De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

World J Gastroenterol. 2013 Oct 7;19(37):6278-83. doi: 10.3748/wjg.v19.i37.6278.

Abstract

Aim: 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.

Conclusion: Both LAM + ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication, improve liver function, and decrease mortality.

Keywords: Adefovir dipivoxil; Chronic hepatitis B; Combination therapy; Decompensated liver cirrhosis; Entecavir; Lamivudine.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Alanine Transaminase / blood
  • Analysis of Variance
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Chi-Square Distribution
  • China
  • DNA, Viral / blood
  • Drug Therapy, Combination
  • Female
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B / complications
  • Hepatitis B / diagnosis
  • Hepatitis B / drug therapy*
  • Hepatitis B / mortality
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / growth & development
  • Hepatitis B virus / immunology
  • Humans
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use*
  • Prospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Organophosphonates
  • Lamivudine
  • entecavir
  • Guanine
  • Alanine Transaminase
  • Adenine
  • adefovir dipivoxil