Background and Aims:Treatment for HCC has evolved rapidly, but the risk of HBV reactivation to new therapies is unclear. We systematically reviewed data on HBV reactivation in patients receiving HCC therapy in relation to use of HBV antiviral prophylaxis.
Approach and Results:A literature search was performed to identify all published studies including HBsAg-positive patients with HCC providing data on HBV reactivation. Forty-one studies with 10,223 patients, all from Asia, were included. The pooled HBV reactivation rate was 5% in patients receiving no specific HCC therapy and was higher in patients undergoing surgical resection (16%), transarterial chemoembolization (19%), or radiotherapy (14%) and intermediate in patients treated with local ablation therapy (7%) or systemic agents (7%). HBV reactivation rates were higher in those without compared to those with HBV prophylaxis (ablation, 9% versus 0%; resection, 20% versus 3%; chemoembolization, 23% versus 1%; external radiotherapy alone, 18% versus 0%; systemic therapy, 9% versus 3%). HBV-related biochemical reactivation rates varied between 6%-11% and 2% in patients receiving HCC therapies with high and intermediate HBV reactivation risk, respectively.Liver decompensation and death were rarely reported (0%-3%) and only in patients receiving HCC treatment with high HBV reactivation risk.
Conclusions: HBsAg-positive patients with HCC are at high or intermediate risk of HBV reactivation depending on the type of HCC therapy. Nucleos(t)ide analogue prophylaxis reduces the risk of HBV reactivation, practically eliminates the risk of hepatitis flare, and should be administered regardless of HCC treatment. This study included patients with HCC treated with no specific HCC therapy or TACE. c This study included patients with HCC treated with no specific HCC therapy, ethanol injection, surgical resection, or TACE. d This study included patients with HCC treated with ablation therapy or TACE. e This study included patients with HCC treated with ablation therapy or surgical resection. f This study included patients with HCC treated with surgical resection or TACE. g This study included patients with HCC treated with radiotherapy with or without TACE. h This study included patients with HCC treated with sorafenib. i This study included patients with HCC treated with sorafenib with or without TACE. j This study included patients with HCC treated with immune checkpoint inhibitors. k This study included patients with HCC treated with immune checkpoint inhibitors with or without antiangiogenetic factors or locoregional therapy. l 72 HBsAg-positive and 6 HBsAg-negative and anti-HBc-positive patients. m 55 HBsAg-positive and 7 HBsAg-negative and anti-HBc-positive patients.