Abstract: Objective The aim of this study was to investigate the efficacy of programmed death 1(PD-1) immunocheckpoint inhibitors (ICIs) and tyrosine kinase inhibitor (TKIs) combination in patients with hepatitis B virus (HBV)-associated advanced hepatocellular carcinoma (aHCC). Methods 44 patients with HBV-related unresectable HCC (normal serum AFP level in 16 cases and elevated in 28 cases) were enrolled in Fifth Medical Center, General Hospital of People's Liberation Army between September 2019 and January 2022, and all received sintilimab, camrelizumab, tirelizhu and lenvatinib combination therapy for 2 to 24 months, with median of 8(6, 26) months. All patients were followed-up for 24(10,36) months. Results Both two patients in groups of normal serum AFP and elevated levels lost in our series; the objective remission rate and disease control rate in patients with normal serum AFP level were 21.4% and 28.6%, both not significantly different as compared to 11.5% and 23.1% in patients with elevated serum AFP level (P>0.05); out of the 14 patients with normal serum AFP level, 4 died, with the median overall survival (mOS)of 17.1(14.0, 24.0)mon, while in those with elevated serum AFP level, 18 died, with the mOS of 8.6(4.8, 18.1)mon(P=0.01). Conclusion The patients with unresectable HBV-related HCC might get benefits from the combination of ICIs and TKIs therapy, and the emphasis should put on those with elevated serum AFP levels.

Key words: Hepatoma, Immunocheckpoint inhibitors, Tyrosine kinase inhibitor, Alpha-fetoprotein, Therapy