title: [Efficacy of 48-week tenofovir disoproxil fumarate therapy in patients who were unresponsive to nucleoside-analogue treatments].
abstract: OBJECTIVE
  To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).
  
  
  METHODS
  A total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method.
  
  
  RESULTS
  Over the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period.
  
  
  CONCLUSIONS
  For CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.
authors.affiliation: Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Huang
authors.forename: Xinhua
authors.initials: X
authors.lastname: Li
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Wu
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Jie
authors.forename: Xiangyong
authors.initials: X
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Guoli
authors.initials: G
authors.lastname: Lin
authors.forename: Fangji
authors.initials: F
authors.lastname: Yang
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Ao
authors.forename: Yihua
authors.initials: Y
authors.lastname: Pang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Yutian
authors.initials: Y
authors.lastname: Chong
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine