Long-term response to interferon alpha is unrelated to 'interferon sensitivity determining region' variability in patients with chronic hepatitis C virus-1b infection

Giovanni Squadrito, Maria Elena Orlando, Irene Cacciola, Maria Grazia Rumi, Marco Artini, Antonio Picciotto, Oreste Loiacono, Rocco Siciliano, Massimo Levrero, Giovanni Raimondo

Research output: Contribution to journalArticle

Abstract

Background/Aims: Contradictory data have been reported about the predictive value of the variability in interferon sensitivity determining region (ISDR) of hepatitis C virus (HCV) genotype-1b on response to interferon-alpha (IFN-α) therapy. The aim of this study was to examine this issue in a series of patients with long-term response to IFN treatment. Methods: We retrospectively analyzed 24 patients with chronic HCV genotype- 1b infection treated with IFN-α (total dose median 677, range 216-1350 MU) selected in 6 Italian Liver Units. These patients were defined as true long- term responders (LTR) since they showed persisting biochemical and virological responses to IFN treatment (mean follow-up 38 months). HCV genomes from pretreatment serum samples were amplified and directly sequenced. The ISDR amino-acid sequences obtained were aligned and compared with the published sequence of HCV-J. Results: Amino-acid substitutions were found in 23 of the 24 patients, and 22 of them showed an H to R amino-acid change at codon 2218. Fourteen patients showed only one mutation (at codon 2218), two had 2, five had 3, one had 4 and one had 5 mutations. When we compared the ISDR sequences from the 24 LTR with those of non-responders (NR), we found no significant correlation between the number of mutations and the response to therapy. Conclusions: Our results demonstrate that the persisting efficacy of IFN treatment in patients with chronic HCV is not related to the number of ISDR amino acid substitutions of the infecting viruses. Further studies are needed to verify whether other NS5A sequences outside the ISDR might be involved in the mechanisms of IFN resistance.

Original languageEnglish
Pages (from-to)1023-1027
Number of pages5
JournalJournal of Hepatology
Volume30
Issue number6
DOIs
Publication statusPublished - Jun 1999

Fingerprint

Chronic Hepatitis C
Virus Diseases
Interferon-alpha
Hepacivirus
Interferons
Amino Acid Substitution
Codon
Mutation
Genotype
Therapeutics
Amino Acid Sequence
Genome
Viruses
Amino Acids
Liver
Infection
Serum

Keywords

  • Chronic hepatitis C
  • Direct sequencing
  • Non-structural 5A protein
  • Polymerasae chain reaction
  • Vital genomic heterogeneity

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Long-term response to interferon alpha is unrelated to 'interferon sensitivity determining region' variability in patients with chronic hepatitis C virus-1b infection. / Squadrito, Giovanni; Orlando, Maria Elena; Cacciola, Irene; Rumi, Maria Grazia; Artini, Marco; Picciotto, Antonio; Loiacono, Oreste; Siciliano, Rocco; Levrero, Massimo; Raimondo, Giovanni.

In: Journal of Hepatology, Vol. 30, No. 6, 06.1999, p. 1023-1027.

Research output: Contribution to journalArticle

Squadrito, G, Orlando, ME, Cacciola, I, Rumi, MG, Artini, M, Picciotto, A, Loiacono, O, Siciliano, R, Levrero, M & Raimondo, G 1999, 'Long-term response to interferon alpha is unrelated to 'interferon sensitivity determining region' variability in patients with chronic hepatitis C virus-1b infection', Journal of Hepatology, vol. 30, no. 6, pp. 1023-1027. https://doi.org/10.1016/S0168-8278(99)80255-4
Squadrito, Giovanni ; Orlando, Maria Elena ; Cacciola, Irene ; Rumi, Maria Grazia ; Artini, Marco ; Picciotto, Antonio ; Loiacono, Oreste ; Siciliano, Rocco ; Levrero, Massimo ; Raimondo, Giovanni. / Long-term response to interferon alpha is unrelated to 'interferon sensitivity determining region' variability in patients with chronic hepatitis C virus-1b infection. In: Journal of Hepatology. 1999 ; Vol. 30, No. 6. pp. 1023-1027.
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abstract = "Background/Aims: Contradictory data have been reported about the predictive value of the variability in interferon sensitivity determining region (ISDR) of hepatitis C virus (HCV) genotype-1b on response to interferon-alpha (IFN-α) therapy. The aim of this study was to examine this issue in a series of patients with long-term response to IFN treatment. Methods: We retrospectively analyzed 24 patients with chronic HCV genotype- 1b infection treated with IFN-α (total dose median 677, range 216-1350 MU) selected in 6 Italian Liver Units. These patients were defined as true long- term responders (LTR) since they showed persisting biochemical and virological responses to IFN treatment (mean follow-up 38 months). HCV genomes from pretreatment serum samples were amplified and directly sequenced. The ISDR amino-acid sequences obtained were aligned and compared with the published sequence of HCV-J. Results: Amino-acid substitutions were found in 23 of the 24 patients, and 22 of them showed an H to R amino-acid change at codon 2218. Fourteen patients showed only one mutation (at codon 2218), two had 2, five had 3, one had 4 and one had 5 mutations. When we compared the ISDR sequences from the 24 LTR with those of non-responders (NR), we found no significant correlation between the number of mutations and the response to therapy. Conclusions: Our results demonstrate that the persisting efficacy of IFN treatment in patients with chronic HCV is not related to the number of ISDR amino acid substitutions of the infecting viruses. Further studies are needed to verify whether other NS5A sequences outside the ISDR might be involved in the mechanisms of IFN resistance.",
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AU - Squadrito, Giovanni

AU - Orlando, Maria Elena

AU - Cacciola, Irene

AU - Rumi, Maria Grazia

AU - Artini, Marco

AU - Picciotto, Antonio

AU - Loiacono, Oreste

AU - Siciliano, Rocco

AU - Levrero, Massimo

AU - Raimondo, Giovanni

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N2 - Background/Aims: Contradictory data have been reported about the predictive value of the variability in interferon sensitivity determining region (ISDR) of hepatitis C virus (HCV) genotype-1b on response to interferon-alpha (IFN-α) therapy. The aim of this study was to examine this issue in a series of patients with long-term response to IFN treatment. Methods: We retrospectively analyzed 24 patients with chronic HCV genotype- 1b infection treated with IFN-α (total dose median 677, range 216-1350 MU) selected in 6 Italian Liver Units. These patients were defined as true long- term responders (LTR) since they showed persisting biochemical and virological responses to IFN treatment (mean follow-up 38 months). HCV genomes from pretreatment serum samples were amplified and directly sequenced. The ISDR amino-acid sequences obtained were aligned and compared with the published sequence of HCV-J. Results: Amino-acid substitutions were found in 23 of the 24 patients, and 22 of them showed an H to R amino-acid change at codon 2218. Fourteen patients showed only one mutation (at codon 2218), two had 2, five had 3, one had 4 and one had 5 mutations. When we compared the ISDR sequences from the 24 LTR with those of non-responders (NR), we found no significant correlation between the number of mutations and the response to therapy. Conclusions: Our results demonstrate that the persisting efficacy of IFN treatment in patients with chronic HCV is not related to the number of ISDR amino acid substitutions of the infecting viruses. Further studies are needed to verify whether other NS5A sequences outside the ISDR might be involved in the mechanisms of IFN resistance.

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