[Value of constructing a non-invasive diagnostic model based on serum heme oxygenase-1 and glucose regulatory protein 78 for non-alcoholic fatty liver disease]

Zhonghua Gan Zang Bing Za Zhi. 2024 Mar 20;32(3):228-234. doi: 10.3760/cma.j.cn501113-20230830-00079.
[Article in Chinese]

Abstract

Objective: To analyze the clinical application value of serum heme oxygenase (HO)-1expression level in non-alcoholic fatty liver disease (NAFLD) and, based on that, establish a diagnostic model combined with glucose regulatory protein 78 (GRP78) so as to clarify its diagnostic effectiveness and application value. Methods: A total of 210 NAFLD patients diagnosed by abdominal B-ultrasound and liver elastography were included, and at the same time, 170 healthy controls were enrolled. The general clinical data, peripheral blood cell counts, and biochemical indicators of the research subjects were collected. The expression levels of HO-1 and GRP78 were detected using an enzyme-linked immunosorbent assay. Multivariate analysis was used to screen independent risk factors for NAFLD. Visual output was performed through nomogram diagrams, and the diagnostic model was constructed. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the diagnostic effectiveness of NAFLD. Measurement data were analyzed using a t-test or Mann-Whitney U rank sum test to detect data differences between groups. Enumeration data were analyzed using the Fisher's exact probability test or the Pearson χ(2) test. Results: Compared with the healthy control group, the white blood cell count, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase (GTT), fasting blood glucose (Glu), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum HO-1, and GRP78 levels were significantly increased in the NAFLD group patients (P < 0.05). Binary logistic analysis results showed that AST, TG, LDL-C, serum HO-1, and GRP78 were independent risk factors for NAFLD (P < 0.05). A nomogram clinical predictive model HGATL was established using HO-1 (H), GRP78 (G) combined with AST (A), TG (T), and LDL-C (L), with the formula P=-21.469+3.621×HO-1+0.116 ×GRP78+0.674×AST+6.250×TG+4.122 ×LDL-C. The results confirmed that the area under the ROC curve of the HGATL model was 0.965 8, with an optimal cutoff value of 81.69, a sensitivity of 87.06%, a specificity of 92.82%, a P < 0.05, and the diagnostic effectiveness significantly higher than that of a single indicator. The calibration curve and DCA both showed that the model had good diagnostic performance. Conclusion: The HGATL model can be used as a novel, non-invasive diagnosis model for NAFLD and has a positive application value in NAFLD diagnosis and therapeutic effect evaluation. Therefore, it should be explored and promoted in clinical applications.

目的: 分析血清血红素加氧酶(HO)-1表达量对非酒精性脂肪性肝病(NAFLD)的临床应用价值,并以此为基础联合葡萄糖调节蛋白(GRP)78建立诊断模型,明确其诊断NAFLD的效能及应用价值。 方法: 共纳入经腹部B超及肝脏弹性成像技术检测确诊的210例NAFLD患者,同时收集170名健康对照人群。采集研究对象的一般临床资料、外周血细胞计数及生化指标,应用酶联免疫吸附法对HO-1与GRP78表达水平进行检测。采用多因素分析筛选NAFLD的独立危险因素,通过Nomogram图进行可视化输出,并构建诊断模型;采用受试者操作特征曲线(ROC)、校准曲线及决策曲线分析(DCA)评估其诊断NAFLD的效能。计量资料数据采用t检验或Mann-Whitney U秩和检验检测组间数据差异;计数资料采用Fisher精确概率法检验或Pearson χ(2)检验进行分析。 结果: 与健康对照组相比,NAFLD组患者白细胞计数、天冬氨酸转氨酶(AST)、丙氨酸转氨酶、γ-谷氨酰转移酶(GTT)、空腹血糖(Glu)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、血清HO-1、GRP78水平均显著升高(P值均 < 0.05)。二元logistic回归分析结果显示AST、TG、LDL-C、血清HO-1、GRP78为NAFLD患病的独立危险因素(P值均 < 0.05)。以HO-1(H)、GRP78(G)联合AST(A)、TG(T)和LDL-C(L)建立Nomogram临床预测模型HGATL,公式为P = -21.469+3.621×HO-1+0.116×GRP78+0.674×AST+6.250×TG+4.122×LDL-C。结果证实HGATL模型的ROC曲线下面积为0.965 8,最佳截断值为81.69,灵敏度为87.06%,特异度为92.82%,P < 0.05,诊断效能显著高于单一指标。校准曲线及DCA均提示该模型具有较好的诊断效能。 结论: HGATL模型可作为NAFLD无创诊断新模型,在NAFLD的诊断中有积极的应用价值,可在临床应用中探讨推广。.

Keywords: Diagnosis; Fatty liver; Glucose-regulated protein 78; Heme oxygenase-1.

Publication types

  • English Abstract

MeSH terms

  • Cholesterol, LDL
  • Endoplasmic Reticulum Chaperone BiP
  • Glucose
  • Heme Oxygenase-1
  • Humans
  • Non-alcoholic Fatty Liver Disease*
  • Triglycerides

Substances

  • Glucose
  • Cholesterol, LDL
  • Heme Oxygenase-1
  • Endoplasmic Reticulum Chaperone BiP
  • Triglycerides