Elevated levels of (2'-5') oligoadenylate synthetase activity in chronic hepatitis B with acute exacerbation

We measured (2'-5') oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum in chronic hepatitis B (CHB) with acute exacerbation. Elevated levels of 2-5 AS activity in PBMC and serum in CHB with acute exacerbation were found, while in CHB without...

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Published inKanzo Vol. 29; no. 11; pp. 1431 - 1437
Main Authors OKUNO, Tadao, TAKINO, Tatsuro, TAKEDA, Makoto, ARAI, Ken, SOKAWA, Yoshihiro, MATSUMOTO, Masayuki, SHINDO, Michiko
Format Journal Article
LanguageJapanese
Published The Japan Society of Hepatology 1988
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ISSN0451-4203
1881-3593
DOI10.2957/kanzo.29.1431

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Abstract We measured (2'-5') oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum in chronic hepatitis B (CHB) with acute exacerbation. Elevated levels of 2-5 AS activity in PBMC and serum in CHB with acute exacerbation were found, while in CHB without acute exacerbation the levels were similar to healthy subjects. Increase in 2-5 AS activity was associated with increase in serum aminotransferases rather than that in HBV-associated markers such as DNA polymerase and serum HBV DNA. These suggest that in vivo IFN system may be activated during acute exacerbation in CHB, and that this activation may not be a result of HBV multiplication alone, but also of a host-immune response to HBV multiplication. Three patients among 7 CHB with acute exacerbation were treated with IFN. Before treatment, all of them had elevated 2-5 AS. None of them cleared HBeAg after treatment. This suggests that IFN treatment was not effective during acute exacerbation since in vivo IFN system has already been activated. Measurement of 2-5 AS in CHB may be useful to determine the optimal timing of IFN treatment.
AbstractList We measured (2'-5') oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum in chronic hepatitis B (CHB) with acute exacerbation. Elevated levels of 2-5 AS activity in PBMC and serum in CHB with acute exacerbation were found, while in CHB without acute exacerbation the levels were similar to healthy subjects. Increase in 2-5 AS activity was associated with increase in serum aminotransferases rather than that in HBV-associated markers such as DNA polymerase and serum HBV DNA. These suggest that in vivo IFN system may be activated during acute exacerbation in CHB, and that this activation may not be a result of HBV multiplication alone, but also of a host-immune response to HBV multiplication. Three patients among 7 CHB with acute exacerbation were treated with IFN. Before treatment, all of them had elevated 2-5 AS. None of them cleared HBeAg after treatment. This suggests that IFN treatment was not effective during acute exacerbation since in vivo IFN system has already been activated. Measurement of 2-5 AS in CHB may be useful to determine the optimal timing of IFN treatment.
Author MATSUMOTO, Masayuki
OKUNO, Tadao
TAKINO, Tatsuro
ARAI, Ken
SOKAWA, Yoshihiro
SHINDO, Michiko
TAKEDA, Makoto
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  fullname: TAKEDA, Makoto
  organization: Third Department of Internal Medicine, Kyoto Prefectural University of Medicine
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  organization: Third Department of Internal Medicine, Kyoto Prefectural University of Medicine
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  fullname: SHINDO, Michiko
  organization: Third Department of Internal Medicine, Kyoto Prefectural University of Medicine
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References 13) Bourgeade MF, Besancon F: Induction of 2', 5'-oligoadenylate synthetase by retinoic acid in two transformed human cell lines. Cancer Res, 44: 5355-5360, 1982
6) Liaw Y-F, Chu C-M, Su I-J,: Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology 84: 216-219, 1983
11) Kaplan PM, Greenman RL, Gerin JL,: DNA polymerase associated with human-hepatitis B antigen. J Virol 12: 995-1005, 1973
1) Poitrine A, Chousterman S, Chousterman M,: Lack of in vivo activation of the interferon system in HBsAg-positive chronic active hepatitis. Hepatology 5: 171-174, 1985
8) Tong MJ, Sampliner RE, Govindarajan S,: Spontaneous reactivation of hepatitis B in chinese patients with HBsAg-positive chronic active hepatitis. Hepatology 7: 713-718, 1987
10) Rigby PWJ, Dieckmann M, Rhodes C,: Labeling deoxyribonucleic acid to higher specific activity in vitro by nick translation with DNA polymerase. J Molec Biol 113: 237-251, 1977
9) Berninger M, Hammer M, Hoyer B,: An assay for the detection of the DNA genome of hepatitis B virus in serum. J Med Virology 9: 57-68, 1982
3) Peters M, Davis GL, Dooly JS,: The interferon system in acute and chronic viral hepatitis. Progress in liver diseases 1986, p453-467
14) Zullo JN, Cochran BH, Huang AS,: Platelet-derived growth factor and doublestranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. Cell 43: 793-800, 1985
5) 進藤道子,奥野忠雄,松本昌之,他:B型慢性肝炎でのインターフェロン療法時の血清中2'-5' oligoadenylate synthetase活性測定の臨床的意義.肝臓 28: 675-680, 1987
4) Shindo M, Okuno T, Matsumoto M,: Serum (2'-5') oligoadenylate synthetase activity during interferon treatment of chronic hepatitis B. Hepatology 8: 366-370, 1988
7) Liaw Y-F, Yang S-S, Chen T-J,: Acute exacerbation in hepatitis B e antigen positive chronic type B hepatitis. J Hepatology 1: 227-233, 1985
12) 進藤道子,奥野忠雄,岩田晃,他:B型慢性肝炎のインターフェロン治療時におけるIFN結合能と2-5 AS誘導能の変動.肝臓 29: 149-157, 1988
2) Pirovino M, Aguet M, Huber M,: Absence of detectable serum interferon in acute and chronic viral hepatitis. Hepatology 6: 654-647, 1986
References_xml – reference: 13) Bourgeade MF, Besancon F: Induction of 2', 5'-oligoadenylate synthetase by retinoic acid in two transformed human cell lines. Cancer Res, 44: 5355-5360, 1982
– reference: 12) 進藤道子,奥野忠雄,岩田晃,他:B型慢性肝炎のインターフェロン治療時におけるIFN結合能と2-5 AS誘導能の変動.肝臓 29: 149-157, 1988
– reference: 3) Peters M, Davis GL, Dooly JS,: The interferon system in acute and chronic viral hepatitis. Progress in liver diseases 1986, p453-467
– reference: 4) Shindo M, Okuno T, Matsumoto M,: Serum (2'-5') oligoadenylate synthetase activity during interferon treatment of chronic hepatitis B. Hepatology 8: 366-370, 1988
– reference: 14) Zullo JN, Cochran BH, Huang AS,: Platelet-derived growth factor and doublestranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. Cell 43: 793-800, 1985
– reference: 11) Kaplan PM, Greenman RL, Gerin JL,: DNA polymerase associated with human-hepatitis B antigen. J Virol 12: 995-1005, 1973
– reference: 2) Pirovino M, Aguet M, Huber M,: Absence of detectable serum interferon in acute and chronic viral hepatitis. Hepatology 6: 654-647, 1986
– reference: 6) Liaw Y-F, Chu C-M, Su I-J,: Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology 84: 216-219, 1983
– reference: 5) 進藤道子,奥野忠雄,松本昌之,他:B型慢性肝炎でのインターフェロン療法時の血清中2'-5' oligoadenylate synthetase活性測定の臨床的意義.肝臓 28: 675-680, 1987
– reference: 10) Rigby PWJ, Dieckmann M, Rhodes C,: Labeling deoxyribonucleic acid to higher specific activity in vitro by nick translation with DNA polymerase. J Molec Biol 113: 237-251, 1977
– reference: 7) Liaw Y-F, Yang S-S, Chen T-J,: Acute exacerbation in hepatitis B e antigen positive chronic type B hepatitis. J Hepatology 1: 227-233, 1985
– reference: 1) Poitrine A, Chousterman S, Chousterman M,: Lack of in vivo activation of the interferon system in HBsAg-positive chronic active hepatitis. Hepatology 5: 171-174, 1985
– reference: 8) Tong MJ, Sampliner RE, Govindarajan S,: Spontaneous reactivation of hepatitis B in chinese patients with HBsAg-positive chronic active hepatitis. Hepatology 7: 713-718, 1987
– reference: 9) Berninger M, Hammer M, Hoyer B,: An assay for the detection of the DNA genome of hepatitis B virus in serum. J Med Virology 9: 57-68, 1982
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Snippet We measured (2'-5') oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum in chronic hepatitis B (CHB) with acute...
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Title Elevated levels of (2'-5') oligoadenylate synthetase activity in chronic hepatitis B with acute exacerbation
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