HBV reactivation and its effect on survival in HBV-related hepatocarcinoma patients undergoing transarterial chemoembolization combined with tyrosine kinase inhibitors plus immune checkpoint inhibitors

Abstract

ObjectiveThis study aimed to access hepatitis B virus (HBV) reactivation and its effect on survival in HBV-related hepatocarcinoma (HCC) patients who underwent transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs).MethodsIn this single-center retrospective study, we enrolled 119 HBV-related unresectable advanced HCC patients receiving TACE combined with TKIs plus ICIs. Risk factors for HBV reactivation were analyzed by logistic regression. Kaplan-Meier method was applied to draw the survival curve, and log-rank test was used to compare survival between patients with and without HBV reactivation.ResultsA total of 12 patients (10.1%) encountered HBV reactivation in our study, of which only 4 patients received antiviral prophylaxis. The incidence of HBV reactivation was 1.8% (1/57) in patients with detectable baseline HBV DNA and 4.2% (4/95) in patients with antiviral prophylaxis respectively. Lack of prophylactic antiviral treatment (OR=0.047, 95%CI 0.008-0.273, P=0.001) and undetectable HBV DNA (OR=0.073, 95%CI 0.007-0.727, P=0.026) were independent risk factors for HBV reactivation. The median survival time (MST) for all patients was 22.4 months. No survival difference was observed in patients with or without HBV reactivation. (MST: undefined vs 22.4 months, log-rank test: P=0.614).ConclusionHBV reactivation could occur in HBV-related HCC patients who treated with TACE in combination with TKIs plus ICIs. Before and during the combination treatment, it is necessary to routinely monitor HBV DNA and to take effective prophylactic antiviral therapy.

Risk of hepatitis B virus reactivation and its effect on survival in advanced hepatocellular carcinoma patients treated with hepatic arterial infusion chemotherapy and lenvatinib plus programmed death receptor-1 inhibitors

“…However, HBV reactivation occurred in some patients despite prophylactic antiviral therapy. This is a common phenomenon and has been reported in many studies ( Shen et al., 2023 ; Jang, 2014 ; Hsu et al., 2014 ). This could be attributed to the development of resistance to antiviral therapy due to previous exposure to therapy ( Tenney et al., 2009 ; Guo et al., 2018 ).…”

“…This could be because HAIC, a locoregional therapy, can increase the risk of viral reactivation. According to some studies, TACE, another locoregional therapy, is a risk factor for HBV reactivation, and the incidence of reactivation in patients treated with TACE was 10–35% ( Shen et al., 2023 ; Jang, 2014 ). Another reason could be that combination treatment increases the risk of HBV reactivation.…”

“…Over the past few years, HBV reactivation has been observed after anti-tumor treatment, including interventional therapy, TKIs, and PD1s ( Loomba and Liang, 2017 ; Shen et al., 2023 ). A retrospective study reported that HCC patients treated with TKIs plus PD1s could suffer HBV reactivation and combination therapy was a risk factor for reactivation of HBV ( Lei et al., 2023 ).…”

“…TACE, another locoregional therapy, is a risk factor for HBV reactivation, and the incidence of reactivation in patients treated with TACE was 10-35% (Shen et al, 2023;Jang, 2014). Another reason could be that combination treatment increases the risk of HBV reactivation.…”

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

“…These therapies can enhance immune surveillance and facilitate viral clearance. Interferons are a class of cytokines that elicit anti-viral responses, augmenting the immune system’s capacity to identify and counteract viral infections[ 140 , 144 ]. In the setting of HBV reactivation, therapies based on interferon can elicit immune responses that are both innate and adaptive.…”