Fan H N, Ma Y Q, Sun X, Huang K, Xing F, Liu C H
Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China Shanghai Clinical Key Laboratory of Traditional Chinese Medicine, Shanghai 201203, China.
Zhonghua Gan Zang Bing Za Zhi. 2025 Aug 20;33(8):772-780. doi: 10.3760/cma.j.cn501113-20240419-00212.
To explore the predictive role of dynamic changes in serum Golgi protein 73 (GP73) and its inflammatory influencing factors on the reversal of hepatitis B virus-related liver fibrosis. Two hundred and seventy-eight patients with hepatitis B virus-related liver fibrosis who received entecavir or combined Fuzheng Huayu tablets treatment and completed two liver biopsies (biopsy) in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September 2014 to July 2019 were selected. The correlation between serum GP73 level and fibrosis stage (Ishak) and inflammation grade (HAI) was analyzed. The patients were divided into a fibrosis reversal group (Ishak decreased≥1 point) and a non-reversal group (Ishak score remained unchanged or increased), and an inflammation improvement group (ΔHAI≤-2) and a non-improvement group (ΔHAI>-2) according to the pathological changes of liver tissue before and after treatment. The cross-sectional value of GP73, its change value (ΔGP73), and the role of inflammatory influencing factors on the liver before and after treatment were evaluated for their predictive efficacy regarding liver fibrosis regression. The receiver operating characteristic curve was used to explore the predictive value of serum ΔGP73 combined with liver stiffness change value (ΔLSM) for the reversal of hepatitis B virus-related liver fibrosis. One-way analysis of variance was used to compare the data between the groups of quantitative data, and a paired t-test or rank sum test was used for the data before and after treatment. The test was used to compare the differences between the groups of enumeration data. Spearman and Pearson correlation methods were used for correlation analysis. The serum GP73 level was higher in the cirrhosis group than that in the group without significant fibrosis (<0.01). The GP73 level was higher in patients with moderate and severe inflammation than that in the mild group (<0.05). Pre-treatment serum GP73 was positively correlated with fibrosis stage (=0.248), inflammation grade (=0.318), and alanine aminotransferase level (=0.203) (<0.01). The area under the receiver operating characteristic curve (AUROC) for the predictive ability of post-treatment GP73 levels in the fibrosis reversal was 0.633 (95%: 0.573-0.689, sensitivity 62.68%, and specificity 59.56%). The decrease in ΔGP73 was significantly higher in the liver fibrosis reversal group (=142) than that in the non-reversal group (=136) [-39.22(-85.08,-14.31) ng/mL . -30.06(-61.29,-5.84) ng/mL, <0.01]. ΔGP73 was also associated with liver inflammation changes (AUROC=0.634, 95%: 0.574-0.690, sensitivity of 51.64%, specificity of 69.87%). Additionally, the predictive effectiveness of GP73 for fibrosis reversal improved after normalization of serum ALT (AUROC: 0.651 vs. 0.522 at baseline). ΔGP73 combined with ΔLSM had improved the AUROC predictive effectiveness from single indicators of 0.609 (ΔGP73) and 0.656 (ΔLSM) to 0.800 (95%: 0.662-0.899), with specificity increasing from 72.22% to 86.11%. Serum GP73 level is positively correlated with the degree of liver fibrosis and inflammation. Serum GP73 levels and ΔGP73 can predict the reversal of fibrosis, with liver inflammation being an important influencing factor following treatment. ΔGP73 combined with ΔLSM can significantly optimize the evaluation efficiency of liver fibrosis reversal.
探讨血清高尔基体蛋白73(GP73)动态变化及其炎症影响因素对乙型肝炎病毒相关性肝纤维化逆转的预测作用。选取2014年9月至2019年7月在上海中医药大学附属曙光医院接受恩替卡韦或联合扶正化瘀片治疗并完成两次肝活检的278例乙型肝炎病毒相关性肝纤维化患者。分析血清GP73水平与纤维化分期(Ishak)及炎症分级(HAI)的相关性。根据治疗前后肝组织病理变化将患者分为纤维化逆转组(Ishak降低≥1分)和非逆转组(Ishak评分不变或升高),以及炎症改善组(ΔHAI≤ -2)和非改善组(ΔHAI > -2)。评估GP73的横断面值、其变化值(ΔGP73)以及炎症影响因素在治疗前后对肝脏的作用,以预测肝纤维化消退的疗效。采用受试者工作特征曲线探讨血清ΔGP73联合肝脏硬度变化值(ΔLSM)对乙型肝炎病毒相关性肝纤维化逆转的预测价值。采用单因素方差分析比较定量数据组间的数据,采用配对t检验或秩和检验分析治疗前后的数据。采用检验比较计数数据组间的差异。采用Spearman和Pearson相关方法进行相关性分析。肝硬化组血清GP73水平高于无明显纤维化组(<0.01)。中度和重度炎症患者的GP73水平高于轻度组(<0.05)。治疗前血清GP73与纤维化分期(=0.248)、炎症分级(=0.318)及丙氨酸氨基转移酶水平(=0.203)呈正相关(<0.01)。治疗后GP73水平对纤维化逆转的预测能力的受试者工作特征曲线下面积(AUROC)为0.633(95%:0.573 - 0.689,敏感性62.68%,特异性59.56%)。肝纤维化逆转组(=142)的ΔGP73下降幅度显著高于非逆转组(=136)[-39.22(-85.08,-14.31)ng/mL -30.06(-61.29,-5.84)ng/mL,<0.01]。ΔGP73也与肝脏炎症变化相关(AUROC = 0.634,95%:0.574 - 0.690,敏感性51.64%,特异性69.87%)。此外,血清ALT正常化后,GP73对纤维化逆转的预测有效性提高(AUROC:基线时为0.651对0.522)。ΔGP73联合ΔLSM使AUROC预测有效性从单一指标的0.609(ΔGP73)和0.656(ΔLSM)提高到0.800(95%:0.662 - 0.899),特异性从72.22%提高到86.