Hepatitis B virus reactivation after fludarabine-based regimens for indolent non-Hodgkin's lymphomas: High prevalence of acquired viral genomic mutations

Marco Picardi, Fabrizio Pane, Concetta Quintarelli, Amalia De Renzo, Annalisa Del Giudice, Bianca De Divitiis, Marcello Persico, Rosanna Ciancia, Francesco Salvatore, Bruno Rotoli

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives. Chemotherapy can cause hepatitis flare-up through viral reactivation in patients who have had contact with hepatitis viruses. Few data are available on the genotype of the reactivated viruses. Design and Methods. In 40 consecutive adult patients with indolent non-Hodgkin's lymphoma (NHL) receiving fludarabine-based front-line chemotherapy, we performed a prospective study on viral hepatitis reactivation and analyzed the genotype of the reactivated viruses. Before chemotherapy, 4 patients were healthy carriers of hepatitis B surface antigen (HBsAg), 2 had HB core antigen antibodies (anti-HBc), 6 anti-HBs and 6 anti-HCV; 22 were seronegative. Results. Hepatitis flare-up occurred in the 4 HBsAg-positive patients and in 1 anti-HBc-positive patient at a median of 1 month (range 1-4) after chemotherapy, when the CD4/CD8 ratio was still inverted. HBV reactivation was documented in all 5 instances (HBV-DNA 2-8×10 6 copies/mL). Two of the 5 patients responded to lamivudine, whereas 1 died of acute liver failure and 2 had persistent severe hepatitis. HBV genome sequencing at hepatitis flare-up showed that deviation from the closest related published sequences was 1.0% and 1.1% in the 2 lamivudine-responsive patients, and 1.5%, 1.8% and 1.7% in the 3 lamivudine-resistant patients. The polymerase open reading frame (ORF) and the HBs ORF of lamivudine-resistant strains contained several novel amino acid substitutions. Interpretation and Conclusions. These results suggest that fludarabine treatment of HBV-infected patients is frequently associated with acute hepatitis due to viral reactivation, and that lamivudine may be less effective in this situation than in other settings of immunocompromised hosts because of the emergence of resistant mutant strains.

Original languageEnglish
Pages (from-to)1296-1303
Number of pages8
JournalHaematologica
Volume88
Issue number11
Publication statusPublished - Nov 2003

Keywords

  • Fludarabine
  • HBV
  • NHL
  • Viral genomic mutations

ASJC Scopus subject areas

  • Hematology

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