title: Antiviral effect of entecavir in chronic hepatitis B: influence of prior exposure to nucleos(t)ide analogues.
abstract: OBJECTIVE
  Entecavir is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B patients, but data on the efficacy in NA-experienced subjects are limited.
  
  
  METHODS
  In a multi-center cohort study we investigated 161 chronic hepatitis B patients (34% NA-experienced) treated with entecavir monotherapy.
  
  
  RESULTS
  During a median follow-up of 11 (3-23)months, 82 (79%) of 104 NA-naïve patients achieved virologic response (VR), defined as HBV DNA <80IU/ml, and none of the patients (0%) developed genotypic entecavir-resistance. VR was demonstrated in 31 (54%) of 57 NA-experienced patients during a median follow-up of 12 (3-31)months. Patients with lamivudine-resistant mutations at the start of entecavir monotherapy had a reduced probability of achieving VR compared to lamivudine-naïve patients (HR 0.14; 95% CI 0.04-0.58; p=0.007). Antiviral efficacy was not decreased by prior treatment with lamivudine when lamivudine-resistance had never developed (HR 0.81; 95% CI 0.43-1.52; p=0.52). Prior adefovir therapy without development of adefovir-resistance (HR 0.84; 95% CI 0.43-1.64; p=0.61) and presence of adefovir-resistance (HR 0.86; 95% CI 0.27-2.71; p=0.80) did not influence antiviral response to entecavir. Switching to a tenofovir-containing treatment regimen resulted in viral load decline in patients with entecavir-resistance associated mutations.
  
  
  CONCLUSIONS
  Entecavir proved to be efficacious in NA-naïve patients. The antiviral efficacy of entecavir was not influenced by prior treatment with adefovir or presence of adefovir-resistance. Entecavir should not be used in patients with previous lamivudine-resistance, yet it may still be an option in lamivudine-experienced patients in case lamivudine-resistance never developed.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Gravendijkwal 230, Room Ha 204, Rotterdam, The Netherlands.
authors.forename: Jurriën G P
authors.initials: JG
authors.lastname: Reijnders
authors.forename: Katja
authors.initials: K
authors.lastname: Deterding
authors.forename: Jörg
authors.initials: J
authors.lastname: Petersen
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Florian
authors.initials: F
authors.lastname: van Bömmel
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine