In enzyme-liked immunosorbent assay (ELISA) of HBsAg with Hepanostika Microelisa system (Organon Teknika, B.V.) on 1270 sera with negative HBsAg and 40 sera with positive HBsAg, the cutoff value based on the mean absorbance of HBsAg-negative sera was found inadequate in both theoretical and practical aspects. It was more reasonable to subtract the mean absorbance of negative controls as a blank and to obtain a lower detection limit from the standard deviation using a calibration curve prepared with a known standard of HBsAg. The results were reproducible in the revised precedure and could be expressed on a linear scale in absolute quantity. The linear range covered by ELISA was wider than RIA and the assay of samples with higher HBsAg levels could be readily repeated for quantitation by appropriate dilutions.
The HBsAg concentration of human sera distributed in a wide range from 6.7ng/ml to 600μg/ml, and the sera giving HBsAg above 100μg/ml had all positive HBeAg.
A new kit of Hepanostika HBsAg Microelisa system (Organon Taknika, B.V.) had a lower detection limit of 0.3ng/ml, comparable to that of RIA, while keeping a linear range of calibration curve up to 30ng/ml with reproducible results.
Thus, the quantitation of HBsAg by ELISA system may prove to be a clinically useful tool not only in the screening of HBsAg-positive cases but also in the quantitation of HBsAg concentration for followup of HBsAg carriers and treatment of HBV-induced hepatitis.

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Serum levels of N-terminal type III procollagen peptide in normal subjects were determined by radio-immunoassay.
The levels of the peptide are greater in infants from 0 to 3 year age for boys and girls, 8 to 12 year age for girls and 12 to 16 year age for boys than in adults.
This fact seems to suggest that increased levels of the peptide reflect the accelerated collagen synthesis in human body.
Comparison of serum levels of the peptide with the degree of hepatic fibrosis revealed that the concentration of the peptide increased in parallel with the progress of hepatic fibrosis.

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In previous clinical study, we found that the dissociatin between the estimation of galactose tolerance test and ICG Rmax in patients with various liver diseases.
In this paper, galactose tolerance test by rat livers before and at intervals after partial hepatectomy and D-galactosamine (GaIN) injection was compared with ICG Rmax in an attempt to stlldy the correlation between the pathological state of the liver and estimation of tests for functional reserve cell mass of the liver. ICG Rmax paralleled with changes in liver weight after hepatectomy and GaIN injection at intervals for 7 days.
On the other hand, galactose tolerance test did not paraller with changes in liver weight after partial hepatectomy and GaIN injection and rather depended on functional defect of the liver cell due to liver cell necrosis after GaIN injection.
There was indicated that it was the main reason of the dissociation between the setimation of galactose tolerance test and ICG Rmax in clinical study that liver weight never correlated with functional cell mass of the liver.

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The effects of hepatic circulatory disturbance on pathogenesis of hepatic damage and dysfunction induced by endotoxin were experimentally examined, and the below results were obtained. 1) Endotoxin induced focal random coagulative necrosis following accumulation of fibrin and inflammatory cells in the sinusoids and led to marked elevation of serum transaminase levels. 2) Heparin markedly inhibited the above reaction. 3) Thrombin infusion from the portal vein induced focal random coagulative necrosis resembling the lesions induced by endotoxin, following formation of thrombus in the sinusoids, and marked elevation of serum transaminase levels. 4) Endotoxin increased portal vascular resistance, and elevated the portal vein pressure. 5) Partial obstruction of the portal vein induced reduction of portal venous blood flow, and led to the elevation of serum transaminase levels without hepatic necrosis. 6) Endotoxin infusion from the portal vein following partial obstruction of the portal vein induced focal random, zonal and massive hepatic necrosis, as well as marked elevation of serum transaminase levels.
These results suggest that hepatic necrosis induced by endotoxin is attributed to circulatory disturbence of the sinusoids resulted from the formation of fibrin thrombus and reduction of portal venous blood flow, and that massive hepatic necrosis may be induced by coexistence of endotoxin and marked reduction of portal venous blood flow.

