Abstract:Objective To evaluate the diagnostic value of abnormal prothrombin (des-gamma-carboxy prothrombin, DCP), Golgi protein 73 (GP73) and α-hydroxybutyrate dehydrogenase (α-HBDH) in the patients with alpha-fetoprotein（AFP）-negative primary hepatocellular carcinoma (PHCC). Methods A retrospective analysis was conducted on the patients with hepatitis B virus (HBV) infection treated in Second Hospital of Nanjing from January 2021 to December 2022, including 88 PHCC patients with negative AFP (PHCC group), 84 patients with hepatitis cirrhosis (cirrhosis group) and 75 patients with chronic hepatitis B (hepatitis group). At the same time, 67 healthy persons were served as control group. The serum DCP, GP73 and α-HBDH levels were detected and compared among these groups to assess the diagnostic efficacy of the three indicators (alone or in combination) for AFP-negative PHCC by drawing receiver operating characteristic (ROC) curve. Results The levels of DCP, GP73 and α-HBDH in PHCC group were significantly higher than those in cirrhosis group, hepatitis group and control group (P＜0.05), respectively. In the diagnosis of AFP-negative PHCC, the area under ROC (AUC) of combined detection of DCP, GP73 and α-HBDHwas 0.889, which was higher than that of DCP (0.804), GP73 (0.748) and α-HBDH (0.800) individually, and there were significant differences (Z =3.087, 3.350, 3.042, P＜0.01). The sensitivity (92.04%), specificity (96.03%) and accuracy (91.09%) of combined detection were the highest, followed by those of alone DCP (56.82%, 91.82%, 79.35%, respectively). Conclusion DCP, GP73 and α-HBDH have certain value in diagnosing AFP-negative PHCC, and the combined detection is helpful to improve the diagnostic efficiency.