title: Efficacy of entecavir and adefovir combination therapy for patients with lamivudine- and entecavir-resistant chronic hepatitis B.
abstract: BACKGROUND
  The optimal treatment of patients with chronic hepatitis B (CHB) who develop resistance to both lamivudine (LMV) and entecavir (ETV) after sequential monotherapy of LMV and ETV remains little known.
  
  
  METHODS
  We evaluated the efficacy of entecavir (ETV) plus adefovir dipivoxil (ADV) combination therapy for patients with resistance to LMV and ETV. We reviewed the medical records of 12 patients, and treated all 12 patients with ETV plus ADV combination therapy for at least 18 months. Quantitative hepatitis B virus (HBV) DNA levels, serologic markers, and hepatic panel values were monitored at baseline and 3-month intervals thereafter for 18 months.
  
  
  RESULTS
  The baseline mean serum HBV DNA level was 7.26 ± 1.11 log(10) copies/ml. The mean reductions in serum HBV DNA levels from baseline to 3, 6, 9, 12, 15, and 18 months were -1.98 ± 1.03, -2.87 ± 1.02, -3.32 ± 1.10, -3.92 ± 1.30, -4.36 ± 1.22, and -4.57 ± 1.18 log(10) copies/ml, respectively. Complete virological response (HBV DNA of <2 log(10) copies/ml) at 6, 12, and 18 months was observed in 1 (8.3%), 4 (33.3%), and 6 (50.0%) patients, respectively. The 2 patients with baseline HBV DNA of <6 log(10) copies/ml achieved complete virological response at 18 months, while 4 of 10 patients with baseline HBV DNA of ≥6 log(10) copies/ml achieved complete virological response at 18 months. None of the 12 patients experienced virological breakthrough during follow-up.
  
  
  CONCLUSIONS
  ETV plus ADV combination therapy effectively reduced serum HBV DNA levels in patients with CHB who developed resistance to both LMV and ETV. Additional long-term studies are needed to assess the effect of long-term treatment with these drugs.
authors.affiliation: Department of Internal Medicine, College of Medicine, Kyung Hee University, 149 Sangil-dong, Gangdong-gu, Seoul 134-727, Korea.
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Jeon
authors.forename: Hyun Phil
authors.initials: HP
authors.lastname: Shin
authors.forename: Joung Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Kwang Ro
authors.initials: KR
authors.lastname: Joo
authors.forename: Jae Myung
authors.initials: JM
authors.lastname: Cha
authors.forename: Jae Jun
authors.initials: JJ
authors.lastname: Park
authors.forename: Jun Uk
authors.initials: JU
authors.lastname: Lim
authors.forename: Kyuseong
authors.initials: K
authors.lastname: Lim
authors.forename: Sunyong
authors.initials: S
authors.lastname: Kim
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D004279:DNA, Viral / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine