Plasma Sphingolipids as Potential Indicators of Hepatic Necroinflammation in Patients with Chronic Hepatitis C and Normal Alanine Aminotransferase Level

Abstract

? 2014 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.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-na???ve 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.