自身免疫性肝炎患者血清HE4水平变化及其对疾病严重程度和肝纤维化的影响

肝脏 ›› 2026, Vol. 31 ›› Issue (1): 68-70.

自身免疫性肝炎患者血清HE4水平变化及其对疾病严重程度和肝纤维化的影响

张玲, 程婉茜, 林玲

211100 南京南京同仁医院检验科(张玲,林玲);211100 南京南京中医药大学附属南京医院药学部(南京市第二医院)(程婉茜)

收稿日期:2025-06-17 出版日期:2026-01-31 发布日期:2026-03-30
通讯作者: 林玲,Email:linl2@njtrh.org
基金资助:
南京市卫生科技发展专项资金项目重点项目(ZKX2202)

Serum human epididymis protein 4 levels in patients with autoimmune hepatitis and its association with disease severity and liver fibrosis

ZHANG Ling¹, CHENG Wan-qian², LIN Ling¹

1. Department of Laboratory Medicine, Nanjing Tongren Hospital, Nanjing 211100,China;
2. Department of Pharmacy,Nanjing University of Traditional Chinese Medicine Affiliated Nanjing Hospital (Nanjing Second Hospital),Nanjing 211100,China

Received:2025-06-17 Online:2026-01-31 Published:2026-03-30
Contact: LIN Ling,Email:linl2@njtrh.org

摘要/Abstract

摘要： 目的探讨自身免疫性肝炎(AIH)患者血清人附睾蛋白4(HE4)水平的变化特点,并分析其与疾病严重程度、肝纤维化程度的相关性,评估HE4在AIH诊治过程中的潜在价值,为AIH的个体化治疗和病情监测提供新的思路和理论依据。方法纳入2020年6月至2024年12月于我院就诊并符合诊断标准的AIH患者77例,比较不同疾病严重程度、肝组织炎症活动度分级以及肝纤维化分期AIH患者HE4水平表达情况,并评估HE4水平预测AIH患者病情严重程度、肝组织炎症和肝纤维化情况的效能。结果根据病情严重程度分级,重度AIH患者血清ALT、AST、TBil及HE4水平为137(108,211)U/L、146(112,194)U/L、91.5(68.0,117.4)μmol/L及78.6(54.5,90.2)pmol/L,显著高于轻中度患者[77(55,91)U/L、65(50,85)U/L、27.7(19.8,36.5)μmol/L及50.7(36.6,68.0)pmol/L,P<0.05],而Alb水平为(36.4±1.8)g/L,显著低于轻中度患者[(41.0±2.6)g/L,P<0.05]。显著肝组织炎症分级或肝纤维化分期AIH患者的HE4水平显著高于较轻组织学炎症或肝纤维化患者,差异有统计学意义(P<0.05)。HE4预测AIH患者不同病情严重程度、肝组织炎症分级以及肝纤维化分期的效能较高,诊断AUC值均超过0.80。结论血清HE4水平在AIH患者中显著升高,且其水平与疾病严重程度、肝组织炎症活动度及肝纤维化程度密切相关。HE4可作为一种潜在的非侵袭性生物标志物,用于辅助评估AIH患者的疾病活动性及肝组织损伤程度,具有良好的诊断效能和临床应用前景。

关键词: 自身免疫性肝炎, 人附睾蛋白4, 肝组织炎症活动度, 肝纤维化

Abstract: Objective To investigate the changes in serum human epididymis protein 4 (HE4) levels in patients with autoimmune hepatitis (AIH), and to analyze the correlation between HE4 levels and disease severity as well as liver fibrosis stage. This study aims to evaluate the potential clinical value of HE4 in the diagnosis and management of AIH, thereby providing new insights and a theoretical basis for individualized treatment and disease monitoring in AIH. Methods A total of 77 AIH patients who were diagnosed and treated at our hospital between June 2020 and December 2024 were enrolled. Serum HE4 levels were compared among patients with different disease severity, histological inflammation grades, and fibrosis stages. The diagnostic performance of HE4 for predicting disease severity, hepatic inflammation, and liver fibrosis was assessed. Results According to severity classification, serum levels of ALT, AST, TBil, and HE4 in severe AIH patients were 137 (108, 211) U/L, 146 (112, 194) U/L, 91.5 (68.0, 117.4) μmol/L, and 78.6 (54.5, 90.2) pmol/L, respectively, significantly higher than those in mild-to-moderate patients [77 (55, 91) U/L, 65 (50, 85) U/L, 27.7 (19.8, 36.5) μmol/L, and 50.7 (36.6, 68.0) pmol/L, P<0.05]. Conversely, the Alb level was (36.4±1.8) g/L, significantly lower than that in mild-to-moderate patients [(41.0±2.6) g/L, P<0.05]. Patients with a higher histological inflammation grade or liver fibrosis stage had significantly higher HE4 levels compared to those with milder grades or stages, with statistically significant differences (P<0.05). HE4 demonstrated high efficacy in predicting different severity levels, histological inflammation grades, and liver fibrosis stages in AIH patients, with diagnostic AUC values all exceeding 0.80. Conclusion Serum HE4 levels are significantly elevated in AIH patients and closely associated with disease severity, histological inflammatory activity, and the extent of liver fibrosis. HE4 may serve as a potential non-invasive biomarker to aid in the assessment of disease activity and liver tissue injury in AIH, showing promising diagnostic value and clinical application potential.

