Leucine aminopeptidase 3:a promising serum biomarker candidate for nonalcoholic steatohepatitis diagnosis

Background & aims: 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).

Conclusion: Our data urge that LAP3 can serve as a promising serum biomarker candidate for NASH diagnosis.

ALT; LAP3; NASH; ROC analysis; Serum biomarker.