title: Hepatitis B virus reactivation after fludarabine-based regimens for indolent non-Hodgkin's lymphomas: high prevalence of acquired viral genomic mutations.
abstract: OBJECTIVE
  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.
  
  
  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 x 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.
  
  
  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.
authors: Divisione di Ematologia, II University, Naples, Italy.
authors: Marco
authors: M
authors: Picardi
authors: Fabrizio
authors: F
authors: Pane
authors: Concetta
authors: C
authors: Quintarelli
authors: Amalia
authors: A
authors: De Renzo
authors: Annalisa
authors: A
authors: Del Giudice
authors: Bianca
authors: B
authors: De Divitiis
authors: Marcello
authors: M
authors: Persico
authors: Rosanna
authors: R
authors: Ciancia
authors: Francesco
authors: F
authors: Salvatore
authors: Bruno
authors: B
authors: Rotoli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D002353:Carrier State; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006509:Hepatitis B / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D006510:Hepatitis B Antibodies / Q000097:blood; D006511:Hepatitis B Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D017093:Liver Failure / Q000209:etiology; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017385:Sequence Homology; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens; D018937:Hepatitis C Antibodies; D019259:Lamivudine; D014740:Vidarabine; C024352:fludarabine