Semmo N, Weber T, Idle J R, Beyoğlu D
University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland.
Hepatology Research Group, Department of Clinical Research, University of Bern, Bern, Switzerland.
J Viral Hepat. 2015 Jul;22(7):617-24. doi: 10.1111/jvh.12376. Epub 2014 Dec 9.
To understand the changes in the metabolome of hepatitis C virus (HCV)-infected persons, we conducted a metabolomic investigation in both plasma and urine of 30 HCV-positive individuals using plasmas from 30 HCV-negative blood donors and urines from 30 healthy volunteers. Samples were analysed by gas chromatography-mass spectrometry and data subjected to multivariate analysis. The plasma metabolomic phenotype of HCV-positive persons was found to have elevated glucose, mannose and oleamide, together with depressed plasma lactate. The urinary metabolomic phenotype of HCV-positive persons comprised reduced excretion of fructose and galactose combined with elevated urinary excretion of 6-deoxygalactose (fucose) and the polyols sorbitol, galactitol and xylitol. HCV-infected persons had elevated galactitol/galactose and sorbitol/glucose urinary ratios, which were highly correlated. These observations pointed to enhanced aldose reductase activity, and this was confirmed by real-time quantitative polymerase chain reaction with AKR1B10 gene expression elevated sixfold in the liver. In contrast, AKR1B1 gene expression was reduced 40% in HCV-positive livers. Interestingly, persons who were formerly HCV infected retained the metabolomic phenotype of HCV infection without reverting to the HCV-negative metabolomic phenotype. This suggests that the effects of HCV on hepatic metabolism may be long lived. Hepatic AKR1B10 has been reported to be elevated in hepatocellular carcinoma and in several premalignant liver diseases. It would appear that HCV infection alone increases AKR1B10 expression, which manifests itself as enhanced urinary excretion of polyols with reduced urinary excretion of their corresponding hexoses. What role the polyols play in hepatic pathophysiology of HCV infection and its sequelae is currently unknown.
为了解丙型肝炎病毒（HCV）感染者代谢组的变化，我们对30例HCV阳性个体的血浆和尿液进行了代谢组学研究，使用了30例HCV阴性献血者的血浆和30例健康志愿者的尿液。通过气相色谱 - 质谱法分析样本，并对数据进行多变量分析。发现HCV阳性者的血浆代谢组表型表现为葡萄糖、甘露糖和油酰胺升高，同时血浆乳酸降低。HCV阳性者的尿液代谢组表型包括果糖和半乳糖排泄减少，同时6 - 脱氧半乳糖（岩藻糖）以及多元醇山梨醇、半乳糖醇和木糖醇的尿排泄增加。HCV感染者的半乳糖醇/半乳糖和山梨醇/葡萄糖尿比值升高，且高度相关。这些观察结果表明醛糖还原酶活性增强，实时定量聚合酶链反应证实了这一点，肝脏中AKR1B10基因表达升高了6倍。相比之下，HCV阳性肝脏中AKR1B1基因表达降低了40%。有趣的是，既往感染过HCV的人保留了HCV感染的代谢组表型，未恢复到HCV阴性代谢组表型。这表明HCV对肝脏代谢的影响可能是长期的。据报道，肝细胞癌和几种癌前肝脏疾病中肝脏AKR1B10升高。似乎仅HCV感染就会增加AKR1B10表达，表现为多元醇尿排泄增加，其相应己糖尿排泄减少。目前尚不清楚多元醇在HCV感染及其后遗症的肝脏病理生理学中起什么作用。
