We examined the proliferative responses of peripheral blood mononuclear cells (PBMC) to recombinant HBsAg, PreS₂+SAg and HBcAg from patients with acute hepatitis B (AH) (n=14), chronic hepatitis B (CH) (n=29), asymptomatic hepatitis B virus carrier (ASC) (n=19) and controls (n=9). The responses to both r-HBsAg and PreS₂+SAg showed low levels in patients with AH, CH and HBeAg-positive ASC, while the responses in HBeAb-positive ASC were sligtly higher than those in controls. As to r-HBcAg, strong T cell proliferation was noted in most of patients with AH during acute phase of illness, but these response became decresed and undetectable in recovery phase. In chronic hepatitis B patients, the response to r-HBcAg remained low except several HBeAg-positive cases who had IgM anti-HBc in sera or were before acute exacerbation. Thus, T cell sensitization to HBcAg may exsist in the reactivation of chronic HBV infection. However, inadequate T cell responses to HBV antigens may be more important in the persistance of HBV infection.

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Peripheral and intrahepatic lymphocyte subsets were analyzed in 22 patients with chronic hepatitis by two-color flow cytometry. Activated T cells in the liver had significantly increased compared with those in the peripheral blood. There were significantly more activated T cells in the livers of the patients whose ALT levels were more than 200U/L than in those whose ALT levels were less than 200U/L during the one month before liver biopsy. Helper T cells had increased, but the CD4⁺cells had decreased due to a marked decrease of suppressor inducer T cells. CD8⁺ cells had increased due to a increase of both cytotoxic and suppressor T cells. Fc receptor positive cells, which had increased significantly, were not NK cells but Fc receptor-bearing T cells. In comparison with ordinary immunohistochemical methods, flow cytometric analysis enables more objective quantitation and simpler two-color staining of intrahepatic lymphocyte subsets.

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Liposome-encapsulated human recombinant Cu-Zn superoxide dismutase (LSOD) pratected acetaminophen (APAP)-induced liver cell necrosis, whereas liposome, free superoxide dismutase or heat denatured SOD encapsulated into liposome had no such an effect in Sprague-Dawley rats. LSOD did not alter the metabolism of APAP as assessed by either the extent of the covalent binding of APAP metabolites to hepatic macromolecules or by the depletion of hepatic reduced gultathione but completely abolished the induction of hepatic lipid peroxidation by APAP.
The present results demonstrate a participation of an acute oxidative stress in the mechanism of the induction of the liver cell necrosis by APAP.

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The effect of OK-432 on Kupffer cell function, production of interleukin 1 (IL-1) and tumor necrosis factor (TNF), was examined. OK-432 enhanced IL-1 production by Kupffer cells stimulated with or without lipopolysaccharide (LPS), and promoted TNF synthesis by Kupffer cells stimulated with LPS. On the other hands, Kupffer cells which obtained from mouse injected with OK-432 increaed in number and produced both IL-1 and TNF more than those from normal mouse. These results suggested that OK-432 activates Kupffer clles both in vitro and in vivo, and modulate local immunological reactions in the liver.

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Eleven patients with acute hepatic failure were studied. Plasma exchange (PE) was performed fifty times on those patients. Approximately 3000ml of fresh frozen plasma (FFP) was used as replacement fluids. Arteril blood was taken at start of PE. One hour and 24 hours after PE. Acetoacetate (ACAC), β-hydroxybutyrate (BOHB), pyruvate and lactate were measured and then ketone body ratio (KBR=ACAC/BOHB) and pyruvte/lactate (P/L) were calculated. KBR and P/L of FFP were also measured. PE did not change the values of KBR and P/L significantly. Therefore it is likely that PE did not appear to affect redox status of the heptocytes. However, considering that ACAC, BOHB and KBR of FFP was significantly lower than those of arterial blood and that approximately 3000ml of FFP was replaced, PE caused remarkable change in metabolism of ACAC, BOHB and subsequently that of KBR. In addition, theoretical values of ACAC and BOHB in artrial blood, which were calculated by the equation of one pool modle, were significantly higher than actual values. These facts suggest that PE improved metabolism in ACAC and BOHB, especially in ACAC, leading to improved KBR.

