title: Plasma sphingolipids as potential indicators of hepatic necroinflammation in patients with chronic hepatitis C and normal alanine aminotransferase level.
abstract: Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C (CHC) is crucial for prediction of prognosis and design of therapeutic strategy, which is particularly true for CHC patients with normal alanine aminotransferase (ALT) level. Recent studies have shown that sphingolipids have a close relationship with hepatitis C virus infection. The present study aimed to identify plasma sphingolipids related to hepatic necroinflammation. We included 120 treatment-naïve CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC patients who underwent liver biopsies were subjected to Scheuer scoring analysis for scope of hepatic inflammation. Plasma sphingolipids were detected by high-performance liquid chromatography tandem mass spectrometry. Our results showed 44 plasma sphingolipids were detected altogether. Of all detected sphingolipids, hexosylceramide (HexCer) (d18∶1/22∶0) and HexCer (d18∶1/24∶0) showed a significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying hepatic necroinflammation (G≥2), after adjusting other factors, the odds ratio (OR) of HexCer (d18∶1/22∶0) reached 1.01 (95% confidence interval [CI]: 1.00-1.02). Furthermore, the area under the curve (AUC) of HexCer (d18∶1/22∶0) was 0.7 (P = 0.01) and approached that of ALT (AUC = 0.78). However, in CHC patients with normal ALT, HexCer (d18∶1/22∶0) was an independent factor (OR: 1.02, 95% CI: 1.01-1.03) to identify the hepatic necroinflammation (G≥2). HexCer (d18∶1/22∶0) not only showed the largest AUC (0.78, P = 0.001), but also exhibited the highest specificity of all indicators. These results indicate that plasma HexCer (d18∶1/22∶0) is a potential indicator to distinguish hepatic necroinflammation in CHC patients. For CHC with normal ALT, the ability of HexCer (d18∶1/22∶0) to distinguish hepatic necroinflammation might be superior to conventional serum indicators.
authors.affiliation: The First Clinical Medical School, Lanzhou University, Lanzhou, China; Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qu
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Zheng
authors.affiliation: Evergreen Wellness Center, Kansas College of Chinese Medicine, Wichita, Kansas, United States of America.
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Ren
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Wu
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pathology, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Duan
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001706:Biopsy; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D013107:Sphingolipids / Q000097:blood*
chemical_list: D015415:Biomarkers; D013107:Sphingolipids; D000410:Alanine Transaminase
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