title: High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B.
abstract: OBJECTIVE
  Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance.
  
  
  METHODS
  Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log(10) copies/mL after 6 months of combination therapy.
  
  
  RESULTS
  The IVR rate was 76%. The proportion of patients with a high viral load (≥5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%).
  
  
  CONCLUSIONS
  ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.
authors.affiliation: Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea. hbchae@chungbuk.ac.kr
authors.forename: Hee Bok
authors.initials: HB
authors.lastname: Chae
authors.forename: Mee Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Eui Geun
authors.initials: EG
authors.lastname: Seo
authors.forename: Yong Hyeok
authors.initials: YH
authors.lastname: Choi
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Joung Ho
authors.initials: JH
authors.lastname: Han
authors.forename: Soon Man
authors.initials: SM
authors.lastname: Yoon
authors.forename: Seon Mee
authors.initials: SM
authors.lastname: Park
authors.forename: Sei Jin
authors.initials: SJ
authors.lastname: Youn
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024921:Drug Resistance, Multiple, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D063065:Organophosphonates; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000410:Alanine Transaminase; D000225:Adenine