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Systemic and hepatic hemodynamics in the experimental liver cirrhosis induced by thioacetamide treatment were evaluated using radioactive microsphere method. The histology of the rats was compatible with liver cirrhosis in human. In the cirrhotic rats, portal pressure and portal systemic shunting significantly increased compared with the controls. The increase of the portal venous inflow resulted from the systemic and splanchnic hyperdynamic circulation and the elevation of the portal venous resistance was observed in cirrhotic rats. These phenomena result in portal hypertension in the cirrhotic rats. Effective hepatic blood flow was decreased in the cirrhotic rats in spite of the increase of the portal venous inflow.
The thiocetamide induced cirrhotic rats showed a similar pathogenesis in the portal hypertension in the cirrhosis in human. Therefore, this model might be suitable for the study of the hemodynamics in the portal hypertension in cirrhosis.

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The livers of monosodium glutamate (MSG)-treated rats and normal control rats were investigated in vivo using ¹H- and ³¹P-magnetic resonance (MR) spectroscopy. The liver of MSG-treated rats showed a remarkable fatty change histologically and their triglyceride content was much greater than that in control rats. ¹H-MR spectra of MSG-treated rats showed an obvious fat peak in addition to a water peak. There was an excellent correlation between the peak area ratio of fat to fat plus water obtained from 1H-MR spectroscopy in vivo and triglyceride content in the liver specimens measured by a thinlayer-chromatography-flame-ionization (TLC-FID) metbod. ³¹P-MR spectra of both MSG-treated and control rats revealed 6 peaks, which were assigned to phosphomonoester (PME), inorganic phosphate (Pi), phosphodiester (PDE), γ-ATP, α-ATP, β-ATP. The peak height ratio of Pi to α-ATP was higher in MSG-treated rats than in control rats. The chemical shift of Pi relative to α-ATP was smaller in MSG-treated rats than in control rats, suggesting a slight acidosis in the liver of MSG-treated rats. These data demonstrated that ¹H- and ³¹P-MR spectroscopy were useful for evaluation of accumulation of fat and related metabolic derangements in fatty liver.

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We studied the natural course of 31 patients with asymptomatic primary biliary cirrhosis (a-PBC) and also evaluated clinicopathological effects of ursodeoxycholic acid (UDCA) treatment on 16 cases out of them. No significant change of serum ALP, γ-GTP, ALT or IgM level was observed in the period before UDCA treatment, and four cases became symptomatic after a mean period of 19.5 months. After 600mg/day of UDCA administration, we found a significant decrease in serum ALP, γ-GTP, ALT and IgM levels. Histopathological findings of liver specimens in each patient were graded in 6 categories: lymphocytic piecemeal necrosis, cholestasis, disappearance of bile duct, bile duct inflammation, fibrosis and portal inflammation. Only the score of bile duct inflammation fell in the pretreatment period, while a significant improvement in scores of cholestasis, bile duct inflammation, fibrosis and portal inflammation was observed after UDCA treatment. These results strongly suggest that UDCA treatment for a-PBC is very effective in both clinical and pathological aspects.

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Transcatheter hepatic segmental chemoembolization using Lipiodol mixed with an anticancer drug followed by te injection of gelfoam prticles which was introduced into the tumor-bearing hepatic segment as the target area (Segmental Lp-TAE) was carried out in 9 patients with hepatocellular carcinoma undergoing hepatectomy after Segmental Lp-TAE. Anti-tumor effect and influence on nontumor area were histopathologically studied in these cases. Complete necrosis of the tumor was attained in 7 of 9 cases. The degree of necrosis correlated with the degree of Lipiodol accumulation in the tumor and its vicinity. Necrosis of non-tumor area in the vicinity of the tumor was observed in part and this findings correlated with Lipiodol accumulation, however, there were no diffused sever changes inducing hepatic dysfunction. These results suggest that segmental Lp-TAE has anti-tumor effect comparable with that of hepatectomy and is an excellent treatment for hepatocellular carcinoma, rarely causing complications.

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If the amount of Lipiodol infused into th hepatic artery exceeds a certain level, Lipiodol flows into the portal vein. Utilizing this phenomenon, an anti-cancer agent, emulsified in Lipiodol, was infused via the haptic artery into the portal branch of the target segment, followed by Gelfoam injection to obstruct the segmental arterial branch. This segmental chemoembolization is called Cement therapy. Of the 4 cases of hepatocellular carcinoma in which heptectomy was performed after Cement therapy, all but one case (in which collateral supply was observed) showed complte necrosis of the main tumor and daughter nodules as well as infarction of the cancer-free region. In the follow-up of 41 cases of hepatocellular carcinoma after Cement therapy, CT revealed almost 100% retention of Lipiodol and hepatic scintigraphy discloed segmental uptake reduction. One- and two-year cumulative survival rates for these 41 cases were as high as 86.7% and 60.7%, respectively.

