尿液8-OXO-Gsn和8-OXO-dGsn对HBV感染引起肝损伤程度的价值评估

Evaluation of Urinary 8-oxo-Gsn and 8-oxo-d Gsn for the Extent of Liver Damage Caused by HBV Infection

目的探讨尿液中核酸氧化代谢产物8-oxo-Gsn和8-oxo-d Gsn对HBV感染引起肝损伤程度的评估价值。方法收集笔者医院94例慢性乙型肝炎(以下简称慢乙肝)患者行超声引导下肝穿刺活检前的尿液,95例健康者以及25例乙肝表面携带者的随机尿液,采用同位素稀释高效液相-串联质谱法(ID-LC-MS/MS)分析尿液中DNA氧化标志物8-oxod Gsn和RNA氧化标志物8-oxo-Gsn,并结合病理结果和生化指标(ALT和AST),分析各指标之间的相关性,通过ROC曲线评估二者对肝损伤程度的预测价值,并分析8-oxo-Gsn和8-oxo-d Gsn在不同炎症活动度和不同纤维化程度患者中的水平差异。结果实验组中,88.5%(46/52)的男性8-oxo-Gsn高于正常对照组,85.7%(36/42)的女性8-oxo-Gsn高于正常对照组;肝脏炎症程度高的患者(G_3~G_4)尿液中RNA氧化标志物8-oxo-Gsn显著高于炎症程度低的患者(G_0~G_2)(4.28 vs 3.26,χ~2=11.117,P=0.009),纤维化程度高的患者8-oxo-Gsn水平也高于纤维化程度低的患者(3.66 vs 3.29),但未达到显著性水平(χ~2=3.626,P=0.323)。尿液中RNA氧化标志物8-oxo-Gsn对肝脏炎症程度有较好的预测价值(敏感度为82.4%,特异性为75%,AUC=0.813),对纤维化程度有较好的预测价值(敏感度为83.3%,特异性为77.1%,AUC=0.824)。结论尿液中RNA氧化标志物8-oxo-Gsn可能是HBV感染引起的肝损伤严重程度的评估指标。

Objective To explore the evaluation of urine nucleic acid oxidation metabolites 8 - oxo - Gsn and 8 - oxo - dGsn in se- verity of liver damage caused by HBV infection. Methods We collected the urine of 94 cases of patients with chronic hepatitis B infec- tion, 95 cases of healthy people and 25 cases of hepatitis B surface antigen carrier in our hospital. Isotope dilution high performance liquid chromatography - tandem mass spectrometry（ ID - LC - MS/MS） method was used for analyzing urine DNA oxidation indicator 8 - oxo - dGsn and RNA oxidation index 8 - oxo - Gsn, and we combined with the results of pathology and biochemical marker （ ALT and AST） to analyze the correlation. ROC curve was made to evaluate the predictive value of 8 - oxo - Gsn and 8 - oxo - dGsn to the extent of liver damge. We also analyzed the difference of 8 - oxo - Gsn and 8 - oxo - dGsn in different degrees of inflammation and different degrees of fibrosis. Results 88.5% （46/52） of the male 8 - oxo - Gsn in experimental group was higher than the control group and 85.7% （36/ 42） of the female 8 - oxo - Gsn in experimental group was higher than the control group. Urine RNA oxidation marker 8 - oxo - Gsn was significantly higher in high degree of liver inflammation （ G3 - G4 ） than low degree of liver inflammation （ GO - G2 ） （4.98 vs 3.72 ,X2 = 11.117,P = 0. 009）. The level of 8 - oxo - Gsn in patients with a high fibrosis degree was also higher than that in patients with low fibro- sis degree （3.66 vs 3.29） , but not at a significant level（x2 = 3. 626,P = 0. 323 ）. RNA oxidation index in urine 8 - oxo - Gsn had a good predictive value for liver inflammation （sensitivity 82.4% , specificity 75% , AUC = 0. 813） and also had a good predictive value for the degree of fibrosis （ sensitivity 83.3% , specificity 77.1% , AUC = 0. 824）. Conclusion Urine RNA oxidation marker 8 - oxo - Gsn may be a good assessment marker for the degree of liver damage caused by HBV infection.