title: Evolution of hepatitis B virus during long-term therapy in patients with chronic hepatitis B.
abstract: BACKGROUND
  Long-term lamivudine (LAM), adefovir (ADV) and entecavir (ETV) treatment induce the emergence of drug-resistant hepatitis B virus (HBV) in patients with chronic hepatitis B infection.
  
  
  OBJECTIVE
  To evaluate the LAM, ADV and ETV resistance mutations detected in our patient group.
  
  
  METHODS
  Twenty patients who had received at least two years of treatment with nucleoside/tide analogues were enrolled in this study. Patients with detectable HBV DNA were analyzed in order to detect resistance mutations and in this group of patients treatment was change.
  
  
  RESULTS
  Three patients developed LAM resistance mutations (2 presented rtM204I and one rtL180M+rtM204V/I) and one patient showed rtN236T ADV resistance mutation. During ADV and LAM treatment, one patient developed ADV plus LAM resistance mutations (rtI163V+rtL180M+rtA181V+rtN236T), in this case, HBV strains harbouring polymerase mutations did not develop LAM associated rtM204V/I primary mutation. In addition, ETV resistance mutations (rtL180M+rtT184A+rtS202G+rtM204V) were detected in one patient.
  
  
  CONCLUSIONS
  These findings suggest that monotherapy resulted in a limited virological response and combination strategies including potent antiviral agents should be recommended for patients with resistant mutations.
authors.affiliation: Department of Immunology, Microbiology and Parasitology, Medicine and Odontology Faculty, University of Basque Country (UPV/EHU), Sarriena Auzoa, 48940 Leioa-Bizkaia, Spain. eli.arrese@ehu.es
authors.forename: Elisabete
authors.initials: E
authors.lastname: Arrese
authors.forename: Miren
authors.initials: M
authors.lastname: Basaras
authors.forename: Sonia
authors.initials: S
authors.lastname: Blanco
authors.forename: Pablo
authors.initials: P
authors.lastname: Ruiz
authors.forename: Ramón
authors.initials: R
authors.lastname: Cisterna
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage*; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine