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Factors influencing the response to interferon therapy in chronic hepatitis C. Studies on viral genotype and induction of 2',5'-oligoadenylate synthetase in the liver and peripheral blood cells

Grander, D; Hultcrantz, R; Weiland, O; Xu, B; Sangfelt, O; Bjorklund, A C; Befrits, R; Bjorkholm, M; Gruber, A and Kinnman, N, et al. (1996) In Scandinavian Journal of Gastroenterology 31(6). p.604-611
Abstract
BACKGROUND: The mechanism behind the antiviral action of interferon (IFN) therapy in chronic hepatitis C virus (HCV) infection is not well understood, and, furthermore, few factors have been shown to be good predictors of a favourable response to IFN treatment in chronic HCV infection. METHODS: Freshly explanted liver cells and peripheral blood mononuclear cells (PBMC) from 80 patients with chronic HCV infection were used to study the capacity of IFN to induce the enzyme 2',5'-oligoadenylate synthetase (2'5'-AS) in vitro. The HCV genotype was determined in 53 patients. The induction of 2'5'-AS was correlated to the results of IFN-alpha treatment in 36 patients. RESULTS: Normalization of transaminases during IFN treatment was significantly... (More)
BACKGROUND: The mechanism behind the antiviral action of interferon (IFN) therapy in chronic hepatitis C virus (HCV) infection is not well understood, and, furthermore, few factors have been shown to be good predictors of a favourable response to IFN treatment in chronic HCV infection. METHODS: Freshly explanted liver cells and peripheral blood mononuclear cells (PBMC) from 80 patients with chronic HCV infection were used to study the capacity of IFN to induce the enzyme 2',5'-oligoadenylate synthetase (2'5'-AS) in vitro. The HCV genotype was determined in 53 patients. The induction of 2'5'-AS was correlated to the results of IFN-alpha treatment in 36 patients. RESULTS: Normalization of transaminases during IFN treatment was significantly associated with 2'5'-AS levels in liver cells cultured in the absence of IFN. A similar tendency, although not statistically significant, was found for IFN-induced levels of 2'5'-AS in liver cells. No such associations were found when PBMC were analysed. Six patients showed a sustained biochemical response. These six did not deviate significantly from the remaining patients with regard to base-line or IFN-induced levels of 2'5'-AS in liver cells or PBMC. Eradication of HCV RNA during IFN treatment did not correlate with 2'5'-AS levels in liver cells. Comparison of HCV genotype and clinical response showed that patients with genotype 3a had the most favourable outcome. No association was found between liver histology and treatment outcome. CONCLUSION: These data imply that direct effects of IFN on liver cells are of importance for the response to IFN treatment. (Less)
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keywords
Hepatitis C, interferon, 2', 5'-oligoadenylate synthetase, predictive assay, viral genotype
in
Scandinavian Journal of Gastroenterology
volume
31
issue
6
pages
604 - 611
publisher
Taylor & Francis
external identifiers
  • pmid:8789901
  • scopus:0029976669
ISSN
1502-7708
DOI
10.3109/00365529609009135
language
English
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yes
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4bfe4b08-f7d3-472b-a46c-975b93271867 (old id 1109957)
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2008-07-23 10:33:34
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2017-01-01 07:09:23
@article{4bfe4b08-f7d3-472b-a46c-975b93271867,
  abstract     = {BACKGROUND: The mechanism behind the antiviral action of interferon (IFN) therapy in chronic hepatitis C virus (HCV) infection is not well understood, and, furthermore, few factors have been shown to be good predictors of a favourable response to IFN treatment in chronic HCV infection. METHODS: Freshly explanted liver cells and peripheral blood mononuclear cells (PBMC) from 80 patients with chronic HCV infection were used to study the capacity of IFN to induce the enzyme 2',5'-oligoadenylate synthetase (2'5'-AS) in vitro. The HCV genotype was determined in 53 patients. The induction of 2'5'-AS was correlated to the results of IFN-alpha treatment in 36 patients. RESULTS: Normalization of transaminases during IFN treatment was significantly associated with 2'5'-AS levels in liver cells cultured in the absence of IFN. A similar tendency, although not statistically significant, was found for IFN-induced levels of 2'5'-AS in liver cells. No such associations were found when PBMC were analysed. Six patients showed a sustained biochemical response. These six did not deviate significantly from the remaining patients with regard to base-line or IFN-induced levels of 2'5'-AS in liver cells or PBMC. Eradication of HCV RNA during IFN treatment did not correlate with 2'5'-AS levels in liver cells. Comparison of HCV genotype and clinical response showed that patients with genotype 3a had the most favourable outcome. No association was found between liver histology and treatment outcome. CONCLUSION: These data imply that direct effects of IFN on liver cells are of importance for the response to IFN treatment.},
  author       = {Grander, D and Hultcrantz, R and Weiland, O and Xu, B and Sangfelt, O and Bjorklund, A C and Befrits, R and Bjorkholm, M and Gruber, A and Kinnman, N and Reichard, O and Widell, Anders and Einhorn, S},
  issn         = {1502-7708},
  keyword      = {Hepatitis C,interferon,2',5'-oligoadenylate synthetase,predictive assay,viral genotype},
  language     = {eng},
  number       = {6},
  pages        = {604--611},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {Factors influencing the response to interferon therapy in chronic hepatitis C. Studies on viral genotype and induction of 2',5'-oligoadenylate synthetase in the liver and peripheral blood cells},
  url          = {http://dx.doi.org/10.3109/00365529609009135},
  volume       = {31},
  year         = {1996},
}