IL28B polymorphism is associated with both side effects and clearance of hepatitis C during interferon-alpha therapy

Francis E. Lotrich, Jennifer Loftis, Robert E. Ferrell, Mordechai Rabinovitz, Peter Hauser

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Interferon-α (IFN-α) treatment for hepatitis C virus (HCV) is complicated by depression and related neurovegetative side effects. Recent genome-wide scans identified IL28B gene polymorphisms that associated with HCV clearance. Whether the IL28B polymorphism is also associated with these adverse effects of IFN-α would affect its clinical usefulness. One hundred thirty-three patients were prospectively examined using the Beck Depression Inventory-II and a Structured Clinical Interview for Diagnostic and Statistical Manual-IV (DSM-IV) during IFN-α treatment. The candidate C/T single-nucleotide polymorphism upstream from IL28B (rs1297860) was genotyped and assessed for association with individual items from the Beck Depression Inventory-II. We confirmed that the IL28B polymorphism was associated with differences in sustained viral response (F = 3.38; P <0.05), with the T/T genotype faring worst. However, the T/T genotype was associated with less appetite (P <0.05), energy (P <0.05), and sleep complaints (P <0.05) during treatment. Only 3.1% of patients with T/T developed major appetite complaints, whereas 10.1% and 8.9% of those with the C/T and C/C genotype did, respectively. Only 10.8% of patients with T/T developed major sleep complaints, whereas 16.1% and 20.7% of those with the C/T and C/C genotype did. However, IL28B genotype did not predict development of major depressive disorder (χ2 = 0.12; P = 0.94). The allele (C) was associated with both better viral clearance and more subjective appetite, energy, and sleep complaints. This has implications for the management of patients with HCV. If genotyping is used to better target therapy, this may co-enrich the population for likelihood of also suffering from these side effects.

Original languageEnglish (US)
Pages (from-to)331-336
Number of pages6
JournalJournal of Interferon and Cytokine Research
Volume31
Issue number3
DOIs
StatePublished - Mar 1 2011

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Hepatitis C
Interferon-alpha
Genotype
Appetite
Hepacivirus
Interferons
Sleep
Depression
Therapeutics
Equipment and Supplies
Single Nucleotide Polymorphism
Alleles
Genome
Interviews
Population
Genes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology
  • Medicine(all)

Cite this

IL28B polymorphism is associated with both side effects and clearance of hepatitis C during interferon-alpha therapy. / Lotrich, Francis E.; Loftis, Jennifer; Ferrell, Robert E.; Rabinovitz, Mordechai; Hauser, Peter.

In: Journal of Interferon and Cytokine Research, Vol. 31, No. 3, 01.03.2011, p. 331-336.

Research output: Contribution to journalArticle

Lotrich, Francis E. ; Loftis, Jennifer ; Ferrell, Robert E. ; Rabinovitz, Mordechai ; Hauser, Peter. / IL28B polymorphism is associated with both side effects and clearance of hepatitis C during interferon-alpha therapy. In: Journal of Interferon and Cytokine Research. 2011 ; Vol. 31, No. 3. pp. 331-336.
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abstract = "Interferon-α (IFN-α) treatment for hepatitis C virus (HCV) is complicated by depression and related neurovegetative side effects. Recent genome-wide scans identified IL28B gene polymorphisms that associated with HCV clearance. Whether the IL28B polymorphism is also associated with these adverse effects of IFN-α would affect its clinical usefulness. One hundred thirty-three patients were prospectively examined using the Beck Depression Inventory-II and a Structured Clinical Interview for Diagnostic and Statistical Manual-IV (DSM-IV) during IFN-α treatment. The candidate C/T single-nucleotide polymorphism upstream from IL28B (rs1297860) was genotyped and assessed for association with individual items from the Beck Depression Inventory-II. We confirmed that the IL28B polymorphism was associated with differences in sustained viral response (F = 3.38; P <0.05), with the T/T genotype faring worst. However, the T/T genotype was associated with less appetite (P <0.05), energy (P <0.05), and sleep complaints (P <0.05) during treatment. Only 3.1{\%} of patients with T/T developed major appetite complaints, whereas 10.1{\%} and 8.9{\%} of those with the C/T and C/C genotype did, respectively. Only 10.8{\%} of patients with T/T developed major sleep complaints, whereas 16.1{\%} and 20.7{\%} of those with the C/T and C/C genotype did. However, IL28B genotype did not predict development of major depressive disorder (χ2 = 0.12; P = 0.94). The allele (C) was associated with both better viral clearance and more subjective appetite, energy, and sleep complaints. This has implications for the management of patients with HCV. If genotyping is used to better target therapy, this may co-enrich the population for likelihood of also suffering from these side effects.",
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