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

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J Infect Dis. 2011 Mar 11. [Epub ahead of print]

Association of Serum Cytokine Levels with Treatment Response to Pegylated

Interferon and Ribavirin Therapy in Genotype 1 Chronic Hepatitis C Patients.

Yoneda S, Umemura T, Katsuyama Y, Kamijo A, Joshita S, Komatsu M, Ichijo T,

Matsumoto A, Yoshizawa K, Ota M, Tanaka E; the Nagano Interferon Treatment

Research Group.

Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu

University School of Medicine.

Abstract

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.

PMID: 21398397 [PubMed - as supplied by publisher]