血清TRAF6、FGF21表达与肝硬化合并上消化道出血患者病情程度及预后的关系OA
The relationship between the expression of serum TRAF6 and FGF21 and the disease severity and prognosis in pa-tients with liver cirrhosis with upper gastrointestinal bleeding
目的 探究血清肿瘤坏死因子受体相关因子 6(TRAF6)、成纤维细胞生长因子 21(FGF21)表达与肝硬化(LC)合并上消化道出血(UGIB)患者病情程度及预后的关系.方法 前瞻性连续纳入 2022 年 6 月—2025 年 6月天津医科大学第二医院消化内科确诊的 LC 合并 UGIB 患者85 例作为 UGIB 组,根据病情程度分为轻度亚组28 例、中度亚组 39 例、重度亚组 18 例,根据随访 6 个月预后分为良好亚组 62 例和不良亚组 23 例;另选取同时期医院健康体检者 85 例作为 NC 组.采用 ELISA 法检测血清 TRAF6、FGF21 水平;Spearman 秩相关分析法评估血清 TRAF6、FGF21 水平与 LC 合并 UGIB 患者病情严重程度的相关性;多因素 Logistic 回归分析 LC 合并 UGIB 患者预后不良的影响因素;ROC 曲线分析血清 TRAF6、FGF21 水平对 LC 合并 UGIB 患者预后的预测效能;采用 DCA 评估模型的临床实用性,并通过 CIC 曲线评价预测模型的临床净收益.结果 UGIB 组血清 TRAF6、FGF21 水平高于 NC 组(t/P=11.557/<0.001、14.069/<0.001);不同病情程度 UGIB 患者血清 TRAF6、FGF21 水平比较,重度亚组>中度亚组>轻度亚组(F/P=18.291/<0.001、21.998/<0.001);LC 合并 UGIB 患者血清 TRAF6、FGF21 水平分别与其病情程度呈正相关(r/P=0.402/<0.001、0.413/<0.001);与良好亚组比较,不良亚组肝功能 Child-Pugh 分级 C 级、病情程度 C 级、24 h 内再出血占比以及血清 TRAF6、FGF21 水平均升高(χ2/P=8.136/0.017、7.360/0.025、4.413/0.036,t/P=7.610/<0.001、7.661/<0.001);病情重度及 TRAF6 高、FGF21 高为 LC 合并 UGIB 患者预后不良的独立危险因素[OR(95%CI)=2.634(1.246~5.569)、2.749(1.313~5.756)、2.347(1.239~4.446)];血清 TRAF6、FGF21 水平单独及二者联合预测 LC 合并UGIB 患者预后不良的 AUC 分别为 0.863、0.852、0.944,二者联合优于其各自单独预测价值(Z/P=2.671/<0.001、2.142/<0.001);DCA 曲线表明,在 0.09~0.89 阈值范围内联合模型临床净收益优于单项指标;CIC 曲线显示,风险概率在 0~0.78 时模型识别的高危人群完全覆盖实际不良结局患者.结论 LC 合并 UGIB 患者血清 TRAF6、FGF21 水平升高,且与病情程度及预后密切相关,二者可能是该疾病潜在治疗靶点.
Objective To investigate the relationship between serum tumor necrosis factor receptor-associated factor 6(TRAF6)and fibroblast growth factor 21(FGF21)levels and disease severity and prognosis in patients with liver cirrhosis complicated by upper gastrointestinal bleeding(UGIB).Methods A total of 85 patients with liver cirrhosis and UGIB were prospectively enrolled as the UGIB group,with further subgrouping based on disease severity and prognosis.Additionally,85 healthy individuals who underwent physical examinations at our hospital during the same period were included as the normal control(NC)group.Spearman rank correlation analysis was used to evaluate the association between serum TRAF6 and FGF21 levels and disease severity.A multivariate logistic regression model was applied to identify factors affecting patient prognosis.ROC curves were used to assess the predictive performance of individual markers and their combination.The clini-cal utility of the combined model was further evaluated using decision curve analysis(DCA),and the clinical net benefit was assessed via the clinical impact curve(CIC).Results Serum TRAF6 and FGF21 levels were significantly higher in the UGIB group than in the NC group(t=11.557,14.069;both P<0.001),and showed an increasing trend with disease severity(F=18.291,21.998;both P<0.001).Serum TRAF6 and FGF21 levels were positively correlated with the severity of UGIB in pa-tients with liver cirrhosis(r=0.402,0.413;both P<0.001).In the poor prognosis subgroup,patients with Child-Pugh class C,severe disease,and rebleeding within 24 hours had significantly higher serum TRAF6 and FGF21 levels compared to those with good prognosis(χ2/t=8.136,7.360,4.413,7.610,7.661;all P<0.05).Disease severity and elevated serum TRAF6 and FGF21 levels were independent risk factors for poor prognosis[OR(95%CI)=2.634(1.246-5.569),2.749(1.313-5.756),2.347(1.239-4.446)].The AUCs of serum TRAF6,FGF21,and their combination for predicting poor prognosis were 0.863,0.852,and 0.944,respectively,with the combined model showing superior predictive value(Z=2.671,2.142;both P<0.001).DCA indicated that the combined model provided better clinical net benefit than individual markers within the threshold range of 0.09-0.89.The CIC curve showed that when the risk probability ranged from 0 to 0.78,the high-risk population identi-fied by the model fully covered the actual patients with poor outcomes.Conclusion Serum TRAF6 and FGF21 levels in pa-tients with liver cirrhosis and UGIB are associated with disease severity and prognosis.These two factors may serve as poten-tial therapeutic targets for this disease.
何荣荣;江勇;齐向娟;金玉青;张颖
300211 天津医科大学第二医院消化内科300211 天津医科大学第二医院消化内科300211 天津医科大学第二医院消化内科300211 天津医科大学第二医院消化内科300211 天津医科大学第二医院消化内科
医药卫生
肝硬化上消化道出血肿瘤坏死因子受体相关因子6成纤维细胞生长因子21病情程度预后
Liver cirrhosisUpper gastrointestinal bleedingTumor necrosis factor receptor-associated factor 6Fi-broblast growth factor 21Disease severityPrognosis
《疑难病杂志》 2026 (9)
1069-1074,6
天津市科技计划项目(25JCLMJC00340) Tianjin Science and Technology Plan Project(25JCLMJC00340)
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