摘要
目的探讨血清高尔基体蛋白73(GP73)动态变化对乙型肝炎肝纤维化逆转的预测作用及其炎症影响因素。方法采用回顾性研究,选取自2014年9月—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且完成2次肝活组织检查的乙型肝炎肝纤维化患者278例。分析血清GP73水平与纤维化分期(Ishak)、炎症分级(HAI)的相关性;并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下降≥1分)与未逆转组(Ishak评分不变或上升)、炎症改善组(ΔHAI≤-2)与未改善组(ΔHAI>-2);评估治疗前后GP73横断面值及其变化值(ΔGP73)对肝纤维化消退的预测效能及肝脏炎症对该预测作用的影响。通过受试者操作特征曲线探讨血清ΔGP73联合肝硬度变化值(ΔLSM)对乙型肝炎肝纤维化逆转的预测价值。计量资料组间数据比较采用单因素方差分析、治疗前后数据采用配对t检验或秩和检验;计数资料采用χ^(2)检验比较组间数据差异;相关性分析采用Spearman及Pearson相关法。结果肝硬化组血清GP73水平高于无显著纤维化组(P<0.01),中、重度炎症患者GP73水平高于轻度组(P值均<0.05)。治疗前血清GP73水平与纤维化期(r=0.248)、炎症分级(r=0.318)、丙氨酸转氨酶水平(r=0.311)均呈正相关(P值均<0.01)。治疗后GP73水平预测纤维化逆转的受试者操作特征曲线下面积(AUROC)为0.633[95%置信区间(CI):0.573~0.689,灵敏度为62.68%,特异度为59.56%]。GP73在肝纤维化逆转组(n=142)中的下降程度明显大于未逆转组(n=136)[-39.22(-85.08,-14.31)ng/mL比-30.06(-61.29,-5.84)ng/mL,P<0.01]。ΔGP73也与肝脏炎症变化相关(AUROC=0.634,95%CI:0.574~0.690,灵敏度为51.64%,特异度为69.87%),而血清ALT复常后GP73预测纤维化逆转效能有所提升(AUROC:0.651比基线的0.522)。ΔGP73联合ΔLSM可将预测效能AUROC从单一指标的0.609(ΔGP73)或0.656(ΔLSM)提升至0.800(95%CI:0.662~0.899),特异度从72.22%、30.56%提高至86.11%。结论血清GP73水平与肝纤维化及炎症程度呈正相关;治疗后血清GP73水平及其ΔGP73可预测纤维化逆转,肝脏炎症是重要影响因素;ΔGP73联合ΔLSM可显著优化肝纤维化逆转的评估效能。
ObjectiveTo 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.MethodsTwo 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 serumΔGP73 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.Theχ^(2) test was used to compare the differences between the groups of enumeration data.Spearman and Pearson correlation methods were used for correlation analysis.ResultsThe serum GP73 level was higher in the cirrhosis group than that in the group without significant fibrosis(P<0.01).The GP73 level was higher in patients with moderate and severe inflammation than that in the mild group(P<0.05).Pre-treatment serum GP73 was positively correlated with fibrosis stage(r=0.248),inflammation grade(r=0.318),and alanine aminotransferase level(r=0.203)(P<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%CI:0.573-0.689,sensitivity 62.68%,and specificity 59.56%).The decrease inΔGP73 was significantly higher in the liver fibrosis reversal group(n=142)than that in the non-reversal group(n=136)[-39.22(-85.08,-14.31)ng/mL vs.-30.06(-61.29,-5.84)ng/mL,P<0.01].ΔGP73 was also associated with liver inflammation changes(AUROC=0.634,95%CI: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 withΔLSM had improved the AUROC predictive effectiveness from single indicators of 0.609(ΔGP73)and 0.656(ΔLSM)to 0.800(95%CI:0.662-0.899),with specificity increasing from 72.22%to 86.11%.ConclusionSerum GP73 level is positively correlated with the degree of liver fibrosis and inflammation.Serum GP73 levels andΔGP73 can predict the reversal of fibrosis,with liver inflammation being an important influencing factor following treatment.ΔGP73 combined withΔLSM can significantly optimize the evaluation efficiency of liver fibrosis reversal.
作者
范海纳
马杨青
孙鑫
黄恺
邢枫
刘成海
Fan Haina;Ma Yangqing;Sun Xin;Huang Kai;Xing Feng;Liu Chenghai(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)
出处
《中华肝脏病杂志》
北大核心
2025年第8期772-780,共9页
Chinese Journal of Hepatology
基金
国家自然科学基金(81730109,82274305)
国家科技重大专项(2018ZX10302204)
上海市临床重点专科建设项目(shslczdzk01201)。