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Injected vascular specimens corresponding to the identical histologic lesion in 63 autopsy cases of hepatic cirrhosis were made and observed.
In fine granular cirrhosis whose nodules were less than 3mm in diameter, the main vascular lesions were observed in the central veins and the nodules were surrounded by the fibrous connections which linked mainly the adjacent central veins.
On the other hand, in nodular cirrhosis whose nodules were ranging over 3mm in diameter, the main vascular lesions were observed in the portal veins less than 50-100μm in diameter and the nodules were formed between portal veins 100-200μm in diameter.
These characteristic findings led to the conclusion that the size of nodules was dependent upon the location of derangement in the intrahepatic vasculature and one type of cirrhosis was unlikely to be transformed into the other type.

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The fibrosis of Glisson's sheaths of idiopathic portal hypertension (IPH) includes asteroid and round types. The asteroid type fibrosis was thought to be derived from chronic hepatitis and the round type fibrosis was from chronic cholangitis.
In the present investigation we have studied morphogenesis of round type fibrosis utilizing wedgebiopsied livers of 96 patients of IPH. There were 15 cases with round type fibrosis. Among them 3 cases had lymph follicles in the Glisson's sheaths and 9 cases revealed an intermediate type fibrosis between asteroid and round type fibrosis. One of these 8 cases had lymph follicles in Glisson's sheaths. It seems that lymph follicles enlarged Glisson's sheaths in a round shape resulting in fibrosis of periportal area followed by concentric fibrosis with replacement of lymph follicles. Chronic cholangitis was not recognized in any cases of round type fibrosis. Therefore, it may be concluded that round type fibrosis is derived not from chronic cholangitis but from chronic hepatitis and IPH is essentially as the same as chronic hepatitis in origin.

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Five tumor markers, which tend to increase in the patients' sera in an association with hepatocellular carcinoma (HCC), were studied by means of immunofluorescent technique in the tissues from 20 bearers, and albumin in some cases. Alpha-fetoprotein (AFP) and carcino-embryonic antigen (CEA) were detected in tumor cells in frequency of 80% and 55% of total cases respectively. Ferritin (Fr), β2-microglobulin (β2-m) and human chorionic gonadotropin-subunit (βhCG) were less common. Positive frequencies of these markers were parallel with their appearances in the sera of HCC. Regarding the relationship between these tumor markers and differentiation of tumor cells, it was concluded that these antigens were mainly expressed in the well-differentiated type based upon Edmondson's criteria. In 14 cases (70%), at least 2 antigens, most frequently AFP and CEA were detected at the same time. From this study, it is suggested that HCC is functionally heterogenous in spite of monomorphic appearance, and also an introduction of new tumor marker which is existent in HCC without any relationship with differentiation or expressed dominantly in poor differentiated type should be searched for an improvement of early detection of HCC.

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Human hepatoma cells serially transplanted in nude mice, HC-4, 20, 28, 32, were investigated for maintaining in vitro. Only one cell line, c-Hc-4, has been established and maintained for more than 5 years. The hepatoma originated in 45 year-old man with liver cirrhosis.
The cell grew in vitro forming a sheet of monolayered cells and firmly attaching to the inner surface of cultured flasks. Morphologically they showed epithelial-like pattern. The doubling time was about 20 hours. Their modal chromosome number was 58. Serial heterologous transplantation in nude mice was successful. The histological finding was almost the same patterns as those in the primary tumor.
The cultured cell line produced alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA).
The subclones of c-Hc-4 cells produced various amounts of AFP and CEA. The high CEA producing subclone grew more rapidly than the AFP producing and AFP-CEA none-producing clones. C-Hc-4 cell line seemed to be useful for studies on hepatic oncology.

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In 10 patients with hepatocellular carcinoma, hepatic arterial embolization was performed under laparotomy (Surgical embolization). In 6 of 10 patients, main part of the tumor was resected leaving lesions partially in the liver. For the therapy of the remnant lesions, embolization was performed. The other 4 cases were nonresectable where transcatheter arterial embolization was unsuccessful.
After the operation serum GOT, GPT and LDH levels increased temporarily, recovering to preoperative values in ca. 10 days. The tumor stain of the remnant lesion disappeared completely in angiography except 1 case, showing good effect on the tumor tissue, together with marked decrease in density of the tumor tissue and diminished low density areas in computed tomography.
Surgical embolization seems useful not only as treatment of nonresectable cases, but also as adjuvant therapy in resectable cases, such as with a part of lesion remaining in the liver.

