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ABSTRACT: Fulminant hepatitis is associated with apoptosis of hepatocytes, which is mediated via Fas and tumor necrosis factor (TNF) receptors. The clinical significance of apoptotic factors and these receptors was investigated in fulminant hepatitis.
Serum levels of TNF-alpha, soluble TNF receptor-I and -II, soluble Fas antigen, and Fas ligand were measured. Then, the relationships between these parameters and the severity or prognosis of fulminant hepatitis were studied.
Serum levels of TNF-alpha, soluble TNF receptor-I, and soluble TNF receptor-II were increased in acute-type fulminant hepatitis. In particular, soluble TNF receptor-I was significantly higher than in patients with subacute-type fulminant hepatitis, severe acute hepatitis, acute hepatitis, or healthy controls. The soluble TNF receptor-I level continued to increase or remained high in patients who died of acute-type fulminant hepatitis, and eight of nine patients had a level >10 ng/ml. In contrast, the soluble TNF receptor-I level remained <10 ng/ml in survivors. Soluble Fas and soluble Fas ligand levels tended to increase in all types of acute liver disease and were not specific to fulminant hepatitis.
Our findings suggested that monitoring the soluble TNF receptor-I level may help to assess the prognosis of acute-type fulminant hepatitis and that TNF might be associated with massive hepatic necrosis.
The American Journal of Gastroenterology 08/2000; 95(8):2040-6. · 7.28 Impact Factor
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ABSTRACT: The aetiology of idiopathic portal hypertension (IPH) is unknown. However, some evidence of immunological abnormalities in IPH patients has been reported.
As adhesion molecules are important in the interaction between lymphocytes and accessory and target cells, the expression and release of the soluble form of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule (ICAM-1) were examined in this study.
In IPH patients, the serum level of soluble VCAM-1 was found to be increased, compared with that of healthy subjects, fatty liver patients and chronic hepatitis patients. The level of soluble ICAM-1 of IPH patients was found to be slightly increased, compared with that of healthy subjects; however, it was not different from the level in patients with other diseases. The expression of VCAM-1 was observed in the sinusoidal lining cells and endothelial cells around the liver vessels of several IPH patients. In contrast, ICAM-1 was weakly expressed in sinusoidal lining cells and hepatocytes in the liver tissue of only one of four IPH patients.
This differential pattern of VCAM-1 and ICAM-1 was found in IPH patients and it was suggested that VCAM-1 might be an important molecule in the occurrence of IPH.
Journal of Gastroenterology and Hepatology 05/1999; 14(4):364-9. · 2.87 Impact Factor
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ABSTRACT: Human fulminant hepatitis tends to be classified into two groups: acute type (A-FH) and subacute type (S-FH). In order to define these two clinical entities more precisely, we examined and compared peripheral blood lymphocyte subsets in A-FH and S-FH patients. We found that S-FH patients had a higher prevalence of CD19+ B cells (31.1 +/- 7.6% in S-FH vs 12.7 +/- 3.7% in A-FH) and also a lower prevalence of CD3+T cells (50.2 +/- 8.7% in S-FH vs 65.6 +/- 10.5% in A-FH). Furthermore, by examining the absolute cell numbers of these subsets, we determined that their imbalance in S-FH was mainly due to a decrease in CD3+ T cells. Among several T cell subsets, the CD8+CD11b-T cell subset was elevated in A-FH and decreased in S-FH (6.1 +/- 2.1% in S-FH, 24.4 +/- 5.8% in A-FH, and 14.8 +/- 7.8% in control). Serial studies of two S-FH patients revealed that the imbalance of these lymphocyte subsets returned to their proper ratio together with the improvement of their liver injury. These results indicate that there might be a different immunological background between A-FH and S-FH.
Journal of Gastroenterology and Hepatology 04/1999; 14(3):274-80. · 2.87 Impact Factor
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ABSTRACT: The humoral immune response to acute infection by hepatitis C virus (HCV) is not yet perfectly clear in terms of immunoglobulin (Ig) response, diversity of HCV antigen, and the relation with hepatitis severity and antibody response. Serum IgM and IgG anti-HCV levels in patients with HCV and either acute hepatitis (AH) or fulminant hepatitis (FH) were investigated; the diversity of HCV antigen was investigated by RIBA test III. Of 22 AH patients, 12 (54.5%) were positive for IgM anti-HCV, mainly reacting to HCV core protein. The mean interval until the appearance of IgM anti-HCV after onset was 24.1+/-26.2 days. IgG anti-HCV mainly reacted to both core and NS-3 antigen, appearing 42.6+/-42.1 days after onset. From a serial study of 15 AH patients, it was considered that in seven AH patients (46. 7%), the IgM response would precede the IgG response. In another two AH patients, IgM anti-HCV was not detected during the acute disease phase. Of 48 chronic hepatitis patients with HCV-RNA, 40 patients were positive for IgM anti-HCV. Therefore, IgM anti-HCV was useful for diagnosis in some of the AH patients, but it was difficult to use for distinguishing between acute and chronic infection. All four FH patients with HCV-RNA were positive for both IgM and IgG antibody to HCV at onset. Their antibody titres were higher than those of AH patients. These results suggested that, as in FH due to HBV, FH due to HCV could induce strong and rapid humoral immunity.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 14(7):593-8. · 1.21 Impact Factor
