准确评估和追踪特异性肝损伤及其进程仍然是当前生物标志物研究中的一大挑战。本研究建立了一种回顾追溯验证方法，用以表征α-萘异硫氰酸酯（ANIT）诱导的特异性肝脏胆管损伤后血清标志物与组织标志物之间的互动关系。研究发现羧酸酯酶1（CES1）作为肝内标志物和二肽基肽酶4（DPP-IV）作为肝外标志物可反映肝脏损伤的不同病理生理状态。CES1 和DPP-IV 水平可甄别肝损伤本身和炎症损伤之间的差异。相比之下，常规血清学标志物碱性磷酸酶（ALP）、丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）在ANIT诱导损伤后血清和组织水平同时升高，胆汁中胆汁酸水平下降，血清中胆汁酸水平升高，肝内组织中胆汁酸水平升高。尽管血清与组织中γ-谷氨酰基转肽酶（γ-GT）升降水平的变化方向相反，但其持续时间远短于CES1，并迅速恢复到正常水平。在上述生物标志物中，只有CES1 能够明确排除炎症干扰下的肝细胞损伤。CES1 还能准确评估熊去氧胆酸（UDCA；单成分药物）和清肺排毒汤（QFPDD；多组分药物）的抗胆汁淤积作用。研究发现QFPDD和UDCA均能减轻ANIT 诱导的肝损伤。UDCA在促进胆汁排泄方面的效果更强，但其抗损伤和抗炎作用相对较弱，而QFPDD在阻断肝脏炎症和修复肝损伤方面更有效。本文数据强调了联合使用CES1（作为肝内肝损伤标志物）和DPP-IV（作为肝外炎症作用标志物）可准确评估和追踪特异性肝损伤，并可区分肝损伤和炎症性肝损伤的差异。

Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research. Here, we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct cells caused by a-naphthyl isothiocyanate (ANIT). We found that carboxylesterase 1 (CES1), as an intrahepatic marker, and dipeptidyl peptidase 4 (DPP-IV), as an extrahepatic marker, can reflect the different pathophysiologies of liver injury. Levels of CES1 and DPP-IV can be used to identify liver damage itself and the inflammatory state, respectively. While the levels of the conventional serological biomarkers alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were all concomitantly elevated in serum and tissues after ANIT-induced injury, the levels of bile acids decreased in bile, increased in serum, and ascended in intrahepatic tissue. Although the level of γ-glutamyl transpeptidase (γ-GT) changed in an opposite direction, the duration was much shorter than that of CES1 and was quickly restored to normal levels. Therefore, among the abovementioned biomarkers, only CES1 made it possible to specifically determine whether the liver cells were destroyed or damaged without interference from inflammation. CES1 also enabled accurate assessment of the anti-cholestasis effects of ursodeoxycholic acid (UDCA; single component) and Qing Fei Pai Du Decoction (QFPDD; multicomponent). We found that both QFPDD and UDCA attenuated ANIT-induced liver damage. UDCA was more potent in promoting bile excretion but showed relatively weaker anti-injury and antiinflammatory effects than QFPDD, whereas QFPDD was more effective in blocking liver inflammation and repairing liver damage. Our data highlights the potential of the combined use of CES1 (as an intrahepatic marker of liver damage) and DPP-IV (as an extrahepatic marker of inflammation) for the accurate evaluation and tracking of liver-specific injury–an application that allows for the differentiation of liver damage and inflammatory liver injury.