Hepatitis B virus gene integration affects the efficacy of systemic drug therapy after radical resection of liver cancer: A prospective cohort study

Abstract Objective Hepatitis B virus (HBV) gene integration is an important factor in the occurrence and development of HBV-hepatocellular carcinoma (HBV-HCC); however, its role in the clinical treatment of liver cancer is still unclear. This study aimed to investigate the effect of HBV integration on the prognosis of patients. Method Twenty patients with HBV-HCC were included based on strict inclusion criteria. Whole genome sequencing of HBV-HCC surgical specimens was performed to identify HBV gene integration events. After systemic drug treatment (tyrosine kinase inhibitors alone or in combination with immune checkpoint inhibitors), the therapeutic efficacy was evaluated based on RECIST 1.1 criteria. COX regression model was used to identify factors affecting progression-free survival (PFS) and overall survival (OS). Result HCC tissue samples from 20 HBV-HCC patients were sequenced and matched with standard sequence. HBV integration was found in 10 out of the 20 patients. The highest frequency of HBV integration occurred on chromosome 5. Survival analysis showed that HBV integration was a risk factor for HCC recurrence (hazard ratio [HR]: 3.366, P = 0.019). However, there was no significant effect of HBV integration on the PFS after first-line systemic drug treatment ( P = 0.313). The overall survival of HCC patients with HBV integration was significantly shorter than their counterparts without HBV integration (HR [95% CI]: 6.335 [1.237–32.446]; P = 0.027). Conclusion HBV integration event was found to be a risk factor for HCC recurrence in HBV-HCC patients after radical surgery. Patients with HBV integration are potential candidates for active intervention in the early postoperative period.