HBV相关慢加急性肝衰竭患者体内细胞因子表达及动态变化的研究

Expression and dynamic changes of cytokine levels in patients with HBV-related acute-on-chronic liver failure

目的探讨乙型肝炎相关慢加急性肝衰竭(HBV-related acute-on-chronic liver failure,HBV-ACLF)患者体内细胞因子表达及动态变化的临床意义。方法选择我院2010年3—10月收治的HBV-ACLF患者43例(HBV-ACLF组),同时选取同期慢性乙型肝炎(chronic hepatitis B,CHB)患者46例(CHB组)和20例健康对照者(健康对照组)。采用ELISA法检测3组血清中白细胞介素(interleukin,IL)-1β、IL-6、IL-10、转化生长因子(transforming growth factor,TGF)-β1和肿瘤坏死因子(tumor necrosis factor,TNF)-α水平,同时检测各项临床指标。对43例HBV-ACLF患者进行为期3周的随访,动态观察血清中细胞因子水平的变化趋势。结果 HBV-ACLF组IL-1β、IL-6、IL-10和TGF-β1水平均高于CHB组和健康对照组(P均<0.05),HBV-ACLF组TNF-α水平高于健康对照组(P<0.05)。HBV-ACLF组IL-6水平与TGF-β1水平、HBVDNA、终末期肝病模型分值均呈正相关(r=0.403,P<0.01;r=0.322,P<0.05;r=0.338,P<0.05);IL-10水平与CHE呈正相关(r=0.411,P<0.01)、与Na+呈负相关(r=-0.529,P<0.01);TGF-β1水平与CHE呈正相关(r=0.407,P<0.01)。HBV-ACLF中、晚期组IL-1水平均高于早期组(P均<0.05),中期组TGF-β1水平高于早期组(P<0.05),治愈好转组IL-6、TGF-β1、TNF-α水平呈逐渐下降的趋势,随访第3周时IL-6、TGF-β1水平均低于无效死亡组(P均<0.05)。结论 HBV-ACLF患者体内促炎细胞因子和抗炎细胞因子均出现紊乱,细胞因子的表达及动态变化对预测HBV-ACLF患者疾病进展和预后有很好的临床意义。

Objective To investigate clinical significance of expression and dynamic changes of cytokine levels in HBV-relat- ed acute-on-chronic liver failure （HBV-ACLF） patients. Methods Totally 43 HBV-ACLF patients （HBV-ACLF group） and 46 patients with chronic hepatitis B （CHB） （CHB group）, who were treated in our hospital from Mar. to Oct. 2010, and 20 healthy controls （HC group） were included in the study. ELISA was used to detect the levels of interleukin （IL）-1β, IL-6, IL-10, transforming growth factor （TGF）-β1 and tumor necrosis factor （TNF）-α in the 3 groups. Meanwhile, clinical parameters were investigated. The 43 HBV- ACLF patients were given 3 weeks of follow-up, and the changes of serum cytokine levels were observed dynamically. Results The le- vels of IL-1β, IL-6, IL-10 and TGF-β1 in HBV- ACLF group were higher than those in CHB group and in HC group （P〈0.05）, and the level of TNF-α in HBV-ACLF group was higher than that in HC group （P〈0.05）. In HBV-ACLF group, the level of IL-6 was positively correlated with the levels of TGF-β1 and HBV DNA and model for end-stage liver disease （MELD） score （r=0.403, P〈0.O1; r=0.322, P〈0.05; r=0.338, P〈0.05）; the level of IL-10 was positively correlated with that of CHE （r=0.411, P〈0.01）, and negatively correlated with Na^＋ （r=--0.529, P〈0.01）; the level of TGF-151 was positively correlated with that of CHE （r=0.407, P〈0.01）. The level of IL-1 in medium and late stage HBV-ACLF group was higher than that in early stage group （P〈0.05）. The level of TGF-β1 in medium stage HBV-ACLF group was higher than that in early stage group （P〈0.05）. The levels of IL-6, TGF-β1 and TNF-α in cured or improved group showed a gradually decreasing trend, and the levels of IL-6 and TGF-β1 were lower than those in dead or inefficient group in the group week of follow-up （P〈0.05）. Conclusions HBV-ACLF patients suffered from immune dysfunction of proinflammatory cytokines and anti-inflammatory cytokines. The expression and dynamic changes of cytokine levels have a good clinical significance in the disease progression and prognosis of HBV-ACLF patients.