白细胞介素22对晚期肝硬化患者预后预测价值研究

Prognostic value of Interleukin-22 in liver cirrhosis patients

目的探讨血清IL-22含量与晚期肝硬化患者发病率和死亡率的关系。方法本研究对120例肝硬化患者和40名健康受试者的IL-22的水平进行了研究。结果在本研究过程中71%的肝硬化患者有并发症发生。平均随访时间为(196±165)d,在此期间共有23%患者死亡。74%的肝硬化患者及10%健康受试者中可以检测到IL-22(P<0.001)。IL-22含量升高与腹水(P=0.006)、肝肾综合征(P<0.0001)、自发性细菌性腹膜炎(P=0.001)相关。IL-22(>18pg/mL,n=57)含量高的患者与一般水平(≤18 pg/mL)患者相比,存活率显著降低(321 d与526 d,P=0.003)。降低存活率的其他因素包括高CRP、血清肌酐升高、肝脏并发症及终末期肝病(MELD)的模型评分≥20和年龄。多变量Cox比例风险分析表明IL-22水平升高是存活率降低的独立预测因子。结论肝硬化患者体内的IL-22全身水平升高是独立于年龄、肝脏并发症、C反应蛋白、肌酐和MELD评分的预测因素。因此,全身白细胞介素22的上升与晚期肝硬化预后相关。

【Objective】To investigate whether plasma Interleukin-22 is an independent predictor of mortality in liver cirrhosis patients. 【Methods】This is a prospective cohort study including 120 liver cirrhosis patients and 40healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications.【Results】A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 ± 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors（P〈0.001）. Elevated levels of IL-22 were associated with ascites（P =0.006）, hepato-renal syndrome（P〈0.0001）, and spontaneous bacterial peritonitis（P =0.001）. Patients with elevated IL-22（〉18 pg/mL, n=57） showed significantly reduced survival compared to patients with regular（≤18 pg/mL） levels of IL-22（321 days versus 526 days, P =0.003）. Other factors associated with reduced overall survival were high CRP（≥2.9 mg/dL, P =0.005, hazard ratio（HR） 0.314, confidence interval（CI）（0.141-0.702）, elevated serum creatinine（P=0.05, HR 0.453,CI（0.203-1.012）, presence of liver-related complications（P=0.028, HR 0.258, CI（0.077 to 0.862））, model of end stage liver disease（MELD） score ≥20（P =0.017, HR 0.364, CI（0.159-0.835） and age（P =0.011, HR 0.955, CI（0.922-0.989）. Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival（P =0.007, HR 0.218, CI（0.072-0.662））.【Conclusions】In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis.