title: De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis.
abstract: OBJECTIVE
  To compare efficacy of combined lamivudine (LAM) and adefovir dipivoxil (ADV) therapy with that of entecavir (ETV) monotherapy for hepatitis B virus (HBV)-related decompensated liver cirrhosis.
  
  
  METHODS
  A total of 120 naïve patients with HBV-related decompensated cirrhosis participated in this study. Sixty patients were treated with combined LAM and ADV therapy (LAM + ADV group), while the other 60 were treated with ETV monotherapy (ETV group) for two years. Tests for liver and kidney function, alpha-fetoprotein, HBV serum markers, HBV DNA load, prothrombin time (PT), and ultrasonography or computed tomography scan of the liver were performed every 1 to 3 mo. Repeated measure ANOVA and the χ(2) test were performed to compare the efficacy, side effects, and the cumulative survival rates at 48 and 96 wk.
  
  
  RESULTS
  Forty-five patients in each group were observed for 96 wk. No significant differences in HBV DNA negative rates and alanine aminotransferase (ALT) normalization rates at weeks 48 (χ(2) = 2.12 and 2.88) and 96 (χ(2) = 3.21 and 3.24) between the two groups were observed. Hepatitis B e antigen seroconversion rate in the LAM + ADV group at week 96 was significantly higher in the ETV group (43.5% vs 36.4%, χ(2) = 4.09, P < 0.05). Viral breakthrough occurred in 2 cases (4.4%) by week 48 and in 3 cases (6.7%) by week 96 in the LAM + ADV group, and no viral mutation was detected. In the ETV group, viral breakthrough occurred in 1 case (2.2%) at the end of week 96. An increase in albumin (F = 18.9 and 17.3), decrease in total bilirubin and in ALT (F = 16.5, 17.1 and 23.7, 24.8), reduced PT (F = 22.7 and 24.5), and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores (F = 18.5, 17.8, and 24.2, 23.8) were observed in both groups. The cumulative rates of mortality and liver transplantation were 16.7% (10/60) and 18.3% (11/60) in the LAM + ADV and ETV groups, respectively.
  
  
  CONCLUSIONS
  Both LAM + ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication, improve liver function, and decrease mortality.
authors.affiliation: Jiang-Shan Lian, Lin-Yan Zeng, Jian-Yang Chen, Hong-Yu Jia, Yi-Min Zhang, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Ying-Feng Lu, Ling Zheng, Lan-Juan Li, Yi-Da Yang, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jiang-Shan
authors.initials: JS
authors.lastname: Lian
authors.forename: Lin-Yan
authors.initials: LY
authors.lastname: Zeng
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Chen
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Jia
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Dai-Rong
authors.initials: DR
authors.lastname: Xiang
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Hu
authors.forename: Ying-Feng
authors.initials: YF
authors.lastname: Lu
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Li
authors.forename: Yi-Da
authors.initials: YD
authors.lastname: Yang
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002681:China; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006509:Hepatitis B / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil
keywords: Adefovir dipivoxil; Chronic hepatitis B; Combination therapy; Decompensated liver cirrhosis; Entecavir; Lamivudine