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A 43-year-old man was admitted for the post-transfusional hepatitis in 1978. Liver needle biopsy was performed in 1980 and diagnosed as chronic active hepatitis. During the course of illnes, he complained no symptoms. Serum IgM elevated from 199mg/dl (1980) to 1161mg/dl (1988) during a period of about 8 years. Because of the extremely high level of serum IgM, primary biliary cirrhosis (PBC) was suspected. The laboratory data showed no elevation of serum bilirubin, alkaline phosphatase and γ-GTP but antimitochondrial antibody was always positive in 1988.
Therefore, laparoscopic examination was perfomed and diagnosed as PBC stage I according to the Scheuer's classification in 1988. The first liver biopsy specimen were reexamined and there were the findings of PBC in addition to that of chronic hepatitis.
The increase of serum IgM in the clinical course of PBC was observed in this case and it was suggested that pathological abnormality may preceede the biochemical abnormality such as elevation of IgM, alkaline phosphatase and γ-GTP in PBC.

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At autopsy, a case of peliosis hepatis was found incidentally in a patient receiving diethylstilbestrol for seven years for prostate cancer. We stueied a direct correlation between ultrasonography (US) and histology of peliosis hepatis using the formalin-fixed autopsied liver.
The US of peliosis hepatis was not hyperechoic image, but iso- and hypoechoic heterogeneous echo texture. Histologically, peliosis hepatis was multiple small cystic blood-filled spaces without endothelial lining. Communication of the cystic spaces with sinusoids were evident. These histological architectures were different from cavernous hemangioma, which shows hyperechoic image. Main cause of non-hyperechoic image of peliosis hepatis may be due to above described histological architectures.

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A 64-year-old woman was referred to our hospital for further examination of a liver mass which was identified with ultrasound. Liver function tests revealed normal, and tumor markers were negative. Ultrasound disclosed a hyperechoic lesion with hypoechoic area and tubular structures inside, along with irregular and obscure contour in the posterior segment of the liver. The lesion was demonstrated as a low density area on computed tomographic scan, which was not enhanced with contrast medium. On angiography and CT arteriography of the liver, the posterior inferior branch of the hepatic artery was enlarged and tortuous. There was prominent hypervascularity around the central hypovascular lesion. Moreover, early filling of hepatic veins and mottled capillary blush throughout the right lobe of the liver were noted. From these findings, we made a diagnosis of hepatic arteriovenous malformation based on hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber's disease. Our case has very unique findings on imaging study, compared with previous reports of hepatic arteriovenous malformation.

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We reported a rare case of Alagille syndrome with partial nodular transformation. In January 1988, a 30 years-old man was admitted to our hospital to work up for liver injury. US, CT and MR-CT revealed a nodule containing vessels, 11×6cm in size, in the right anterior and left medial segments of the liver. ^99mTc-HIDA scintigram of the liver after 45min revealed that the biliary tree was not seen in the surrounding area of the nodule inspite of visualization of the common bile duct. We performed a right anterior segmentectomy, because the nodule compressed the main truncus of portal vein. In macroscopic finding the nodule, 11×6×8cm in size, 450g in weight, did not have capsule and compressed the surrounding hepatocytes. In microscopic findings, the nodule contained portal tracts and hepatocytes revealed hyperplasia, on the other hand, in the surrounding liver tissue P-P and P-C bridiging were seen and there were many collateral vesseis and bile duct structure were not seen. From these pathological and clinical observation with characteristic face and esophageal varices, we diagnosed this case Alagille syndrome with partial nodular transformation. We suspected the pathogenesis of the hyperplasia with ductal hypoplasia in this case was uneven perfuison of the intrahepatic portal venous blood flow.

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A case of liver cyst considered as a rare complication of clonorchiasis was reported. A 81 year-old man was admitted because of right hypochondralgia. A unilocular large cyst was discovered in the right lobe of the liver. Communication existed between the irregularly dilated intrahepatic bile ducts and the cyst on ERCP. Ova of Clonorchis were discovered in the aspirated cyst fluid. Biopsy specimen from the cyst wall demonstrated inflammatory reaction. Oral administration of Praziquantel was effective; number of ova in the cyst fluid and in the feces decreased nearly to zero. The cyst decreased in size after medication, finally disappeared at one year of follow-up. As far as we know, this is a first reported case of clonorchiasis complicated by liver cyst.

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