title: Simultaneous emergence of entecavir resistance mutations in a nucleoside-naive chronic hepatitis B patient.
abstract: BACKGROUND
  Entecavir (ETV) has potent antiviral activity against hepatitis B virus (HBV), and the emergence of drug resistance is rare in nucleoside-naive patients. Resistance requires simultaneous appearance of three mutations which account for the very low resistance profile of ETV. We experienced one case of genotypic ETV resistance with viral rebound during ETV treatment of nucleoside-naive patients with chronic hepatitis B (CHB).
  
  
  METHODS
  A 50-year-old HBV e antigen-positive man received ETV 0.5 mg/day for 120 weeks. The level of HBV DNA was 9.0 log(10) copies/ml at baseline, declined to a nadir of 2.7 at week 60 and then rebounded to 6.0 at week 108 and 7.5 at week 120. The serum alanine aminotransferase level did not increase during ETV treatment. The ETV resistance-related substitution (T184A) and lamivudine resistance-related substitutions (L180M and M204V) were detected by sequence analysis at week 96.
  
  
  CONCLUSIONS
  The three substitutions associated with ETV and lamivudine resistance developed simultaneously without complete suppression in a nucleoside-naive CHB patient after extended therapy. In spite of the extremely rare chance of viral mutation during ETV treatment, treatment-naive patients with high pretreatment viral loads and detectable HBV DNA during treatment should be carefully monitored or undergo targeted surveillance for resistance.
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun Woong
authors.initials: HW
authors.lastname: Lee
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sun Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Bong Ki
authors.initials: BK
authors.lastname: Cha
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Chang
authors.forename: Chang Hwan
authors.initials: CH
authors.lastname: Choi
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Do
authors.forename: Jae Gyu
authors.initials: JG
authors.lastname: Kim
authors.forename: Sae Kyung
authors.initials: SK
authors.lastname: Chang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense
chemical_list: D000998:Antiviral Agents; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase