Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4

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 α-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; multi-component). 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 anti-inflammatory 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.