Abstract
Background & AimsDespite increasing attention to hepatitis B virus (HBV) reactivation in hematologic settings, information on reactivation in hepatitis B surface (HBsAg)-negative patients with hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE).MethodsA total of 109 HBsAg-negative patients with HCC were consecutively recruited for this study and treated with either mono- (n = 75), combination-drug TACE (n = 20), or combination-drug TACE plus radiotherapy (n = 14). With serial monitoring of virological markers every 2–3 months, patients were observed for HBV reactivation (defined as the reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with control subjects with HBsAg-negative cirrhosis (n = 16) or HBsAg loss (n = 46).ResultsDuring the study period, HBV reactivation occurred in 12 (11.0%) and 1 (1.6%) patients in the TACE and control groups, respectively. The median level of HBV DNA at reactivation was 5,174 copies/ml (range: 216–116,058). Of the 12 patients with HBV reactivation, four (33.3%) developed clinical hepatitis, including one patient who suffered from decompensation. All antiviral-treated patients achieved undetectable HBV DNA or HBsAg loss after commencement of antiviral drugs. TACE was significantly correlated with a high incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment. On multivariate analysis, treatment intensity and a prior history of chronic hepatitis B remained independently predictive of reactivation.ConclusionsTACE can reactivate HBV replication in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. Patients with prior chronic HBV infection who are to undergo intensive TACE should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation.
Highlights
Hepatitis B virus (HBV) reactivation is a well-known, potentially life-threatening complication that is often encountered in chronic hepatitis B surface antigen (HBsAg) carriers receiving cancer chemotherapy
Given the observation that the frequency and severity of HBV reactivation are enhanced by the degree of immunosuppression caused by therapy [1,3], host immunity severely downregulated under certain intensive therapies could potentially lead to HBV reactivation even in HBsAg-negative patients with a prior resolved HBV infection
68 patients were excluded from the analysis due to early death within 3 months (6 patients), transfer or loss to follow-up (16 patients), surgery following transarterial chemoembolization (TACE) (9 patients), local ablative therapy (5 patients), supportive care (17 patients), patient refusal (8 patients), co-existing other malignancy (1 patient), or detectable HBV DNA levels (6 patients) at diagnosis of hepatocellular carcinoma (HCC)
Summary
Hepatitis B virus (HBV) reactivation is a well-known, potentially life-threatening complication that is often encountered in chronic hepatitis B surface antigen (HBsAg) carriers receiving cancer chemotherapy. Given the observation that the frequency and severity of HBV reactivation are enhanced by the degree of immunosuppression caused by therapy [1,3], host immunity severely downregulated under certain intensive therapies could potentially lead to HBV reactivation even in HBsAg-negative patients with a prior resolved HBV infection. Such cases of de novo hepatitis B reactivation have often been documented in HBsAg-negative individuals undergoing rituximab-containing chemotherapy or hemato-poietic stem cell transplantation [4,5,6]. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE)
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