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Omega-6-derived oxylipin changes in serum of patients with hepatitis B virus-related liver diseases

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Abstract

Introduction

Chronic hepatitis B virus (HBV) infection is the main etiologic risk factor for hepatocellular carcinoma (HCC). Early studies indicated that the increase of omega-6-derived oxylipins may be involved in the pathogenesis of HBV-related HCC, yet their changes during the distinct clinical phases of chronic HBV infection remain unclear. To fill this gap, in this study we investigated the omega-6-derived oxylipin profiles in patients with three major clinical stages of chronic HBV infection (chronic hepatitis B, liver cirrhosis, and HCC).

Methods

Eighteen omega-6-derived oxylipins were quantified in serum samples of 34 patients with chronic hepatitis B, 46 patients with HBV-related liver cirrhosis, 38 patients with HBV-related HCC, and 50 healthy controls using liquid chromatography tandem mass spectrometry.

Results

Seven oxylipins were found to be altered in patients with HBV-related liver diseases, including 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME), 12,13-DiHOME, 14,15-dihydroxyeicosatrienoic acid (14,15-DiHETrE), 13-hydroxyoctadecadienoic acid (13-HODE), 12-hydroxyeicosatetraenoic acid (12-HETE), 11-HETE, and thromboxane B2 (TXB2). Of these, three oxylipins derived from the cytochrome P450 (CYP450) pathways including 9,10-DiHOME, 12,13-DiHOME, and 14,15-DiHETrE were found to be associated with the levels of α-fetoprotein (AFP), a tumor marker. In combination with AFP, age, and gender, a combination of these seven differential oxylipins could significantly enhance the prediction of HBV-related liver diseases, particularly for liver cirrhosis (p < 0.05).

Conclusion

This study for the first time shows the correlations between CYP450-derived oxylipins and the progression of chronic HBV infection, and sheds a new light on the surveillance of HBV-related live diseases using oxylipins.

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Acknowledgements

We thank all participants for their invaluable contribution to the study. This study was partially supported by NUS secondment Funds to CNO (706-000-005-133) and NUS Environmental Research Institute (NERI) (608-000-007-731). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    Authors and Affiliations

    1. Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, Level 11, 12 Science Drive 2, Singapore, 117549, Singapore

      Yonghai Lu, Jinling Fang, Li Zou & Choon Nam Ong

    2. Institute of Nutrition and Health, Qingdao University, Qingdao, Shandong, China

      Yonghai Lu

    3. Singapore-MIT Alliance for Research & Technology (SMART), Singapore, Singapore

      Liang Cui

    4. NUS Environment Research Institute, National University of Singapore, Singapore, Singapore

      Xu Liang & Choon Nam Ong

    5. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore, 119228, Singapore

      Seng Gee Lim & Yock-Young Dan

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    1. Yonghai Lu
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    2. Jinling Fang
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    3. Li Zou
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    4. Liang Cui
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    Correspondence to Yonghai Lu or Yock-Young Dan.

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    The authors declare that they have no conflict of interest.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    Informed consent was obtained from all individual participants included in the study.

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    Yonghai Lu and Jinling Fang have contributed equally to this work.

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    Lu, Y., Fang, J., Zou, L. et al. Omega-6-derived oxylipin changes in serum of patients with hepatitis B virus-related liver diseases. Metabolomics 14, 26 (2018). https://doi.org/10.1007/s11306-018-1326-z

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