Trajectories of Postoperative Hepatitis B Virus (HBV) DNA and HBV-Related Hepatocellular Carcinoma Outcomes: A Longitudinal Multicenter Retrospective Study

Background: Preoperative hepatitis B virus (HBV) DNA level has been shown to correlate with the prognosis of patients with HBV-associated HCC, but its dynamic changes have not been reported. The aim of this study was to describe the trajectory of HBV DNA after R0 liver resection in patients with hepatocellular carcinoma (HCC) receiving antiviral therapy and to investigate its impact on clinical outcomes.Methods: This longitudinal multicenter retrospective study included patients with HBV-related HCC from nine hospitals in China who received antiviral therapy and R0 hepatectomy between 2015 and 2016. A latent class growth mixed model (LCGMM) was applied to group the trajectories of HBV DNA changes. The relative importance of each variable to predict survival was evaluated using the χ2.Findings: Six hundred and eighty-four patients with HCC who met the inclusion exclusion criteria were included. Patients were divided into five trajectories of HBV DNA changes using LCGMM. By combining subgroups with similar survival characteristics, patients were reclassified into three groups: slow decline, slow zeroing, and fast zeroing group, the 5-year OS rates are 34·5%, 53.0%, 70·9%, respectively. Multifactorial COX regression results showed that ALBI grade, HBV reactivation, cirrhosis, maximum tumor diameter, microvascular invasion, and HBV DNA trajectory groups were independent risk factors for OS, and HBV DNA trajectory groups had the highest weight in the relative importance.Interpretation: HBV DNA trajectories were associated with OS for patients with HBV-related HCC after R0 liver resection, and it is necessary to receive antiviral therapy and to monitor HBV status regularly.Funding: This work was supported by the National Key Research and Development Program of China (No: 2022YFC2503700). Declaration of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Ethical Approval: This study was in compliance with the ethical standards of Declaration of Helsinki, and was approved by the Institutional Ethics Committees of the Eastern Hepatobiliary Surgery Hospital, the First Hospital of Wenzhou Medical University, the Second Hospital of Wenzhou Medical University, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, the First Hospital of Jiaxing Affiliated Hospital of Jiaxing University, General Hospital of Northern Theater Command, the Affiliated Hospital of Binzhou Medical College, Sichuan Provincial People's Hospital, and the Sixth People's Hospital of Shenyang. The requirement for informed consent was waived due to the retrospective nature.