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High Serum Palmitic Acid is Associated with Low Antiviral Effects of Interferon-Based Therapy for Hepatitis C Virus

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Lipids

Abstract

Hepatitis C virus (HCV) infection alters fatty acid synthesis and metabolism in association with HCV replication. The present study examined the effect of serum fatty acid composition on interferon (IFN)-based therapy. Fifty-five patients with HCV were enrolled and received IFN-based therapy. Patient characteristics, laboratory data (including fatty acids), and viral factors that could be associated with the anti-HCV effects of IFN-based therapy were evaluated. The effects of individual fatty acids on viral replication and IFN-based therapy were also examined in an in-vitro system. Multivariate logistic regression analysis showed that the level of serum palmitic acid before treatment and HCV genotype were significant predictors for rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR). High levels of palmitic acid inhibited the anti-HCV effects of IFN-based therapy. HCV replication assays confirmed the inhibitory effects of palmitic acid on anti-HCV therapy. The concentration of serum palmitic acid is an independent predictive factor for RVR, EVR, and SVR in IFN-based antiviral therapy. These results suggest that the effect of IFN-based antiviral therapy in patients with HCV infection might be enhanced by treatment that modulates palmitic acid levels.

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Abbreviations

AUC:

Area under curve

BMI:

Body mass index

DMEM:

Dulbecco’s modified Eagle’s medium

EVR:

Early virological response

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

HCC:

Hepatocellular carcinoma

HBc:

Hepatitis B core

HBs-Ag:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

IFN:

Interferon

IL-28B:

Interleukin-28B

ISDR:

Interferon sensitivity-determining region

NPV:

Negative predictive value

NS5:

Nonstructural-5

PEG-IFN:

Pegylated interferon

PPV:

Positive predictive value

RBV:

Ribavirin

ROC:

Receiver operating characteristics

RVR:

Rapid virological response

SVR:

Sustained virological response

PCR:

Polymerase chain reaction

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research [JSPS KAKENHI 23700907 to T.M.; JSPS KAKENHI 21590848 to Y.H.] from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and a Grant-in-Aid for Scientific Research and Development from the Japanese Ministry of Health, Labor and Welfare to Y.H. We thank Ms. Satomi Yamanaka, Ms. Chie Matsugi and Ms. Sakiko Inoh for excellent technical assistance. The sequence of the probe and primers for the TaqMan assay for detecting rs8099917 was kindly provided by Dr. Yasuhito Tanaka (Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan), and rs12979860 was provided by Dr. David B. Goldstein (Center for Human Genome Variation, Duke University, Durham, NC, USA). The HCV replication system with pJFH1-full was kindly provided by Dr. Takaji Wakita (Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan), and that with pT7-flHCV-Rz was provided by Dr. Raymond T. Chung (Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA). We also thank Dr. Francis V. Chisari (Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA) for providing the Huh7.5.1 human cancer cell lines.

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Authors and Affiliations

  1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan

    Teruki Miyake, Yoichi Hiasa, Masashi Hirooka, Yoshio Tokumoto, Takao Watanabe, Shinya Furukawa, Teruhisa Ueda, Shin Yamamoto, Teru Kumagi, Masanori Abe, Bunzo Matsuura & Morikazu Onji

  2. Internal Medicine, Saiseikai Matsuyama Hospital, Matsuyama, Ehime, 791-8026, Japan

    Hiroaki Miyaoka

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  1. Teruki Miyake
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Correspondence to Yoichi Hiasa.

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Miyake, T., Hiasa, Y., Hirooka, M. et al. High Serum Palmitic Acid is Associated with Low Antiviral Effects of Interferon-Based Therapy for Hepatitis C Virus. Lipids 47, 1053–1062 (2012). https://doi.org/10.1007/s11745-012-3716-8

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  • DOI: https://doi.org/10.1007/s11745-012-3716-8

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