We studied the clinical significance of the binding activity to polymerized human serum albumin (pHSA-BA) and pre-S antigen (pre-S Ag) as predicting markers of prognosis in patients with chronic hepatitis B (CHB) with antiviral tratment. The pHSA-BA and pre-S Ag were measured using enzyme immunoassay and their values were expressed as optical density at 492nm (negative<0.5). There was a good correlation between pHSA-BA and pre-S Ag titers with r=0.961. The levels of pHSA-BA and pre-S Ag decreased under 0.5 in 8 patients (Group A) just after treatment, while in the remaining 20 patients (Group B), these levels were persistently over 0.5 after treatment. Five patients (62%) in Group A had persistently normal alanine aminotransferase (ALT) levels during a follow-up period after treatment, while the remaining 3 had elevated ALT levels with elevation of pHSA-BA and pre-S Ag levels after treatment. Two of the these 5 patients were positive for HBeAg. Seventeen patients (85%) in Group B had elevated ALT levels, with 2 being negative for HBeAg and 3 positive for anti HBe. These results indicate that pHSA-BA and pre-S Ag may be useful markers in predicting the long-term prognosis of CHB patients with antiviral treatment.

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To clarify the differences in nutritional background of the patients with alcoholic liver diseases between U.S.A. and Japan, 60 Japanese alcoholic patients (9: alcoholic hepatitis, 51: alcoholic liver cirrhosis) were studied in comparison with 40 American alcoholic patients (21: alcoholic hepatitis, 19: alcoholic liver cirrhosis). Alcohol contributed about 50% of total calorie intake in both countries. American patients with alcoholic hepatitis or alcoholic liver cirrhosis had higher fat intake than Japanese patients (U.S.A. 20Cal%, Japan 10Cal% p<0.001). Protein intake was 7-9% of total calorie intake of American and Japanese patients. Laboratory data such as serum levels of total bilirubin and albumih showed more abnormal values in American patients than in Japanese.
These results suggest that dietary fat may be involved in the clinical differences in the severity of alcoholic liver disease, which exists between American and Japanese patients.

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The principle of polymerase chain reaction (PCR) is to amplify the DNA exponentially by repeating the polymerase reaction. We detected the HBV DNA in serum specimens applying PCR method. For determination of the sensitivity of this method, serially diluted HBV DNA (1-10^-7pg) were examined.Cloned HBV DNA equivalent to one virus genome (10^-6pg) was detectable by ethidium bromide staining after 50cycles of PCR. The amplified DNA with PCR was proven to have the homology with HBV DNA by Southern blot. In serum specimens, HBV DNA was detected in 5 of 5 HBeAg seropositive, in 2 of 2HBe Ag/Ab seronegative, in 8 of 10HBeAb seropositive, but in none of 6 HBsAg seronegative cases. Small amount of HB virus seems to present in sera of many HBeAg seropositive patients.

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We investigated the distribution of portal blood flow per kilogram body weight (PBF/BW) in 112 healthy volunteers and 90 patients with liver cirrhosis using an ultrasonic Doppler duplex system. The PBF/BW in healthy volunteers showed a log-normal distribution, while the distribution was irregular and showed two peaks in patients with cirrhosis. This irregular distribution was thought to reflect the complex physiopathologic condition of patients with cirrhosis.
We analyzed the relationship between PBF/BW and the data from hepatic function tests (serum albumin, total bilirubin, ICG 15-min retention rate and ICG plasma disappearance rate) in 48 patients with liver cirrhosis. Patients were divided into four groups; group A with a hepatofugal or stagnant portal blood flow, group B with a hepatopetal PBF/BW of less than 12ml/min/kg, group C with a hepatopetal PBF/BW of 12 or more but less than 20ml/min/kg, and group D with a hepatopetal PBF/BW of 20ml/min/kg or more. Group A showed the worst results in hepatic function tests, group D the second worst, and group C the best. The effective heaptic blood flow (EHBF) was thought to have decreased because of the development of extrahepatic portasystemic shunts in the patients in group A, and EHBF to have decreased because of the development of intrahepatic shunts in patients in group D. The results of hepatic function tests deteriorated as a consequence of the decrease in EHBF.

