南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (02): 147-.

• •    下一篇

血浆游离DNA用于判断乙型肝炎相关慢加急性肝衰竭的预后—先锋试验结果

李梵,闫涛,李克,牟劲松,苏海滨,王慧芬   

  1. 1解放军医学院,北京100853;解放军302 医院2重症监护中心,3肝衰竭诊断和治疗中心,4肝纤维化无创诊疗中心,北京100039
  • 出版日期:2014-02-20 发布日期:2014-02-20

Plasma cell-free DNA for predicting outcomes of patients with
HBV-related acute-on-chronic liver failure: a pilot study

  1. 1解放军医学院,北京100853;解放军302 医院2重症监护中心,3肝衰竭诊断和治疗中心,4肝纤维化无创诊疗中心,北京100039
  • Online:2014-02-20 Published:2014-02-20

摘要: 目的血浆游离DNA(cfDNA)的升高在多种疾病状态下(肿瘤、外伤等)与不良预后相关。进一步研究cfDNA在乙型慢加
急性肝衰竭(HBV-ACLF)中的诊断和治疗作用。方法38名入住ICU的HBV-ACLF患者,根据出院时预后,分为好转组与恶化
组。收集住院时和出院时外周血标本,应用real-time PCR定量检测血浆cfDNA,同时计算患者MELD分值。结果住院时好转
组患者cfDNA水平低于恶化组患者(P=0.044),在出院时两组差异更加明显(P<0.001)。但住院时两组MELD分值无显著差
别。患者cfDNA水平与MELD分值、TBIL及INR等水平有显著相关。通过绘制ROC曲线发现,出院时cfDNA对HBV-ACLF
的诊断能力最强(曲线下面积0.960),随后是出院和入院cfDNA水平的差值(ΔcfDNA)(曲线下面积0.923)和住院时cfDNA水
平(曲线下面积0.667)。结论cfDNA有希望成为HBV-ACLF新的诊断和预后指标。

Abstract: Objective Cell-free DNA (cfDNA) was shown to be a prognostic marker for diverse pathological states in the Intense
Care Unit, but little is known of the role of cfDNA in HBV-related acute-on-chronic liver failure (ACLF). We hypothesize that
cfDNA can also be a promising prognostic as well as a diagnostic marker in patients with HBV-related ACLF. Methods
Thirty-eight patients with HBV-related ACLF admitted in the Intense Care Unit were enrolled in the study. The patients were
divided, according to the improvement of liver function at discharge, into favorable prognosis group (group 1, n=17) and poor
prognosis group (group 2, n=19). Plasma samples were collected from each patient at hospitalization and at discharge to
measure cfDNA by real-time quantitative PCR. MELD score was calculated at the same time points. Results The average level
of cfDNA of group 1 was lower than that of group 2 both at the time of hospitalization (P=0.044) and at discharge (P<0.001).
There was no difference in MELD score between the two groups at hospitalization. Significant correlations were found of
cfDNA levels with the MELD score, TBIL, CRE and INR both at hospitalization (γ=0.662, P<0.001; γ=0.356, P=0.033; γ=0.360, P=
0.031; γ=0.570, P<0.001, respectively) and at discharge (γ=0.854, P<0.001; γ=0.821, P<0.001; γ=0.650, P<0.001; γ=0.638, P<0.001,
respectively). The ROC curve showed that cfDNA level at discharge was optimal in diagnosing ACLF with an area under curve
(AUC) value of 0.96, followed by ΔcfDNA (AUC value of 0.923) and cfDNA level at hospitalization (AUC value of 0.667). The
MELD scores had an AUC value of only 0.545 at the time of hospitalization. Conclusion cfDNA may serve as a promising
prognostic and diagnostic marker for predicting in-hospital prognosis of HBV-related ACLF within 2 to 8 weeks.