Postoperative hepatitis B virus reactivation and its impact on survival in HBV-related hepatocellular carcinoma patients undergoing conversion therapy with interventional therapy combined with tyrosine kinase inhibitors and immune checkpoint inhibitors

• Published in: Frontiers in cellular and infection microbiology Vol. 15; p. 1598193
• Main Authors: Xu, Shaowei, Pang, Qingqing, Wei, Meng, Liu, Danxi, Yuan, Du, Bai, Tao, Wang, Xiaobo, Tang, Zhihong, Wu, Feixiang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2025
• Subjects: Adult; Aged; Antiviral Agents - therapeutic use; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - surgery; Carcinoma, Hepatocellular - therapy; Carcinoma, Hepatocellular - virology; Cellular and Infection Microbiology; Chemoembolization, Therapeutic; conversion therapy; DNA, Viral; Female; HBV reactivation; Hepatitis B - complications; Hepatitis B - drug therapy; Hepatitis B - virology; Hepatitis B virus - drug effects; Hepatitis B virus - physiology; hepatocellular carcinoma; Humans; Immune Checkpoint Inhibitors - therapeutic use; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Liver Neoplasms - surgery; Liver Neoplasms - therapy; Liver Neoplasms - virology; Male; Middle Aged; Protein Kinase Inhibitors - therapeutic use; Retrospective Studies; Risk Factors; surgery; survival; Tyrosine Kinase Inhibitors; Virus Activation - drug effects; conversion therapy; HBV reactivation; hepatocellular carcinoma; survival; surgery
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2025.1598193

This study aimed to investigate hepatitis B virus (HBV) reactivation and its impact on postoperative survival in patients with HBV-related hepatocellular carcinoma (HCC) who underwent conversion therapy. The therapeutic regimen consisted of interventional procedures (hepatic artery infusion chemotherapy [HAIC] and/or transarterial chemoembolization [TACE]) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). A retrospective analysis was performed at a single institution involving 91 patients initially unresectable HCC linked to the hepatitis B virus. These patients achieved resectability following conversion therapy and subsequently underwent surgical tumor removal. Logistic regression identified risk factors for HBV reactivation (HBVr). Kaplan-Meier survival analysis and log-rank tests assessed survival differences. Cox proportional hazards regression was used to identify independent predictors of progression-free survival (PFS) and overall survival (OS). In our cohort, HBVr occurred in 17 patients (18.7%), all of whom received antiviral therapy. The incidence of HBVr was 16.7% (14/84) in patients with detectable baseline HBV DNA and 42.9% (3/7) in those with undetectable levels. Baseline HBV DNA ≥2000 IU/ml was identified as an independent protective factor against HBVr (OR 0.090, 95% CI 0.015-0.532; P = 0.008). The median PFS was significantly shorter in the reactivation group than in the non-reactivation group (12.1 months [95% CI 5.5-18.7] . 29.2 months [95% CI 23.6-34.7]; P < 0.001). However, no significant difference was observed in median OS between the two groups (not reached . 45.6 months [95% CI 41.7-49.5]; P = 0.117). HBVr represents a potential complication in subjects receiving hepatectomy for hepatitis B virus associated HCC following conversion therapy involving interventional therapies combined with TKIs and ICIs. Patients experiencing HBVr exhibited significantly shorter progression-free survival compared to those without reactivation. Therefore, prophylactic antiviral therapy and meticulous HBV DNA monitoring are warranted during both conversion therapy and the perioperative period.