To clarify the contribution of HCV infection to the pathogenesis of autoimmune hepatitis (AIH), clinical findings and genetic background were compared between 31 cases of HCV marker-positive (C-AIH) and-negative chronic active hepatitis (P-AIH) who satisfied the diagnostic criteria for AIH. The onset of P-AIH was more than 10 years younger than that of C-AIH. The maximum transaminase levels and the titer of anti-nucleotic antibody of P-AIH were higher than those of C-AIH. The frequencies of DR4 and A24-B35-DR4-DQ4 haplotype of P-AIH were significantly higher in P-AIH group than normal controls (100% vs. 40.6%, 20.0% vs. 0.6%, respectively). The frequencies of B35 and B35-DR4-DQ4 haplotype of C-AIH were significantly higher than control (43.8% vs. 10.6%, 12.5% vs. 0.6%, respectively). The positive rate of DR4 between P-AIH and C-AIH was statistically different, however, there was no statistical significance between C-AIH and normal controls. These results suggested that HCV-related marker positive AIH (C-AIH) had different genetic background and clinical features from HCV-related marker negative AIH (P-AIH) which was diagnosed as prototype AIH.

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In patients diagnosed as having non-A, non-B liver disease (AVH: 24, CAVH: 93, cirrhotic stage: 7) based on liver histology, serum antibody titers were measured by theJCC. 2 ELISA kit derived from the core structure, KCL-163 and C-100 kit, and the relation between pathological activity and lymphocyte infiltration in portal area to JCC. 2 antibody levels were compared using the liver histology index score. KCL-163 and C-100 antibodies were detected in the 70-90% of patients with CAVH. The JCC.2 antibody positive rate was obviously high, and in about half with AVH. The JCC.2 antibody titer tended to be high in patients with severe inflammatory reactions. Lymph follicles were observed in about half with CAVH. But JCC. 2 antibody titer was not related to lymphocyte infiltration score, they did suggest that JCC. 2 antibody is more closely related to inflammatory reactions and HCV replication.

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Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease. In order to elucidate the role of urosodeoxycholic acid (UDCA) treatment through immune reaction, we studied lymphocyte function of patients with primary biliary cirrhosis with or without UDCA treatment. 28 patients with asymptomatic PBC (21 treated and 7 non-treated with UDCA (600mg/day, p.o.)) and 7 normal subjects were studied. 5 patients were evaluated before and after treatment with UDCA. In T cell subsets, the ratio of CD3 positive cell was low in patients treated with UDCA compared to that in patients without UDCA treatment (p<0.05). Although no significant difference among three groups was shown in the lymphocyte stimulation tests, the natural killer cell activity was significantly high and the interleukin 2 production was significantly low in patients treated with UDCA compared with those in patients without UDCA treatment (p<0.05). In vitro study, the natural killer cell activity became significantly low when peripheral blood mononuclear cells (PBMCs) were incubated with 1.0, 00.0 or 100.0μM of chenodeoxycholic acid (CDCA). However, the effect of CDCA on the natural killer cell activity was diminished when PBMCs were incubated with UDCA simultaneously. Thus, these data suggest that the effect of UDCA treatment for patients with PBC may be mediated through immune reaction induced by the change of bile acid composition.

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This study is undertaken to elucidate the efficacy of angiotensin II (AT-II) in high-dose intraarterial infusion of adriamycin (ADR) using direct hemoperfusion under hepatic venous isolation (HVI·DHP). Firstly, AT-II (3μg/kg) and ADR (3 mg/kg) were simultaneously given to mongrel dogs through the hepatic artery for 5 minutes under HVI-DHP. The adsorption rates (1-drug level at outlet of DHP/drug level at inlet of DHP×100%) of ADR and AT-II during HIV-DHP were determined. In addition, the effect of AT-II on the mean aortic pressure (MAP) and the abdominal aortic blood flow (ABF) were compared between animals treated with or without HVI·DHP. Secondly, using a rabbit model bearing VX2 tumor, we investigated the effect of AT-II on the tumor/nontumor (T/N) ratio of tissue ADR level. Two weeks after inoculation of VX2 tumor to the liver, animals received either ADR (n=5) or ADR plus AT-II (n=5) through the hepatic artery at the same dosages as described above under HVI·DHP, and were sacrified for measurements of tissue ADR levels. In animals treated with HVI·DHP, the adsorption rates of ADR and AT-II were maintained at levels as high as 90%, and MAP and ABF remained unaltered. On the other hand, in animals without HVI·DHP, MAP and ABF showed significant changes after AT-II infusion (p<0.01), thevalues at three minutes being 156% and 54%, respectively. The mean T/N ratio in the presence and the absence of AT-II were 0.17 and 1.95, respectively, demonstrating a significant increase in animals receiving AT-II under HVI·DHP (p<0.005). These results indicate that concomitant use of AT-II during high-dose chemotherapy under HVI·DHP may be of particular value to increase drug delivery to the tumor without affecting cardiovascular system.

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The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in patients with acute hepatic failure and in a rat model of hepatic encephalopathy. Endogenous benzodiazepine receptor ligands were extracted from serum by SEP-PAK C₁₈ column purification. Endogenous benzodiazepine ligands were assayed using both radioreceptor binding assays and enzyme immunoassays with anti-benzodiazepine antibodies. The severity of hepatic encephalopathy in patients with acute hepatic failure was not directly correlated with the level of benzodiazepine activity, and there was no significant difference in the mean value of plasma benzodiazepine activity between acute hepatic failure and controls, but five of eleven patients with acute hepatic failure and four of seven rats with experimental acute hepatic failure had obvious elevations of endogenous benzodiazepine receptor ligands. Although the source of endogenous benzodiazepine is still unknown, these results suggest that endogenous benzodiazepine may play a role in the pathogenesis of hepatic encephalopathy.

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To investigate the mechanism of elevated plasma endothelin-1 (ET-1) levels in patients with liver cirrhosis, ET-1 levels were measured both in inferior vena cava (IVC) and portal vein (PV) in rats carrying acute liver injury (AI) and liver fibrosis (LF) experimentally induced by CCl₄. There was a little difference in ET-1 levels between IVC and PV in LF, whereas ET-1 levels in IVC were significantly lower than those in PV in control. In AI, ET-1 levels of IVC and PV were both significantly elevated than those in control. The administration of prostaglandin E₁ derivative slightly elevated ET-1 levels in PV while it markedly lowered ET-1 levels in IVC. These results indicate that liver is the site of ET-1 degradation and the poor clearance of ET-1 is the reason of the elevation of plasma ET-1 levels in patients with liver cirrhosis.

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We report a case of minute peripheral cholangiocellular carcinoma (CCC).
A 47-year-old male was examined with a transient elevation of serum γ-GTP, as pointed out by mass screening. A small hyperechoic nodule with accoustic shadow was found in the liver on ultrasonography, but CT scan, angiography and MRI were unable to elicit a diagnosis. By ultrasoundguided fine-needle biopsy, we obtained a histological specimen of CCC, and an operation was performed. Resected specimen showed a peripheral CCC (11×9×9mm).

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