Abstract: Objective To investigate the auxiliary diagnostic value of serum chitinase⁃3⁃like protein 1 (CHI3L1) in hepatitis B virus (HBV)⁃related hepatocellular carcinoma (HCC). Methods A total of 654 patients with HBV⁃related HCC, 408 patients with chronic hepatitis B (CHB), and 551 apparently healthy individuals (AHC) were enrolled. The levels of serum CHI3L1, alpha⁃fetoprotein (AFP), alpha⁃fetoprotein variant L3 (AFP⁃L3), and des⁃γ⁃carboxy prothrombin prothrombin (DCP) were quantified. Receiver operating characteristic (ROC) curves were plotted. The sensitivity, specificity, and area under the curve (AUC) were used to determine the anxiliary diagnostic value of each serum biomarker in identifying HBV⁃related HCC. Results The levels of serum CHI3L1 (156.16 ng/mL), AFP (125.29 ng/mL), AFP⁃L3 (14.96 ng/mL), and DCP (359.75 ng/mL) were significantly elevated in the HCC group compared to the CHB and AHC groups (all P<0.001). In the context of  auxiliary diagnosis for HBV⁃related HCC, early⁃stage HCC, and small HCC using individual biomarkers, AFP yielded the highest AUC among the four biomarkers. Nevertheless, the diagnostic efficacy was significantly improved when AFP combined with AFP⁃L3, DCP, and CHI3L1. For HBV⁃related HCC patients who are AFP⁃negative (<20 ng/mL), the supplementary diagnostic efficacy of the combination of CHI3L1 and DCP (AHC control group : AUC=0.938; CHB control group : AUC=0.878)  outperformed individual biomarkers ( AHC control group: CHI3L1 AUC=0.888, DCP AUC=0.763; CHB control group: CHI3L1 AUC=0.769, DCP AUC=0.789). Conclusions The integration of CHI3L1 and commonly clinical biomarkers (AFP, AFP⁃L3, DCP) can significantly enhances the auxiliary diagnostic efficacy for HBV⁃related HCC, with particularly demonstrating critical value for early⁃stage HCC, small HCC, and AFP⁃negative cases.

Key words: Chitinase?3?like protein 1, Hepatocellular carcinoma, Small hepatocellular carcinoma, Hepatitis B virus, Alpha fetoprotein