HBV integration affect the efficacy of systematic drug therapy after radical resection of liver cancer: a prospective cohort study

Abstract Objective: HBV gene integration event is an important factor to reveal the occurrence and development of HBV-HCC, but its role in the clinical treatment of liver cancer is still unclear. This study intends to collect HCC patients, find HBV integration events based on whole genome sequencing (WGS), and finally determine their impact on the clinical prognosis of patients. Method: After strict screening of inclusion and exclusion criteria, 20 HBV-HCC patients were finally included, and the whole genome of cancer tissue was sequenced to identify HBV gene integration events. After systematic drug treatment (TKIs or combined with ICIs), the efficacy was evaluated based on RECIST 1.1 criteria. COX regression model was used to analyze the factors affecting PFS and OS of HCC patients, and Kaplan-meier method was used to draw the survival curve. Result: In this study, a total of 20 HBV-HCC patients were included, and HCC tissue samples were sequenced and matched with standard sequence. Among them, HBV integration events were found in 10 HBV-HCC patients, and the highest number of integration events in a single sample was 7. The highest frequency of HBV integration occurred on chromosome 5. The baselines of non-integration group and integration group are consistent and comparable. Survival analysis showed that HBV integration was a risk factor for HCC recurrence, with HR value of 3.366, P=0.019. However, in the PFS outcome of first-line systematic drug treatment, there was no significant difference between the two groups, P=0.313. Compared with the control group, the survival period of HCC patients with HBV integration was shorter, HR (95% CI): 6.335 (1.237-32.446) (P=0.027). In terms of the choice of different treatment methods, due to the limited sample size, the differences observed were not statistically significant. Conclusion: HBV integration event is not only a risk factor for the occurrence and development of HCC, but also a risk factor for the recurrence of HBV-HCC patients after surgery. The highest frequency of HBV integration occurred on chromosome 5. HBV integration events significantly shortened the survival period of patients, and should be actively intervened in the early postoperative period.