Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition

Abstract

BackgroundHepatitis B virus (HBV) reactivation is a serious complication in patients with cancers and HBV infection undergoing immunosuppressant treatment or chemotherapy. However, the safety of anti-programmed cell death (PD) -1 and anti-programmed cell death-ligand 1 (PD-L1) therapy in these patients is unknown because they were excluded from clinical trials of immunotherapy.MethodsThis retrospective cohort study involved consecutive hepatitis B surface antigen (HBsAg) -positive cancer patients who were referred to Sun Yat-sen University Cancer Center and received an anti-PD-1/PD-L1 antibody between January 1, 2015 and July 31, 2018. The primary end point was the rate of the occurrence of HBV reactivation.ResultsIn total, 114 eligible patients were included, among whom 90 (79%) were male, and the median (range) age was 46 (16–76) years. Six patients (5.3%) developed HBV reactivation, occurring at a median of 18 weeks (range, 3–35 weeks) from the commencement of immunotherapy. Among these patients, all of them had undetectable baseline HBV DNA; one had prophylactic antiviral therapy while five did not; four were positive for Hepatitis B e antigen while the other two were negative. At reactivation, the median HBV DNA level was 3.89 × 104 IU/mL (range, 1.80 × 103–6.00 × 107 IU/mL); five had HBV-related hepatitis and one exhibited increasing HBV DNA level without alanine transaminase elevation. No HBV-related fatal events occurred. The lack of antiviral prophylaxis was the only significant risk factor for HBV reactivation (odds ratio, 17.50 [95% CI, 1.95–157.07], P = .004).ConclusionsHBV reactivation occurs in a subset of HBsAg-positive cancer patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy. Regular monitoring of HBV DNA and antiviral prophylaxis are advised to prevent this potentially fatal complication.

Risk of HBV reactivation in patients with immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma

“… 11 In addition to the previous case reports, 17 18 40 a recent Chinese study demonstrated that 6 of 114 (5.3%) HBsAg-positive patients with various cancers developed HBV reactivation during anti-PD-1/PD-L1 treatment, but no HBV-related fatal events occurred. 41 Our real-world data also demonstrated that HBV reactivation would occur in one out of six patients who did not receive pre-emptive anti-viral treatment. Accordingly, we still have to keep awareness of HBV reactivation during ICI treatment for HBV-HCC.…”

Hepatitis B virus persistence and reactivation

“…Immune checkpoint inhibitors are increasingly used in the treatment of a broad spectrum of solid cancers by restoring anti-tumor T cell functions. A retrospective study reported that six of 114 (5.3%) cancer patients with chronic HBV infection experienced HBV reactivation at a median of 18 weeks from the onset of anti-PD-1 or PD-L1 immunotherapy 176. This was unexpected because the immunotherapy overcomes T cell exhaustion and then impairs control of viral replication.…”

Reactivation of Hepatitis B Virus Among Patients With Cancer Receiving Immunotherapy

“…However, when the analysis was limited to the subset of patients with undetectable HBV DNA at baseline who were not receiving antiviral prophylaxis prior to ICI initiation, the incidence of HBV reactivation was higher, 20.8% (5/24). 6 HBV reactivation resolved in all five patients after initiation of antiviral therapy; subsequent ICI treatment was delayed for three of these patients.…”