Add-On Adefovir Is Superior to a Switch to Entecavir as Rescue Therapy for Lamivudine-Resistant Chronic Hepatitis B

Department of Internal Medicine, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea.
Digestive Diseases and Sciences (Impact Factor: 2.55). 07/2011; 56(7):2130-6. DOI: 10.1007/s10620-010-1561-2
Source: PubMed

ABSTRACT Lamivudine (LAM) has been extensively used to treat hepatitis B, but high incidence of drug resistance has required rescue studies. We validated the optimum treatment strategy for LAM-resistant patients by means of a comparative study of add-on adefovir (ADV) and a switch to entecavir (ETV).
We assessed the virologic response in consecutive LAM-resistant patients who received add-on ADV or a switch to ETV.
The mean reduction of serum hepatitis B virus (HBV) DNA levels was significantly less in the ETV group than in the add-on ADV group (-3.45 vs. -4.17; P = 0.047 at week 24 and -3.81 vs. -4.68 log(10) IU/mL; P = 0.044 at week 48). Achievement of undetectable HBV DNA was significantly lower in the ETV group than in the add-on ADV group (P = 0.043). Multivariate analysis showed that add-on ADV, baseline HBV DNA levels, and initial virologic response were significant predictors of HBV DNA negativity (adjusted OR, 2.582; P = 0.008, 0.304; P = 0.001, and 5.928; P = 0.001). Virologic breakthrough was observed for 12 patients, in the ETV group only.
Add-on ADV was more effective and durable than ETV as rescue therapy. Therefore, add-on ADV might be the preferred strategy for LAM-resistant patients who need long-term antiviral treatment.


Available from: Won Kim, Apr 19, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background/Aims Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option for patients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies. Methods Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower limitation of detection, < 140 copies/mL), biochemical response (alanine aminotransferase < 40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough. Results Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P=0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001). Conclusions Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.
    09/2014; 20(3):267-73. DOI:10.3350/cmh.2014.20.3.267
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background/Aims Quantitation of hepatitis B surface antigen (HBsAg) is an increasingly popular method to determine the treatment response in chronic hepatitis B (CHB) patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine (LMV)-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV-resistant CHB patients treated with adefovir (ADV) add-on therapy. Methods LMV-resistant CHB patients treated with LMV-ADV combination therapy for over 2 years were included. HBsAg levels were measured at 6 month intervals until 1 year, and annually thereafter. Treatment response was assessed by determining the virological response (VR, undetectable HBV DNA levels) during treatment. Results Fifty patients were included, of which 40 showed a VR. HBsAg levels were not different significantly at baseline (4.0 vs. 3.6 Log10 IU/mL, P=0.072). However, the HBsAg level decreased after 6 months of treatment in patients with a VR and became different significantly between the groups thereafter (3.9 vs. 3.3 at 6 months, P=0.002; 3.8 vs. 3.2 at 1 year, P=0.004; 3.9 vs. 3.2 at 2 years, P=0.008; 3.7 vs. 3.1 at 3 years, P =0.020). Conclusions The HBsAg level at 6 months after treatment can help predict treatment response.
    09/2014; 20(3):274-82. DOI:10.3350/cmh.2014.20.3.274
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: This study investigated the antiviral efficacy of adefovir (ADV) rescue therapy and the feasibility of lamivudine (LAM) discontinuation in LAM-resistant chronic hepatitis B (CH-B) patients who had attained a virological response (VR) with LAM + ADV combination therapy. Methods: The VR and virological breakthrough (VBT) were analyzed in 106 consecutively enrolled LAM-resistant CH-B patients who received ADV rescue therapy during a mean follow-up period of 55.2 months. Seventy-four patients achieved VR, and were divided into the LAM-discontinuation group (n = 39) and the LAM-continuation group (n = 35). The VR and VBT between the 2 groups were compared. Results: For all 106 LAM-resistant CH-B patients, the overall cumulative probabilities of VR at 1, 2, 3 and 5 years of ADV rescue therapy were 40.6, 55.7, 64.6 and 81.3%, respectively. The cumulative probabilities of VBT at 1, 2, 3 and 5 years were 0, 2.9, 8.8 and 13.9%, respectively. Whether they discontinued or continued LAM after achieving VR on LAM + ADV therapy, VR and VBT were not significantly different during a mean follow-up period of 40.4 months. Conclusions: There was a good long-term VR with ADV rescue therapy for LAM-resistant CH-B patients. Moreover, discontinuing LAM was found to be feasible for patients who attained VR during ADV + LAM therapy. © 2014 S. Karger AG, Basel.
    Intervirology 09/2014; 57(6):337-343. DOI:10.1159/000365757 · 1.77 Impact Factor