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Detection of antimitochondrial antibody (AMA) is useful for diagnosis of primary biliary cirrhosis (PBC). Although immunofluorescent techniques are widely used for the detection of AMA, their sensitivity and specificity are not sufficient. We developed a dot-immunobinding assay for AMA using aspirating microplate. This assay method is as sensitive and specific as the immunoblot method. Using this dot-immunobinding method, we observed six patients who tested negetive results for AMA by immunofluorescent staining. The sera of all patients tested positive by the dot-immunobinding assay with varied titer. The clinical course could be followed in three cases and positive results for AMA continued during observation, even though immunofluorescent results became negative. These results suggest that the dot-immunobinding assay is a sensitive and specific technique detecting AMA in PBC.

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A study was conducted to investigate changes of tryptophan (Trp) transport across blood-brain barrier in hepatic encephalopathy. Hepatic failure was induced in rats by either portacaval anastomosis (PCA), acute ischemic hepatic failure (AIHF) or continuous infusion of ammonium acetate (NH₃). The permeability of blood-brain barrier to Trp was examined employing the method of brain uptake index (BUI). The following results were obtained:
1) PCA as well as AIHF rats showed significantly higher BUI of ¹⁴C-Trp as compared with control.
2) In NH3-infused rats, significant elevation in BUIs of ¹⁴C-Trp and of ¹⁴C-isoleucine was observed when compared to control.
3) In all of three hepatic failure models, a significant positive correlation was demonstrated between BUI of ¹⁴C-Trp and glutamine levels in the brain, which is elevated presumably due to the enhanced detoxication of NH₃ in the brain.
In conclusion, the increased permeability of blood-brain barrier in hepatic failure is clearly demonstrated and is further suggested to have been induced by elevated cerebral level of glutamine. In addition, it is also conceivable that the increased permeability of blood-brain barrier may contribute to the elevation in cerebral concentration of neutral amino acids such as Trp.

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Measurement of NK activity was made by ⁵¹Cr-releasing assay using K562 cells. NK activity was preserved in patients with liver cirrhosis (LC) but decreased in patients with hepatocellular carcinoma (HCC).
Measurement of NK activity in phenotype was made by negative selection method mainly based on the method of Perussia et al., using Leu7, CD16, CD11 and CD8 as monoclonal antibody. NK activity with Leu7-positive cells showed increase in LC but decrease in HCC. NK activity with CD16-positive cells showed no decrease in LC but decrease in HCC. NK activity with CD11-positive cells showed remarkable decrease in both LC and HCC, while NK activity with CD8-positive cells showed no decrease.
Analysis of surface markers of NK cells by two color flowcytometry method was done. Leu7-CD16⁺ cells were decreased in LC and HCC, Leu7⁺CD16⁺ cells were maintained in LC but remakably decreased in HCC, whereas Leu7⁺CD16^- cells were preserved in LC but slightly increased in HCC.
These data suggest that phenotypical changes of NK cells are due to the maturation arrest of NK cells in LC and HCC, resulting in changes of NK activity in these diseases.

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Extracted human liver tissues were examined by immunoelectron microscopy to study the heterogeneity of intermediate filaments of hepatocytes. Frozen sections of liver tissues were extracted by Triton X-100 and nucleases. Immunoelectron microscopy was performed by using MA-902 (CK No. 8), RPN. 1160 (CK No. 18) and CAM5.2 (CK No. 8, 18 & 19). Transmission electron microscopy showed that the cell borders were well defined by meshworks of numerous IFs and the pericanalicular sheaths composed of IFs were identified as tube-like structures. A meshwork of IFs was seen in the cytoplasm. The diameter of each IF was around 10nm. Immunoelectron microscopy showed that IFs appeared to be strongly stained with antibody MA-902 or CAM5.2 compared with antibody RPN. 1160. Double label immunoelectron microscopy showed that some bundles of filaments were stained with both antibody MA-902 and RPN. 1160. These results suggested that IFs without staining by CK No. 18 were seen in normal human hepatocytes and some of the IFs were shown to contain both cytokeratin polypeptides in a single filament.

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Dynamic CT was performed on 11 healthy control (N), 30 cases of fatty liver (FL), 21 cases of chronic hepatitis (CH) and 47 cases of liver cirrhosis (LC) using 0.4mg/kg of 65% meglumine diatrizoate. Eleven scan were taken in 207 seconds and CT numbers of the ROI were measured to get time-density curve (TDC). The curve for a single pass of the media was obtained by the analysis of TDC, using gamma variate function and least square method. PT (peak time), DT (decay time) and M1 (first moment) were calculated. PT, DT and M1 of right lobes were in the order of N<FL=CH<LC. In N, PT and M1 were larger in left than right lobe, while in FL and LC, they were larger in right than left. There were significant correlations between PT, DT or M1 of right lobe and ICG R₁₅, serum albumin, choline esterase, γ-globulin and hepaplastin test. Principal component analysis showed that combination of PT, DT, M1 and the liver tests were useful to get more accurate differential diagnosis of these diseases than the liver tests were used independently.

