Prediction of response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b.

Abstract

Variation at the IL-28B locus was recently reported to be a significant predictive factor of viral response to pegylated-interferon plus ribavirin combination therapy against chronic hepatitis C. Predictive factors for the effect of therapy, including IL-28B polymorphism rs8099917 and viral and clinical factors were investigated. A total of 288 patients were enrolled who were chronically infected with hepatitis C virus (HCV) genotype 1b and treated with combination therapy. Among them, 87 patients completed 48 weeks of therapy without dose reduction or discontinuation. In multivariate regression analysis, the rs8099917 TT genotype was the only independent factor significantly associated with sustained viral response (P = 0.016, OR 61.5), whereas substitutions at amino acid 70 (aa 70) of the HCV core protein (P = 0.038, OR 5.9) and non-TT genotypes (P = 0.002, OR 17.2) were associated with nonvirological response. Both factors were also associated with viral dynamics during the initial stage of the therapy. Correlation analysis revealed that rs8099917 genotype was correlated with γ-glutamyl transpeptidase, hyaluronic acid, and HCV core aa 70. In conclusion, host (IL-28B polymorphism) and viral (aa 70) factors independently affect response to combination therapy.

• Authors: Yoshimasa Hashimoto, Hidenori Ochi, Hiromi Abe, Yasufumi Hayashida, Masataka Tsuge, Fukiko Mitsui, Nobuhiko Hiraga, Michio Imamura, Shoichi Takahashi, C Nelson Hayes, Waka Ohishi, Michaki Kubo, Tatsuhiko Tsunoda, Naoyuki Kamatani, Yusuke Nakamura, Kazuaki Chayama
• Journal: Journal of medical virology (J Med Virol) Vol. 83 Issue 6 Pg. 981-8 (Jun 2011) ISSN: 1096-9071 [Electronic] United States
• PMID: 21503910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• Antiviral Agents
• interferon-lambda, human
• Interferon alpha-2
• Interferon-alpha
• Interleukins
• RNA, Viral
• Recombinant Proteins
• Viral Core Proteins
• nucleocapsid protein, Hepatitis C virus
• Polyethylene Glycols
• Ribavirin
• Interferons
• peginterferon alfa-2b

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Amino Acid Substitution (genetics)
• Antiviral Agents (administration & dosage, pharmacology, therapeutic use)
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (classification, drug effects, genetics)
• Hepatitis C, Chronic (drug therapy, genetics, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, pharmacology, therapeutic use)
• Interferons
• Interleukins (genetics)
• Japan
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage, pharmacology, therapeutic use)
• Polymorphism, Single Nucleotide
• Prognosis
• RNA, Viral (analysis, genetics)
• Recombinant Proteins (administration & dosage, pharmacology, therapeutic use)
• Ribavirin (administration & dosage, pharmacology, therapeutic use)
• Treatment Outcome
• Viral Core Proteins (genetics)
• Viral Load (drug effects)
• Young Adult