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Lipidomic profiling of plasma in patients with chronic hepatitis C infection

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Abstract

Chronic hepatitis C virus (HCV) infection is a global health issue. Although its progression is reported to be closely associated with lipids, the way in which the plasma lipidome changes during the development of chronic HCV infection in humans is currently unknown. Using an improved quantitative high-throughput lipidomic platform, we profiled 284 lipids in human plasma samples obtained from healthy controls (n = 11) and patients with chronic HCV infection (n = 113). The intrahepatic inflammation grade (IG) of liver tissue was determined by biopsy. Two types of mass spectrometers were integrated into a single lipidomic platform with a wide dynamic range. Compared with previous methods, the performance of this method was significantly improved in terms of both the number of target sphingolipids identified and the specificity of the high-resolution mass spectrometer. As a result, 44 sphingolipids, one diacylglycerol, 43 triglycerides, 24 glycerophosphocholines, and 5 glycerophospho-ethanolamines were successfully identified and quantified. The lipid profiles of individuals with chronic HCV infection were significantly different from those of healthy individuals. Several lipids showed significant differences between mild and severe intrahepatic inflammation grades, indicating that they could be utilized as novel noninvasive indicators of intrahepatic IG. Using multivariate analysis, healthy controls could be discriminated from HCV patients based on their plasma lipidome; however, patients with different IGs were not well discriminated. Based on these results, we speculate that variations in lipid composition arise as a result of HCV infection, and are caused by HCV-related digestive system disorders rather than progression of the disease.

Flowchart of the lipidomic platform

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Abbreviations

DG:

Diacylglycerol

HCV:

Hepatitis C virus

HPLC-MS:

High-performance liquid chromatography tandem mass spectrometry

HRMS:

High-resolution mass spectrometry

IG:

Inflammation grade

LDA:

Lipid data analyzer

LTQ-FT:

Hybrid ion trap–Fourier transform mass spectrometry

MS:

Mass spectrometry

MTBE:

Methyl-tert-butyl ether

OPLS-DA:

Orthogonal partial least squares discriminant analysis

PC:

Glycerophosphocholine

PE:

Glycerophosphoethanolamine

QC:

Quality control

QQQ:

Triple quadrupole mass spectrometry

SM:

Sphingomyelin

TG:

Triglyceride

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Acknowledgments

The Ministry of Science and Technology of the People’s Republic of China (2012ZX09301002-006), and the National Science and Technology Key Project on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment” (2012ZX10002004-006) are acknowledged.

Conflict of interest disclosure

The authors declare no competing financial interest.

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Authors and Affiliations

  1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 2 Nanwei Road, Beijing, 100050, China

    Feng Qu, Cai-Sheng Wu, Zhi-Xin Jia & Jin-Lan Zhang

  2. Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China

    Su-Jun Zheng & Zhong-Ping Duan

Authors
  1. Feng Qu
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  2. Su-Jun Zheng
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  5. Jin-Lan Zhang
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Corresponding authors

Correspondence to Jin-Lan Zhang or Zhong-Ping Duan.

Additional information

Feng Qu and Su-Jun Zheng are co-first author. Jin-Lan Zhang and Zhong-Ping Duan are co-correspondence author.

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Qu, F., Zheng, SJ., Wu, CS. et al. Lipidomic profiling of plasma in patients with chronic hepatitis C infection. Anal Bioanal Chem 406, 555–564 (2014). https://doi.org/10.1007/s00216-013-7479-8

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  • DOI: https://doi.org/10.1007/s00216-013-7479-8

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