Abstract：
OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a highly prevalent liver disease that lacks targeted therapeutic drugs and non-invasive diagnostic methods. Increasing evidence demonstrated that aberrant expression of leucine aminopeptidase 3 (LAP3) is involved in NASH. Herein, we aimed to investigate whether LAP3 can be a promising serum biomarker for NASH diagnosis.
METHODS: Liver tissues and serum from NASH rats, serum from NASH patients, and liver biopsies from chronic hepatitis B (CHB) patients combined with NASH (CHB+NASH) were obtained to evaluate the LAP3 level. Correlation analysis was conducted to evaluate the association between LAP3 expression and clinical indexes in CHB patients and CHB+NASH patients. ROC curve analysis of LAP3 in the serum and liver was applied to assess whether LAP3 can be a promising biomarker for NASH diagnosis.
RESULTS: LAP3 was significantly upregulated in serum and hepatocytes of NASH rats and patients with NASH. Correlation analysis revealed that LAP3 in the liver of CHB patients and CHB+NASH patients showed a strong positive correlation with lipidome indicators total cholesterol (TC) and triglyceride (TG), and liver fibrosis indicator hyaluronic acid (HA), which showed a negative correlation with the international normalized ratio of prothrombin coagulation (INR) and liver injury indicator aspartate aminotransferase (AST). For NASH, the diagnostic accuracy of ALT > LAP3 > AST, the sensitivity LAP3 (0.87) > ALT (0.5957) > AST (0.2941), the specificity AST (0.975) > ALT (0.9) > LAP3 (0.5).
CONCLUSIONS: Our data urge that LAP3 can serve as a promising serum biomarker candidate for NASH diagnosis.
METHODS: Liver tissues and serum from NASH rats, serum from NASH patients, and liver biopsies from chronic hepatitis B (CHB) patients combined with NASH (CHB+NASH) were obtained to evaluate the LAP3 level. Correlation analysis was conducted to evaluate the association between LAP3 expression and clinical indexes in CHB patients and CHB+NASH patients. ROC curve analysis of LAP3 in the serum and liver was applied to assess whether LAP3 can be a promising biomarker for NASH diagnosis.
RESULTS: LAP3 was significantly upregulated in serum and hepatocytes of NASH rats and patients with NASH. Correlation analysis revealed that LAP3 in the liver of CHB patients and CHB+NASH patients showed a strong positive correlation with lipidome indicators total cholesterol (TC) and triglyceride (TG), and liver fibrosis indicator hyaluronic acid (HA), which showed a negative correlation with the international normalized ratio of prothrombin coagulation (INR) and liver injury indicator aspartate aminotransferase (AST). For NASH, the diagnostic accuracy of ALT > LAP3 > AST, the sensitivity LAP3 (0.87) > ALT (0.5957) > AST (0.2941), the specificity AST (0.975) > ALT (0.9) > LAP3 (0.5).
CONCLUSIONS: Our data urge that LAP3 can serve as a promising serum biomarker candidate for NASH diagnosis.
摘要：
目的：非酒精性脂肪性肝炎（NASH）是一种高度流行的肝病，缺乏靶向治疗药物和非侵入性诊断方法。越来越多的证据表明，亮氨酸氨基肽酶3（LAP3）的异常表达与NASH有关。在这里，我们的目的是研究LAP3是否可以成为NASH诊断的有前景的血清生物标志物.
方法：NASH大鼠肝组织和血清，来自NASH患者的血清，和肝活检从慢性乙型肝炎（CHB）患者合并NASH（CHB+NASH），以评估LAP3水平。对CHB患者和CHB+NASH患者LAP3表达与临床指标的相关性进行相关性分析。应用血清和肝脏中LAP3的ROC曲线分析来评估LAP3是否可以是用于NASH诊断的有希望的生物标志物。
结果：LAP3在NASH大鼠和NASH患者的血清和肝细胞中显著上调。相关性分析显示,CHB患者和CHB+NASH患者肝脏中LAP3与脂类指标总胆固醇(TC)、甘油三酯(TG)呈强正相关,和肝纤维化指标透明质酸（HA），与凝血酶原凝血指标（INR）和肝损伤指标天门冬氨酸氨基转移酶（AST）的国际标准化比值呈负相关。对于NASH，ALT>LAP3>AST的诊断准确性，灵敏度LAP3(0.87)>ALT(0.5957)>AST(0.2941)，特异性AST(0.975)>ALT(0.9)>LAP3(0.5)。
结论：我们的数据敦促LAP3可以作为NASH诊断的有希望的血清生物标志物候选物。
方法：NASH大鼠肝组织和血清，来自NASH患者的血清，和肝活检从慢性乙型肝炎（CHB）患者合并NASH（CHB+NASH），以评估LAP3水平。对CHB患者和CHB+NASH患者LAP3表达与临床指标的相关性进行相关性分析。应用血清和肝脏中LAP3的ROC曲线分析来评估LAP3是否可以是用于NASH诊断的有希望的生物标志物。
结果：LAP3在NASH大鼠和NASH患者的血清和肝细胞中显著上调。相关性分析显示,CHB患者和CHB+NASH患者肝脏中LAP3与脂类指标总胆固醇(TC)、甘油三酯(TG)呈强正相关,和肝纤维化指标透明质酸（HA），与凝血酶原凝血指标（INR）和肝损伤指标天门冬氨酸氨基转移酶（AST）的国际标准化比值呈负相关。对于NASH，ALT>LAP3>AST的诊断准确性，灵敏度LAP3(0.87)>ALT(0.5957)>AST(0.2941)，特异性AST(0.975)>ALT(0.9)>LAP3(0.5)。
结论：我们的数据敦促LAP3可以作为NASH诊断的有希望的血清生物标志物候选物。