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We experienced siblings who were born to an anti-HBe positive HBV carrier mother and suffered from chronic liver dysfunction. The senior sister developed severe hepatitis type B at two month of age. But moderate liver dysfunction persisted for 12 months after positive conversion of HBs antibody. It was suggested that she had been transmitted HBV and Non-A, Non-B hepatitis virus (NANBV) concomitantly at birth. Her junior brother was administrated hepatitis B hyper-immunoglobulin just after birth to block of mother-to-infant transmission of HBV. But he also suffered from chronic liver dysfunction after two months for 11 months. HBs antibody elevated and HBc antibody reelevated spontaneously from 8 months after birth. It may also be possible that NANBV prolonged the incubation time of HBV.

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We report a case of disappearance of non-suppurative cholangitis and decrease of antimitochondrial antibody levels observed by three histological examinations of the liver. The patient was a forty-year-old female. She had no particular past history. She was admitted with common-cold like symptoms and jaundice. The finding of a positive AMA (320×) suggested the possibility of primary biliary cirrhosis (PBC), but by the clinical course and histological findings she was diagnosed as having acute cholestastic hepatitis and discharged. After 3 month's observation, elevation of hepatobiliary enzymes was observed again, and liver biopsy was done. Histologically, it showed typical PBC. Six months later, colloid reaction and hepatobiliary enzymes changed to normal. Two years and three months after the first examination, PBC was not seen histologically. There was no clinical symptoms and all laboratory studies were normal except for an IgM level of 267mg/dl and a positive AMA (80×). It was thought that there was a possibility of it being a case of asymptomatic PBC complicated by acute hepatitis, and as a result due to some type of immunological mechanism.

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A 49-year-old man was admitted to the hospital because of liver dysfunction and multiple hyperechoic lesions in the liver. He has the history of blood transfusion and diabetes mellitus, for which he takes Glibenclamide. For 30 years he had drunk one bottle of beer per day. There was no family history of skin disease. On admission, there was no pigmentation on the skin and no hepatosplenomegaly.
On peritoneoscopic examination, multiple dark purple colorations were found on the uneven liver surface. On ultrasonic peritoneoscopy, those lesions were described as hyperechoic lesions.
The aimed biopsy specimen of the dark purple lesion showed a weak red fluorescence under ultraviolet light.
Histology of the liver biopsy showed chronic persistent hepatitis, and fatty degeneration was observed in the dark purple lesion.
Since the examinations of porphyrins showed the increased contents of uroporphyrin and 7-carboxyl porphyrin in urine, the case was diagnosed as porphyria cutanea tarda.
Ultrasonic peritoneoscopy and peritoneoscopic ultrasonogram guided biopsy were the important diagnostic procedures for this patient.

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A 60-year-old man complaining of sudden epigastralgia followed by jaundice was admitted to Osaka Kousei-nenkin Hospital. A percutaneous transhepatic cholangiogram showed long tapered stricture of the extrahepatic bile duct. An abdominal angiography revealed severe stenosis of the portal vein at the porta hepatis. We diagnosed a cholangiocarcinoma and performed biliry decompression by internal drainage and chemotherapy. One year later, as the patient was in fair condition whose biliary stenotic lesion was not developed and stenosis of the portal vein was disappeared, the patient underwent a laparotomy. Pathological examination showed a diffuse non-Hodgkin's lymphoma, medium sized cell type arising from extrahepatic bile duct. Primary m alignant lymphoma of extrahepatic bile duct is very rate; there is a report of well-documented case by Nguyen and this case is the first report in Japan.

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Hepatocellular carcinoma (HCC), growing into an bile duct is rare. We present the recurrent HCC growing into the commmon bile duct like polyp with obstructive jaundice and hemobilia. Histopathologically, it was daiagnosed the mixed type of HCC and CCC, which Allen advocated.
A 53-years man, who presented a clinical picture of obstructive jaundice with upper abdominal pain, was found to have hepatoma and embolus blocking the common hepatic duct. Subsegmentectomy of the liver segment S7 and removal of the clot in the common hepatic duct were performed. Three months later, jaundice and spiky fever were found and the patient died of hepatic failure. At autopsy, recurrent hepatoma and tumor in the common bile duct growing like polyp were found and histopathologically, the recurrent tumor was diagnosed the mixed type hepatoma.

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