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132 patients with hepatoma complicating liver cirrhosis were subjected to the transcatheter arterial embolization (TAE). Gelfoam sponge was used as embolic material. The embolic effects were evaluated by means of computed tomography, follow-up angiography and serum AFP level.
As a results, the tumor was reduced in size and the attenuation coefficients of the tumor in CT was decreased (10-20HU) suggesting the ischemic necrosis of the tumor cells.
Serum AFP level was decreased remarkably after TAE. The degree of the tumor necrosis was well correlated with the exsistence of the tumor capsule and the degree of vascularity in angiographic findings, The prognosis was mainly depended on the size of tumor, complicated liver cirrhosis and the degree of portal obstruction by tumor invasion into the portal vein. One year survival rate was 43.5% and two years was 30.3%.

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A 36-year-old female was admitted with chief complaints of jaundice and pruritus. She had a history of taking Tiopronin (total dose: 8100mg) for skin disease. Serum levels of GOT (332 U/l), GPT (645 U/l), total bilirubin (11.4mg/dl) and Al-P (378 U/l) were elevated when she was admitted. The diagnosis of Tiopronin-induced liver injury was confirmed by a positive lymphocyte stimulation test With Tiopronin. A needle biopsy specimen of the liver revealed obvious degeneration and destruction of the interlobular bile ducts. The bile duct lesions persisted even at the time of re-biopsy 6 weeks after the first biopsy. It is important to recognize from this case that Tiopronin can induce marked degeneration and destruction of the interlobular bile ducts which clearly mimic the pathologic lesions of primary biliary cirrhosis. Persistence of the degeneration for 6 weeks or longer must be kept in mind when Tiopronin is prescribed

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A case of intrahepatic cholestasis successfully treated with plasma exchange was reported. A 46-year-old male patient was admitted to our hospital because of general malaise and severe jaundice. Total serum bilirubin increased by 27.4mg/dl, though his transaminase levels decreased after admission. He received treatment including prednisolone and glucagon-insulin with no beneficial effect. The plasma exchange with fresh frozen plasma, therefore, was performed by using IBM 2997 blood cell separator on the 28th and 30th hospital days, which resulted in remarkably improving his jaundice.
From this result, plasma exchange was useful treatment for intrahepatic cholestasis, and the mechanism by which plasma exchange favours hyperbilirubinemia was discussed.

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A 46-year-old alcoholic man with complaints of common cold like symptom and abnormal behavior was admitted to this department. Various investigations indicated advanced liver cirrhosis. Real-time ultrasound in the right intercostal section demonstrated a large conduit continuous from the portal vein to the inferior vena cava through, and behind the liver. Computed tomography revealed a sausageshaped low density channel connecting hepatic hilum and inferior vena cava, and bolus injection contrast enhancement demonstrated transit of contrast medium from the portal vein directly into the inferior vena cava through the sausage-shaped low density channel. Superior mesenteric arteriography demonstrated varicose veins in the hilar regions of the liver in the venous phase.
The catheter introduced into the inferior vena cava for hepatic vein catheterization showed large opening of this portal vena caval shunt.
Measurements of ammonia level and PaO₂ at various levels of the inferior vena cava during the catheterization clearly indicated that portal vein blood was being shunted through this channel.

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A 26 year-old man was admitted to our hospital because of a right hypochondralgia and a high fever, A diagnosis of congenital cystic dilatation of intrahepatic bile ducts (Caroli's disease) was made. Although the patient underwent a right lobectomy of the liver, he died 3 months after the operation. The surgically resected liver and the autopsied liver were investigated and compared in details.
Microscopically, hyperplastic epithelium of the cystic dilated bile ducts and proliferated, bizarre bile ducts in the portal areas with moderate fibrosis and slight inflammatory change were observed. Renal tubular ectasia was also observed in the bilateral kidneys.
In this paper, we discussed the relationship between Caroli's disease, congenital hepatic fibrosis and choledochal cyst, and reviewed 35 cases reported in the literature.

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