Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy

Abstract

Background: Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients.

Methods: Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes.

Results: There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors.

Conclusions: Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients receiving chemotherapy. Cancer 2017;123:3367-76. © 2017 American Cancer Society.

Keywords: antiviral therapy; cancer; hematologic malignancies; hepatitis B; hepatitis B reactivation; hepatitis B screening; hepatitis flare; liver failure.

Figure 1. Timeline of study periods

Abbreviation: Chemo: chemotherapy. Chemotherapy initiation: 2 months before first chemotherapy administration until administration of second cycle of chemotherapy. Post-chemotherapy initiation: after administration of second cycle of chemotherapy until end of study period, 2011. HBV identification. Early: Positive findings on HBsAg or anti-HBc tests performed before or during chemotherapy initiation period or anti-HBV therapy prior to first chemotherapy. Late: Positive findings on HBsAg or anti-HBc tests performed after chemotherapy initiation period. Anti-HBV therapy initiation. Early: HBV medication started during chemotherapy initiation period and before any adverse liver outcome. Late: HBV medication started after chemotherapy initiation, before or after any adverse liver outcome. Outcomes: from administration of second cycle of chemotherapy up to two years after last chemotherapy administration at MD Anderson, last follow up, or death.

Figure 2

Cumulative incidence of liver failure in chronic HBV patients with solid tumors, by timing of HBV identification