem examination revealed the atrophic noncirrhotic liver (560g) with thrombosis in the intrahepatic large portal vein, esophageal varicies and splenomegaly (300g). The histology of the liver showed peculiar findings such as; fibrous enlargement of Glisson's capsule with marked canstriction of small portal vein branches, development of ectopic portal vessels, lamellar concentric fibrosis around the bile duct and dislocation of both Glisson's capsule and hepatic vein. No pseudolobule was visible. Immunohistochemical stains failed to demonstrate deposition of immunoglobulins as well as compliments in the liver.
The present case, being compatible with IPH in either the clinical course or the morphology of the liver, suggests that some immunological abnormality, which is common to rheumatoid arthritis, may be related to the development of IPH.

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A 58-year-old woman of primary biliary cirrhosis (PBC) associated with enlargement of lacrimal and submandibular gland, and chronic pancreatitis is reported. The patient was admitted because of cholecystolithiasis and showed elevated IgM and anti-mitochondrial antibody. Surgical liver biopsy revealed chronic non-suppurative destructive cholangitis and simultaneously biopsied pancreas showed diffuse mononuclear cell aggregates, degeneration of acinar cell and fibrosis. The patient complained of slight dry eyes and dry mouth and gradual enlargement of lacrimal gland and submandibular gland were noted. Surgical resection of both glands were performed, histological findings of which were lymphoid infiltration, glandular atrophy, stramal fibrosis and ductular proliferation. These changes are common in systemic glandular tissue, which suggest the presence of "dry gland" syndrome with immunological mechanism in its pathogenesis.

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