An investigation on the risk of HB virus (HBV) related to liver diseases was made using a cohort of 32, 177 healthy male workers aged 40, 45 and 50 at the beginning of the study, during 7 years from 1973 through 1979. Of them, 495 (1.5%) were regarded as HBsAg carrier. These were followed up with HBV markers and liver function tests at least twice a year. The folow-up periods were 4 to 10 years with average 5.5 years. The determination of HBsAg was made by RPHA and anti-HBc by IAHA.
During the follow-up period, HBsAg-natural-negative-seroconversion was detected in 19 of the 495 carriers (3.5%). The annual seroconversion rate was 0.69% (person-years). The rate increased with aging. There were highest rate (1.07%) at 50 to 54 age.
Anti-HBc titers (2n) were compared between the 1st and the last tests in the 19 HBsAgnegatively-seroconverted cases (NCC) and the 476 remaining persistent HBsAg positive cases (PPC).
The average titer levels of anti-HBc in NCC were 12.8±1.6 at the 1st test and 9.5±1.9 at the last test, and in PPC respectively 12.6±1.9 and 12.0±2.1. The NCC revealed a significant fall on anti-HBc titer at last test in comparison with the 1st test. It was also shown in the last test of the PCC. Of 19 cases, 14 showed normal liver function tests and 5 were abnormal. But these 5 cases showed only mild liver dysfunction.
These results reveal that HBV naturaly have been cleared from body in Some cases of HBsAg carrier. Further Studies will be required to conclude whether the HBsAg-negativeseroconversion in HBsAg carrier has prognostic significance in the course of liver diseases.

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Using our model of experimental autoimmune hepatitis that developed in C57BL/6 (B6) mice following immunization with syngeneic liver antigens, regulation of helper and cytotoxic killer T cells by suppressor T cells in the spleen and liver of hepatitis mice were investigated. It was found that helper T cells in the nylon wool column non-adherent fraction of cells from the spleen and liver were under clear control by suppressor T cells. The results of an in vitro cytotoxic assay suggested that two different types of cytotoxic killer T cells were operative against target liver cells. One of them had a characteristic to adhere to nylon wool and was under a weak control of suppressor T cells. Another kind of cytotoxic killer T cells did not adhere to nylon wool and was strongly controlled by suppressor T cells. These findings suggest that immunoregulatory mechanisms play an important role in the induction of hepatitis in our model.

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The effects of OK-432 (streptococcal preparation) on murine fluminant hepatitis were investigated. Hepatitis was induced by injection of mouse hepatitis virus type 2 (MHV-2) at a strength of either 1×10³ or 1×10⁴ plaque forming units (PFU). Mice without OK-432 treatment died Within five days, whereas after 60 days mice preinoculated With OK-432 showed survival rates of 50%(1×10³ PFU) or 10% (1 × 10⁴ PFU). Survival time was not prolonged if OK-432 was injected after MHV-2. Examined histologically mice untreated with OK-432 showed severe hemorrhagic necrosis of the liver, often panlobular. Treated mice showed less necrosis; the least necrosis was observed in those injected with OK-432 before MHV-2. In 7-day survival mice injected first with OK-432 and then with 1×10³ PFU of MHV-2, autopsy showed a very slight and focal hepatic necrosis with follicular infiltration by lymphocytes and macrophages.

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Clinical and histological features in 8 cases with severe alcoholic hepatitis (SAH) were analysed and compared with those in 65 cases with non-severe alcoholic hepatitis (AH).
All of 8 cases with SAH had less than 50% of prothrombin value, 7 cases with SAH showed hepatic encephalopathy and 7 cases died of complications such as pneumonia, renal failure and gastro-intestinal bleeding within one month after the abstinence.
All cases with SAH showed remarkable hepatomegaly above 2 FB under the right costal margin and leucocytosis above 10, 000/mm3.
4 of 7 cases with SAH had fever, elevated serum BUN and creatinine levels.
Endotoxemia was found in all cases with SAH examined.
Circulatory immune complex was also frequently detected in cases with SAH.
Hepatic scintigram using 99mTc-Phytate showed remarkably decreased hepatic uptake of radioisotope in cases with SAH.
It was suggested that SAH had depressed reticulo-endothelial function which resulted in endotoxemia and multiple organ failure.

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We investigated eight cases of latent cirrhosis (7 males and 1 female, 47.4±11.3 yo, 1.9% of all cirrhotic patients) which showed normal liver function tests. Most cases were positive for serum HBsAg and anti-HBeAb. All patients showed good hepatic reserve and none of them had esophageal varix, while two cases were associated with hepatocellular carcinoma. Ultrasonography and RI scintigraphy revealed uneven echo level or RI distribution in the liver in most cases, and definite SOL in the liver in both patients with hepatocellular carcinoma. Histopathological study showed inactive cirrhosis or early stage of liver cirrhosis.
From these findings, it is important to perform ultrasonography and RI scintigraphy as screening tests and also peritoneoscopy and liver biopsy, even if their liver function tests were nomal, particularly in the cases of middle and old-aged HBsAg carriers.

