Elevated levels of 2′,5′-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during acute exacerbation of chronic hepatitis B

Shindo, Michiko; Okuno, Tadao; Arai, Ken; Matsumoto, Masayuki; Takeda, Makoto; Takino, Tatsuro; Sokawa, Yoshihiro

doi:10.1002/hep.1840090510

Hepatology

1989

DOI: 10.1002/hep.1840090510

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Elevated levels of 2′,5′-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during acute exacerbation of chronic hepatitis B

Michiko Shindo¹,

Tadao Okuno²,

Ken Arai³

et al.

Abstract: We measured 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum of 14 HBsAg- and HBeAg-positive patients with chronic hepatitis B with or without acute exacerbation. Elevated levels of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells and serum were found in seven chronic hepatitis B patients with acute exacerbation, whereas in the remaining seven chronic hepatitis B patients without acute exacerbation, both levels were similar to those of normal subject… Show more

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Cited by 9 publications

References 19 publications

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Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B

et al. 1991

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Cells expressing alpha- and gamma-interferon were localized in the liver tissue of patients with chronic hepatitis B by means of light and electron microscopy using monoclonal antibodies. Interferon-positive cells were regularly seen in the infiltrating mononuclear cells, and the number showed a good correlation with the degree of the necroinflammatory activity of the disease. In chronic persistent hepatitis and in normal livers, they were infrequent or virtually absent. alpha-Interferon was shown to be positive in lymphocytes, polymorphonuclear leukocytes and fibroblasts, Kupffer cells and, weakly, in the cytoplasm of a few hepatocytes in cases of active hepatitis, whereas gamma-interferon was demonstrated only in lymphocytes. The expression of human leukocyte class I antigens on hepatocytes showed a close association with the number of interferon-producing cells, but not with the presence of virus particles and HBcAg in liver cells, when studied using electron microscopy and double-labeling. Interferon seems to be an important regulator of the local immune response in the liver in patients with chronic hepatitis B. Its functions may play a role in inducing the human leukocyte class I antigen expression on hepatocytes, thus enhancing the elimination of virus-containing hepatocytes by major histocompatibility complex-restricted cytotoxic lymphocytes.

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Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B

et al. 1991

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Serum levels of interferon-α and-γ in acute and chronic hepatitis B virus infection

et al. 1995

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To evaluate the potential implication of in vivo interferon production in the pathogenesis of different forms of acute and chronic hepatitis B virus infection, serum levels of interferon-alpha and -gamma were measured using immunoassay techniques in 20 patients with acute hepatitis B who subsequently cleared the virus (group Ia), 8 patients with acute hepatitis B who became HBsAg carriers (group Ib), 55 patients with chronic hepatitis B (group II), and 15 healthy controls. None of the controls had interferon-alpha or -gamma detectable in serum, while 15% and 100% of group Ia patients, 25% and 100% of group Ib patients, and 22% and 15% of group II patients, had raised serum levels of interferon-alpha and -gamma, respectively. Serum interferon-gamma was detected significantly more frequently in group Ia and Ib patients than in controls and in group II patients. Among patients with acute hepatitis B, serum levels of interferon-alpha and -gamma showed no significant difference between group Ia and group Ib patients. Among patients with chronic hepatitis B, interferon-alpha was detected significantly more frequently in patients with serum HBV-DNA (31.4% or 11/35) than in those without (5% or 1/20), whereas interferon-gamma was detected significantly more frequently in patients with chronic active hepatitis (28% or 7/25) than in those with chronic persistent hepatitis (3.3% or 1/30). In conclusion, in acute hepatitis B, serum levels of interferon-alpha and -gamma did not show a significant difference between patients who subsequently cleared the virus and those who became HBsAg carriers.(ABSTRACT TRUNCATED AT 250 WORDS)

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2′,5′ oligoadenyIate synthetase activity in peripheral blood mononuclear cells and serum during interferon treatment of chronic non-A, non-B hepatitis

et al. 1991

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The 2'-5' oligoadenylate synthetase (2-5 AS) activity of peripheral blood mononuclear cells and serum was measured in 23 patients with chronic non-A, non-B hepatitis during interferon therapy, 16 of whom were found to have antibody to hepatitis C virus (anti-HCV). Patients received a daily dose of either 1 million, 3 million or 6 million units of human interferon-alpha or -beta for 4 to 6 weeks. Before treatment, the 2-5 AS activity was not significantly different from that in normal control subjects or patients with chronic hepatitis B. However, during treatment the 2-5 AS activity increased 2- to 41-fold from the initial level. Alanine aminotransferase (ALT) levels normalized promptly after the start of treatment in 15 (65.2%) of the 23 patients, but remained elevated in the remaining 8 (34.8%). Six (40%) of the 15 patients showed consistently normal ALT levels for 6 to 30 months after the end of treatment. There was no significant difference between the responders and non-responders in the pattern of change of 2-5 AS activity, but pretreatment activity levels in peripheral blood mononuclear cells were significantly higher (P less than 0.001) in the patients whose ALT levels did not normalize during treatment. The frequency of patients with a positive anti-HCV was significantly higher (P less than 0.05) in the group in which ALT levels normalized. Therefore, these findings suggest that the pretreatment 2-5 AS activity and the detection of anti-HCV may be useful parameters for predicting the response to interferon therapy.

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Elevated levels of 2′,5′-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during acute exacerbation of chronic hepatitis B

Cited by 9 publications

References 19 publications

Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B

Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B

Serum levels of interferon-α and-γ in acute and chronic hepatitis B virus infection

2′,5′ oligoadenyIate synthetase activity in peripheral blood mononuclear cells and serum during interferon treatment of chronic non-A, non-B hepatitis

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