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Elevated plasma sphingomyelin (d18:1/22:0) is closely related to hepatic steatosis in patients with chronic hepatitis C virus infection

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Abstract

Hepatic steatosis affects disease progression in patients with chronic hepatitis C virus (HCV) infection. We investigated the plasma sphingolipid profile in patients with chronic hepatitis C (CHC) and whether there was an association between HCV-related steatosis and plasma sphingolipids. We used high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) to analyze plasma sphingolipids in 120 interferon-naïve, non-diabetic, and non-obese CHC patients. Hepatic steatosis was defined as ≥5 % hepatocytes with fat based on histopathological analysis. Blood biochemical indicators and HCV load and genotype were also determined. Thirty-six (30.0 %) of 120 patients presented with hepatic steatosis Grades 1–3. Forty-four plasma sphingolipids were detected. Plasma sphingomyelin (SM) (d18:1/22:0) and ceramide (Cer) (d18:1/24:0)-1-P correlated with steatosis grade (r = 0.22, p = 0.015; r = −0.23, p = 0.012, respectively). SM (d18:1/22:0) [odds ratio (OR) = 1.12] and Cer (d18:1/24:0)-1-P (OR = 0.88) were independent factors for the presence of hepatic steatosis in CHC patients. The area under the curve (AUC) of SM (d18:1/22:0) and Cer (d18:1/24:0)-1-P was 0.637 and 0.638, respectively, to identify the presence of steatosis. Further analysis for genotype 2 CHC showed that only SM (d18:1/22:0) was independently linked to steatosis (OR = 1.21). The AUC of SM (d18:1/22:0) to identify hepatic steatosis in genotype 2 CHC was 0.726. Its sensitivity and negative predictive value reached 0.813 and 0.886, respectively. This study suggested that altered plasma SM (d18:1/22:0) was closely related to hepatic steatosis in chronic HCV infection, especially with genotype 2. Experimental studies are needed to determine further the underlying mechanisms responsible for these associations.

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Acknowledgments

This work was funded by the National Science and Technology Key Project of China on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment” (2012ZX10002004-006, 2012ZX10004904-003-001, 2013ZX10002002-006); Ministry of Science and Technology of China (2012ZX09301002-006); The High Technical Personnel Training Item in Beijing Health System (2011-3-083); The Beijing Municipal Science & Technology Commission (no. Z131107002213019); The Special Scientific Research Fund for Beijing Health Development (2011-2018-04); YouAn Scientific Research Fund for Liver Disease and HIV/AIDS (BJYAH-2011-045).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China

    J.-F. Li, S.-J. Zheng, H.-L. Wu, M. Liu, S. Liu, Y. Ren, Y. Chen & Z.-P. Duan

  2. The First Clinical Medical School, Lanzhou University, 1 Donggangxi Road, Lanzhou, 730000, China

    J.-F. Li

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

    F. Qu & J.-L. Zhang

  4. Institute of Liver Diseases, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China

    F. Ren

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  1. J.-F. Li
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Corresponding authors

Correspondence to Z.-P. Duan or J.-L. Zhang.

Additional information

Jun-Feng Li, Feng Qu, and Su-Jun Zheng contributed equally to this work.

Zhong-Ping Duan and Jin-Lan Zhang contributed equally to this work and should be considered as co-corresponding authors.

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Supplementary Table 1

(DOC 56 kb)

Supplementary Fig. 1

Relation between Cer (d18:1/24:0)-1-P and hepatic steatosis type in CHC. a The p-value (0.109) was acquired by one-way analysis of variance among three groups, and p-values between two groups were analyzed by the least significant difference t-test. b The p-value was acquired by the independent-samples t-test. c The p-value was acquired by the independent-samples t-test. (GIF 31 kb)

High Resolution Image (TIFF 583 kb)

Supplementary Fig. 2

Relation between SM (d18:1/22:0) and hepatic steatosis type in CHC. a The p-value (0.287) was acquired by one-way analysis of variance among three groups, and p-values between two groups were analyzed by the least significant difference t-test. b The p-value was acquired by the independent-samples t-test. c The p-value was acquired by the independent-samples t-test. (GIF 31 kb)

High Resolution Image (TIFF 599 kb)

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Li, JF., Qu, F., Zheng, SJ. et al. Elevated plasma sphingomyelin (d18:1/22:0) is closely related to hepatic steatosis in patients with chronic hepatitis C virus infection. Eur J Clin Microbiol Infect Dis 33, 1725–1732 (2014). https://doi.org/10.1007/s10096-014-2123-x

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  • DOI: https://doi.org/10.1007/s10096-014-2123-x

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