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The activities of the interferon-induced enzyme 2'-5' oligoadenylate synthetase in peripheral blood mononuclear cells (PBMCs) and serum were detemined by column method and radioimmunoassay (RIA). The levels of this enzyme activity in PBMCs by RIA correlated well with those by column method (r=0.86, p<0.01). The levels of this enzyme activity in serum by RIA paralleled those in PBMCs (r=0.43, p<0.05). The levels of this enzyme activity in PBMCs were significantly increased in patients with chronic hepatitis type B(p<0.05). The activities of the enzyme in PBMCs and serum were determined in patients with chronic hepatitis type B during the treatment of interferon-β. The levels of this enzyme activity were increased in PBMCs and serum, and the degree of this increase correlated well with the antiviral effect. The data showed that determination of this enzyme activity in serum by RIA is useful to observe an endogenous interferon response and anti-viral state during interferon treatment.

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Decreased insulin binding has been reported in various liver diseases. But its mechanism could not be clearly delineated. To address this problem, IRI levels before or after 10min of IV glucose load, glucose tolerance curve and insulin binding to liver 40, 000g pellets were measured in rats with normal, CCl4 induced acute and chronic liver injury. IRI levels before or after IV glucose load were highest in acute liver injury, higher in chronic liver injury than in normal. Abnormal glucose tolerance was suspected in acute and chronic liver injury after IV glucose load. Specific insulin binding was lowest in acute liver injury, lower in chronic liver injury than in normal. Scatchard plots revealed that its decrease in acute and chronic liver injury was mainly due to reduced binding sites. From these results, we conclude that the decreased insulin binding exists probably as a consequence of hyperinsulinemia.

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Hanganutziu-Deicher (H-D) antibody activities in the sera of patients with various liver diseases were examined by the enzyme immunoassay (EIA) using high molecular weight glycoprotein (HMWGP) as H-D antigen.
Mean O.D. values of IgG class H-D antibodies were significantly high in CH, LC and HCC patients as compared with normal individuals. On the other hand, the mean O.D. values of IgM class H-D antibodies was significantly high in LC patients alone. The positive percent of IgG class H-D antibodies was 5.7% in AH, 28.1% in CH, 21.9% in LC and 26.9% in HCC, increasing as the illness progressed. There was no difference in the incidence of positive IgM class H-D antibody among the liver diseases studied.
H-D antibody activities in patients with chronic liver diseases did not change during their clinical courses, whereas those of patients with AH decreased with improvement of their illness, and out of seven HCC patients subjected to transcatheter arterial embolization, the H-D antibody activities increase greatly in two. H-D antigens were not detected in liver disease sera, but these results suggest that infection with hepatitis virus or necrosis of hepatic cells might stimulate the formation of H-D antibodies.

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Human liver tissues were cracked in isopentane cooled by liquid nitrogen followed by immersion in 0.5% Triton X-100 or were perfused with 0.5% Triton X-100 and then fixed. Liver tissues were investigated by transmission and scanning electron microscope. Numerous intermediate filaments, a few microtubules and many microfilaments were noted in the cytoplasm of hepatocyte in situ. Three dimensional filamentous networks were visualized which were more prominent around bile canaliculi and at cell borders. Many microfilaments were preserved in the materials which were cracked in the isopentane at first. These results indicate that these methods are very useful to investigate cytoskeletal pathology of liver diseases.

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The livers of 40 Wild woodchucks were examined pathologically. In woodchuck hepatitis virus (WHV)-positive 29 animals, all animals had lesions characteristic of viral hepatitis (28 of these had chronic persistent hepatitis occasionally associated With ground-glass hepatocyte and one had chronic active hepatitis) and 26 had Shikata's orcein positive staining. In such cases, formation of filaments, enveloped particles and aggregation of noncoated core particles were found in the cytoplasm of hepatocyte under the electron microscopy. 18 of animals with WHV infection had hepatocellular carcinoma associated with chronic persistent hepatitis and hyperplastic foci of hepatocyte. In addition, 7 animals without hepatocellular carcinoma had also hyperplastic foci.
These hyperplastic foci were considered as potential precursors of hepatocellular carcinoma, and the results suggested that woodchuck hepatoma may develop multicentlic. On the other hand, in WHV negative 11 animals, there were no significant pathological changes. 7 of 40 animals had parasitic infection (6 had C. hepatica and one had T. mustelae) in the liver.

