Abstract：
BACKGROUND: Human epididymis protein 4 (HE4) has been identified as a biomarker for renal fibrosis. This study aimed to evaluate the role of HE4 in the diagnosis and determination of disease severity and hepatic fibrosis in autoimmune hepatitis (AIH).
METHODS: Serum HE4 levels were determined via electrochemiluminescence immunoassays in 60 healthy controls and 109 AIH patients (43 without liver cirrhosis and 66 with liver cirrhosis). Liver biopsy was performed on 56 of 109 enrolled patients. We conducted a 5-year follow-up survey of 53 enrolled patients. All continuous variables were reported as median (25th-75th percentile).
RESULTS: Serum HE4 levels were significantly elevated in autoimmune hepatitis with liver cirrhosis (AIH-LC) patients compared with AIH patients and healthy controls [98.60 (74.15-139.08) vs 73.50 (59.88-82.00) vs 48.75 (43.38-52.93) pmol/L, p = 0.004]. The serum HE4 levels showed a positive correlation with the METAVIR scoring system in patients with liver biopsy (r = 0.711, p < 0.001). Serum HE4 levels were significantly elevated in Child-Pugh class C patients compared with Child-Pugh class B patients and Child-Pugh class A patients [106.50 (83.46-151.25) vs 110.00 (73.83-166.75) vs 77.03 (72.35-83.33) pmol/L, p = 0.006]. The diagnostic sensitivity and specificity of serum HE4 for evaluating liver cirrhosis were 69.7 % and 79.07 %, respectively, with a cutoff value of 82.34 pmol/L in enrolled patients. The logistic regression analysis showed that high levels of HE4 (≥82.34 pmol/L) were associated with AIH-LC (OR = 8.751, 95 % CI = 1.412-54.225, p = 0.020). The Kaplan-Meier curves demonstrated that high levels of serum HE4 (≥82.34 pmol/L) were associated with poor outcome (log-rank p = 0.037, HR = 0.372, 95 % CI = 0.146-0.946).
CONCLUSIONS: Serum HE4 levels were found to be elevated in AIH-LC patients and exhibited a strong correlation with the severity of hepatic fibrosis, thus supporting their potential clinical value as a novel biomarker of disease severity and hepatic fibrosis in AIH.
METHODS: Serum HE4 levels were determined via electrochemiluminescence immunoassays in 60 healthy controls and 109 AIH patients (43 without liver cirrhosis and 66 with liver cirrhosis). Liver biopsy was performed on 56 of 109 enrolled patients. We conducted a 5-year follow-up survey of 53 enrolled patients. All continuous variables were reported as median (25th-75th percentile).
RESULTS: Serum HE4 levels were significantly elevated in autoimmune hepatitis with liver cirrhosis (AIH-LC) patients compared with AIH patients and healthy controls [98.60 (74.15-139.08) vs 73.50 (59.88-82.00) vs 48.75 (43.38-52.93) pmol/L, p = 0.004]. The serum HE4 levels showed a positive correlation with the METAVIR scoring system in patients with liver biopsy (r = 0.711, p < 0.001). Serum HE4 levels were significantly elevated in Child-Pugh class C patients compared with Child-Pugh class B patients and Child-Pugh class A patients [106.50 (83.46-151.25) vs 110.00 (73.83-166.75) vs 77.03 (72.35-83.33) pmol/L, p = 0.006]. The diagnostic sensitivity and specificity of serum HE4 for evaluating liver cirrhosis were 69.7 % and 79.07 %, respectively, with a cutoff value of 82.34 pmol/L in enrolled patients. The logistic regression analysis showed that high levels of HE4 (≥82.34 pmol/L) were associated with AIH-LC (OR = 8.751, 95 % CI = 1.412-54.225, p = 0.020). The Kaplan-Meier curves demonstrated that high levels of serum HE4 (≥82.34 pmol/L) were associated with poor outcome (log-rank p = 0.037, HR = 0.372, 95 % CI = 0.146-0.946).
CONCLUSIONS: Serum HE4 levels were found to be elevated in AIH-LC patients and exhibited a strong correlation with the severity of hepatic fibrosis, thus supporting their potential clinical value as a novel biomarker of disease severity and hepatic fibrosis in AIH.
摘要：
背景：人附睾蛋白4（HE4）已被鉴定为肾纤维化的生物标志物。本研究旨在评估HE4在诊断和确定自身免疫性肝炎（AIH）疾病严重程度和肝纤维化中的作用。
方法：采用电化学发光免疫测定法测定60例健康对照组和109例AIH患者（43例无肝硬化，66例有肝硬化）的血清HE4水平。109例入选患者中有56例进行了肝活检。我们对53名入选患者进行了5年的随访调查。所有连续变量均报告为中位数（第25-75百分位数）。
结果：与AIH患者和健康对照组相比，AIH-LC患者的血清HE4水平显着升高[98.60（74.15-139.08）vs73.50（59.88-82.00）vs48.75（43.38-52.93）pmol/L，p=0.004]。肝活检患者血清HE4水平与METAVIR评分系统呈正相关(r=0.711,p<0.001)。与Child-PughB级患者和Child-PughA级患者相比，Child-PughC级患者的血清HE4水平显着升高[106.50（83.46-151.25）vs110.00（73.83-166.75）vs77.03（72.35-83.33）pmol/L，p=0.006]。血清HE4对肝硬化的诊断敏感性和特异性分别为69.7%和79.07%,分别,纳入患者的截止值为82.34pmol/L。Logistic回归分析显示,HE4水平升高(≥82.34pmol/L)与AIH-LC相关(OR=8.751,95%CI=1.412~54.225,p=0.020)。Kaplan-Meier曲线表明，高水平的血清HE4（≥82.34pmol/L）与不良预后相关（log-rankp=0.037，HR=0.372，95％CI=0.146-0.946）。
结论：AIH-LC患者血清HE4水平升高，与肝纤维化严重程度密切相关，因此支持其作为AIH疾病严重程度和肝纤维化的新型生物标志物的潜在临床价值。
方法：采用电化学发光免疫测定法测定60例健康对照组和109例AIH患者（43例无肝硬化，66例有肝硬化）的血清HE4水平。109例入选患者中有56例进行了肝活检。我们对53名入选患者进行了5年的随访调查。所有连续变量均报告为中位数（第25-75百分位数）。
结果：与AIH患者和健康对照组相比，AIH-LC患者的血清HE4水平显着升高[98.60（74.15-139.08）vs73.50（59.88-82.00）vs48.75（43.38-52.93）pmol/L，p=0.004]。肝活检患者血清HE4水平与METAVIR评分系统呈正相关(r=0.711,p<0.001)。与Child-PughB级患者和Child-PughA级患者相比，Child-PughC级患者的血清HE4水平显着升高[106.50（83.46-151.25）vs110.00（73.83-166.75）vs77.03（72.35-83.33）pmol/L，p=0.006]。血清HE4对肝硬化的诊断敏感性和特异性分别为69.7%和79.07%,分别,纳入患者的截止值为82.34pmol/L。Logistic回归分析显示,HE4水平升高(≥82.34pmol/L)与AIH-LC相关(OR=8.751,95%CI=1.412~54.225,p=0.020)。Kaplan-Meier曲线表明，高水平的血清HE4（≥82.34pmol/L）与不良预后相关（log-rankp=0.037，HR=0.372，95％CI=0.146-0.946）。
结论：AIH-LC患者血清HE4水平升高，与肝纤维化严重程度密切相关，因此支持其作为AIH疾病严重程度和肝纤维化的新型生物标志物的潜在临床价值。
