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

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 (PP = 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.准确评估慢性丙型肝炎（CHC）所致肝脏坏死性炎症，对预后预测与治疗策略制定均具有关键价值，这一点在丙氨酸氨基转移酶（ALT）水平正常的CHC患者中尤为显著。现有研究证实，鞘脂类（sphingolipids）与丙型肝炎病毒感染存在紧密关联。本研究旨在筛选与肝脏坏死性炎症相关的血浆鞘脂类标志物。本研究纳入120例初治CHC患者，其中64例患者ALT水平正常（P=0.01），且其诊断效能接近ALT相关指标（曲线下面积AUC=0.78）。然而，在ALT水平正常的CHC患者中，己糖神经酰胺（HexCer, d18∶1/22∶0）是识别肝脏坏死性炎症（G≥2）的独立影响因素（比值比OR=1.02，95%置信区间CI：1.01~1.03）。己糖神经酰胺（HexCer, d18∶1/22∶0）不仅展现出最高的曲线下面积（0.78，P=0.001），同时在所有检测指标中特异性最优。上述结果表明，血浆己糖神经酰胺（HexCer, d18∶1/22∶0）是区分CHC患者肝脏坏死性炎症的潜在标志物。对于ALT水平正常的CHC患者而言，己糖神经酰胺（HexCer, d18∶1/22∶0）区分肝脏坏死性炎症的效能或优于常规血清学指标。