High titers of anti-HBs prevent rituximab-related viral reactivation in resolved hepatitis B patient with non-Hodgkin's lymphoma

J Med Virol. 2016 Jun;88(6):1010-7. doi: 10.1002/jmv.24423. Epub 2015 Nov 13.

Abstract

Rituximab, an anti-CD20 monoclonal antibody, is associated with an increased risk of hepatitis B virus (HBV) reactivation. This study aimed to determine the predictive factors for rituximab-related HBV reactivation in resolved hepatitis B patients, defined as HBsAg-negative, anti-HBc-positive, and undetectable HBV DNA. Among 840 consecutive patients with CD20-positive B-cell lymphoma who received rituximab-based chemotherapy from 2003 through 2014 at Seoul National University Hospital, 732 patients were excluded because either anti-HBc was not assessed or they were HBsAg-seropositive. This retrospective study included 108 resolved hepatitis B patients. During a median 33.5-month follow-up period, eight cases of HBV reactivation occurred only among the patients with low anti-HBs titers (<100 mIU/ml) at baseline and those who did not receive antiviral prophylaxis. Using multivariate analyses, antiviral prophylaxis and baseline anti-HBs titers were the protective factors for HBV reactivation (hazard ratio [HR], 0.90 and 0.95, respectively). Among those who did not receive antiviral prophylaxis, patients with high baseline anti-HBs (≥100 mIU/ml) experienced significantly lower risk of HBV reactivation (HR, 0.49; P = 0.006) than the patients with low baseline anti-HBs (<100 mIU/ml) whose cumulative HBV reactivation rates at 6 and 24 months after chemotherapy were 8.3% and 17.3%, respectively. High anti-HBs titer at baseline and antiviral prophylaxis prevented HBV reactivation, suggesting antiviral prophylaxis should be considered according to baseline anti-HBs titer. Meticulous follow-up for ALT and HBV DNA without antiviral prophylaxis might be possible for the patients with high baseline anti-HBs (≥100 mIU/ml).

Keywords: anti-HBs; lymphoma; reactivation; resolved hepatitis B; rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antiviral Agents / therapeutic use
  • DNA, Viral / blood
  • Female
  • Hepatitis B / complications
  • Hepatitis B / immunology*
  • Hepatitis B / virology
  • Hepatitis B Antibodies / blood*
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B virus / physiology*
  • Humans
  • Lymphoma, Non-Hodgkin / complications
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / immunology*
  • Lymphoma, Non-Hodgkin / virology
  • Male
  • Middle Aged
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Rituximab / adverse effects*
  • Rituximab / therapeutic use
  • Serologic Tests
  • Virus Activation / drug effects*
  • Virus Activation / immunology*

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Rituximab