Association of Serum Cytokine Levels With Treatment Response to Pegylated Interferon and Ribavirin Therapy in Genotype 1 Chronic Hepatitis C Patients

• Published in: The Journal of infectious diseases Vol. 203; no. 8; pp. 1087 - 1095
• Main Authors: Yoneda, Suguru, Umemura, Takeji, Katsuyama, Yoshihiko, Kamijo, Atsushi, Joshita, Satoru, Komatsu, Michiharu, Ichijo, Tetsuya, Matsumoto, Akihiro, Yoshizawa, Kaname, Ota, Masao, Tanaka, Eiji
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.04.2011
• Subjects: Amino Acid Substitution; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; Antivirals; Biological and medical sciences; Biomarkers; Chronic hepatitis; Cytokines; Cytokines - blood; Fundamental and applied biological sciences. Psychology; Genotypes; Health outcomes; Hepatitis; Hepatitis C Antigens - blood; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Human viral diseases; Humans; Infections; Infectious diseases; Interferon-alpha - administration & dosage; Interferon-alpha - therapeutic use; Interferons; Medical sciences; Microbiology; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - therapeutic use; Recombinant Proteins; Ribavirin - administration & dosage; Ribavirin - therapeutic use; Sensitivity and Specificity; Viral Core Proteins - blood; Viral diseases; Viral hepatitis; Virology; Viruses; Human; Cytokine; Hepatic disease; Genotype; Ribavirin; Infection; Treatment; Viral disease; Nucleoside analog; Digestive diseases; Antiviral; Serum; Interferon; Viral hepatitis C
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiq165

Background. We sought to clarify the associations among serum cytokines, amino acid substitutions in the interferon sensitivity-determining region (ISDR) and core region, and treatment outcome of pegylated interferon and ribavirin therapy in genotype 1 hepatitis C virus (HCV)-infected patients. Methods. We quantified a total of 8 serum cytokines before, during, and after treatment in 79 genotype 1 chronic HCV patients. Viral ISDR and core region variants were determined by direct sequencing. Results. High levels of interleukin (IL)-12 and IL-18 and more than 2 mutations in the ISDR were associated with a sustained virological response (SVR). Conversely, high baseline IL-10 levels and glutamine at amino acid 70 of the HCV core protein (Gln70) were significantly associated with a nonresponse to treatment, and patients with Gln70 had significantly higher IL-10 levels. In multivariate analysis, low IL-10, high IL-12, and high IL-18 levels were independently associated with an SVR. These 3 cytokine levels were decreased from baseline levels 4 weeks into treatment and remained low in patients with an SVR. Conclusion. Serum IL-10, IL-12, and IL-18 levels are predictive of the response to HCV treatment with pegylated interferon and ribavirin and are associated with amino acid substitutions in the ISDR and core region.