Key words: Autoimmune hepatitis, Human epididymis protein 4, Histological inflammatory activity, Liver fibrosis

张玲, 程婉茜, 林玲. 自身免疫性肝炎患者血清HE4水平变化及其对疾病严重程度和肝纤维化的影响[J]. 肝脏, 2026, 31(1): 68-70.

ZHANG Ling, CHENG Wan-qian, LIN Ling. Serum human epididymis protein 4 levels in patients with autoimmune hepatitis and its association with disease severity and liver fibrosis[J]. Chinese Hepatolgy, 2026, 31(1): 68-70.

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参考文献

[1] Guo D, Li X, Wei S, et al. Prescription regularity and pharmacodynamics mechanism of traditional Chinese medicine in autoimmune hepatitis: a data mining and network pharmacology study[J]. Medicine (Baltimore), 2024, 103(52):e41146.
[2] Wei Q, Li W, He S, et al. An exploratory machine learning model for predicting advanced liver fibrosis in autoimmune hepatitis patients: a preliminary study[J]. Ann Hepatol, 2025, 30(1):101754.
[3] Olivas I, Arvaniti P, Gabeta S, et al. Liver stiffness measurement predicts clinical outcomes in autoimmune hepatitis[J]. JHEP Rep, 2024, 6(11):101213.
[4] Kim N I, Park M H, Lee J S. Assessment of human epididymis protein 4 expression in breast ductal carcinoma in situ[J]. Diagnostics (Basel), 2025, 15(9):1058.
[5] Zare M E, Nasir Kansestani A, Wu X, et al. Serum human epididymis protein-4 outperforms conventional biomarkers in the early detection of non-small cell lung cancer[J]. iScience, 2024, 27(11):111211.
[6] Mohamed N F, Ali Behairy O G, Sadek El Defrawy M, et al. Evaluation of serum human epididymis protein 4 in children with chronic liver diseases[J]. Scand J Clin Lab Invest, 2024, 84(7-8):515-520.
[7] Hou Y, Li F, Chen J, et al. Clinical significance of serum human epididymis protein 4 in liver fibrosis: an experimental study[J]. Medicine (Baltimore), 2020, 99(48):e23428.
[8] Lohse A W, Sebode M, Bhathal P S, et al. Consensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group: results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology: results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology[J]. Liver Int, 2022, 42(5):1058-1069.
[9] Laschtowitz A, Zachou K, Lygoura V, et al. Histological activity despite normal ALT and IgG serum levels in patients with autoimmune hepatitis and cirrhosis[J]. JHEP Rep, 2021, 3(4):100321.
[10] Shi J, Fu J, He C, et al. Diagnostic and prognostic biomarkers in autoimmune hepatitis-associated cirrhosis: insights into TBil, CD38, IL-22, TSP-1, GAL-3, and Cyc-C[J]. Front Med (Lausanne), 2025, 12:1564107.
[11] Li R, Xu J, Wu M, et al. Circulating CD4⁺ treg, CD8⁺ treg, and CD3⁺ γδ T cell subpopulations in ovarian cancer[J]. Medicina (Kaunas), 2023, 59(2):205.
[12] Wu S, Yang Z, Zhou J, et al. Systematic review: diagnostic accuracy of non-invasive tests for staging liver fibrosis in autoimmune hepatitis[J]. Hepatol Int, 2019, 13(1):91-101.
[13] Nawalerspanya S, Tantipisit J, Assawasuwannakit S, et al. Non-invasive serum biomarkers for the diagnosis of cirrhosis in patients with autoimmune hepatitis (AIH) and AIH-primary biliary cholangitis overlap syndrome (AIH-PBC): red cell distribution width to platelet ratio (RPR) yielded the most promising result[J]. Diagnostics (Basel), 2024, 14(3):265.
[14] Zachou K, Lygoura V, Arvaniti P, et al. FibroMeter scores for the assessment of liver fibrosis in patients with autoimmune liver diseases[J]. Ann Hepatol, 2021, 22:100285.
[15] Dong B, Chen Y, Lyu G, et al. Aspartate aminotransferase to platelet ratio index and fibrosis-4 index for detecting liver fibrosis in patients with autoimmune hepatitis:a meta-analysis[J]. Front Immunol, 2022, 13:892454.