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Histochemical examinations, mainly keratin staining, three types of antibodies including polyclonal, KL-1 and PKK-1, were performed on combined hepatocellular-cholangiocarcinomas (9 cases), hepatocellular carcinomas (21 cases), intrahepatic cholangiocellular carcinomas (11 cases) and normal liver (5 cases). "Mixed type, subtype" was added to Allen's classification of combined hepatocellular-cholangiocarcinomas, two cases corresponded to the additional subtype. Intracellular keratin staining patterns were classified into four types, and intracellular keratin localizations of combined hepatocellular-cholangiocarcinomas, hepatocellular carcinomas and cholangiocellular carcinomas were clarified. In the intermingled area of the mixed type, there was an admixture of the tumor cells showing hepatocelluar carcinomatous and cholangiocellular carcinomatous keratin patterns, respectively.

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Two cases, case 1, 70 and case 2, 31 years old male, of nonhemolitic unconjugated hyperbilirubinemia associated with remarkable retention of both ICG and BSP excretion are presented.
Both cases had had hepatitis about 20 years ago. Laboratory examinations including transaminase and alkalin phosphotase were normal except for high serum unconjugated bilirubin (about 2mg/dl), remarkable ICG retention (R₁₅ about 80%) and BSP retention (R₁₅ about 18%) in both cases. Case 1 had slightly shortened red cell turnover rate (⁵¹Cr-RBC T1/2 22.5 days) and chronic inactive hepatitis in his liver biopsy specimen. Case 2 had normal red cell turnover rate and normal liver histology.
The analysis of ICG curve and BSP conjugates suggested abnormalities somewhere from dye uptake to transfer mechanism, and slightly disturbed excretion. Although the influences of hepatitis can be completely excluded, these cases seem to have new type of constitutional hyperbilirubinemia.

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A 24-year-old female suffered from Primary biliary cirrhosis (PBC) after delivery is reported. She was admitted to Toyokawa City Hospital following general fatigue and abdominal pain. The laboratory data reported a high level of serum ALP, LAP, γ-GTP and IgM. Antimitochondrial antibody was positive. Histological findings of liver biopsy indicated infiltration of lymphocytes and epithelioid cells and the bile duct epithelium with degeneration and disappearance in the portal area. Therefore we diagnosed PBC. Oral administration of predonisolone (20mg/day) brought her marked improvement of laboratory data. The cases in association with PBC, pregnancy and delivery have been rarely reported. Recently it is said the young patients of PBC are increasing, so it is important to investigate the infuluence of pregnancy and delivery on PBC.

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A case of sclerosing hepatic carcinoma with a long-term preoperative elevated α-fetoprotein showing good postoperative course was reported. She was a 57 year-old woman who had no complaints and no abnormalities of the liver function tests except a remarkably elevatedα-fetoprotein of 10, 140ng/ml. During the 2 year observation, no tumors producingα-fetoproteins had been recognized. The tumor was found in the left lateral lobe of the liver on ultrasonography and CT-scan after 2 years observation. She was recieved the operation of left lobectomy of the liver Dec 3rd, 1982.
The pathological findings revealed the caracteristics of the sclerosing hepatic carcinoma (SHC), acampanying, in parts, the lamellar fashion of fibrosis, so-called fibrolamellar carcinoma. This case looked different from SHC in some points, eg without pseudohyperparathyroidism, with good clinical course by far over 3 years after lobectomy.
It is likely that the lamellar fashion of fibrosis may be checked the growth and progress of the SHC.

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The case reported here was a 72-year-old female who had been treated under a diagnosis of liver cirrhosis associated with minute hepatocellular carcinoma and died from hepatic failure. The liver weighed 610g and was atrophic with cirrhotic appearance.
The cut-surface showed four small nodule, measuring 0.7 to 2.5cm in diameter.
Two of them were hepatocellular carcinoma of Edmondson's grade II. The other two nodules were diagnosed as adenomatous hyperplasia and had foci of hepatocellular carcinoma within the nodules (nodule in nodule).
These two types of hepatocellular carcinoma showed different morphology and a stainingpattern of a-fetoprotein.
We reported the present case because such findings as described above may give some suggestions to multicentric origin of hepatocellular carcinoma.

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A 52-year-old man with liver cirrhosis was admitted with a chief complaint of hemosputa.
The α-fetoprotein(AFP)was elevated to 32000ng/ml. The findings of abdominal ultrasonogram, angiogram, plain chest x-ray, and CT scan of the chest revealed the hepatoma with multiple pulmonary metastases. TAE with one shot of intra-arterial infusion of MMC (16mg) was performed and administration of PSK(3g/day)was started. AFP levels decreased below 20ng/ml and pulmonary metastatic lesions disappeared after TAE. The patient remains well 18 months later with no pulmonary lesions, and AFP is within normal limits. The complete disappearance of pulmonary metastatic lesions seemed to be caused by improvement of the patient's immunity, which related with the regression of primary tumor after TAE.
This case suggests that TAE is worth to be done even in the case of hepatoma with metastases.

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