Adding adefovir vs. switching to entecavir for lamivudine‐resistant chronic hepatitis B (<scp>ACE</scp> study): a 2‐year follow‐up randomized controlled trial

Yim, Hyung Joon; Seo, Yeon Seok; Yoon, Eileen L.; Kim, Chang Wook; Lee, Chang Don; Park, Sang Hoon; Lee, Myung Seok; Park, Choong Kee; Chae, Hee Bok; Kim, Moon Young; Baik, Soon Koo; Kim, Yun Soo; Kim, Ju Hyun; Lee, Jung Il; Lee, Jin Woo; Hong, Sun; Um, Soon Ho

doi:10.1111/liv.12036

Cited by 23 publications

(19 citation statements)

References 32 publications

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“…However, according to our data, the LAM+ADV combination therapy, which is considered a preferred therapy for LAM-resistant CHB patients because it induces less drug resistance and high viral response, did not show a higher viral suppressive effect than the monotherapies considering the mean HBV DNA levels. In terms of virologic response rates, LAM+ADV combination therapy for 1 year showed undetectable HBV DNA rates of 40% to 70% in previous studies for LAM-resistant CHB patients 13,14. However, in our study, this group showed low virologic response (21.2% of patients with undetectable HBV DNA), whilst 57.1% patients in the CLV+ADV combination therapy group showed undetectable HBV DNA.…”

Section: Discussioncontrasting

confidence: 77%

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Management of Clevudine-Resistant Chronic Hepatitis B: A Multicenter Cohort Study

et al. 2017

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Background/AimsData are lacking regarding the management of chronic hepatitis B (CHB) with resistance to clevudine (CLV). This study evaluated the efficacy of different rescue therapies for CLV-resistant CHB.MethodsPatients with CLV-resistant CHB were enrolled in the cohort, and all patients developed virologic breakthrough during CLV therapy and had confirmed-genotypic resistance to CLV (rtM204I mutation) before enrollment.ResultsOf the 107 patients, 12 received adefovir (ADV), 21 received a CLV plus ADV combination (CLV+ADV), 34 received a lamivudine plus ADV combination (LAM+ADV), and 40 received entecavir (ETV) therapy for 48 weeks. The CLV+ADV group had the lowest hepatitis B virus (HBV) DNA level (p<0.0001) and showed the greatest reduction of HBV DNA levels from baseline compared to all other groups (p=0.004) at week 48. HBV DNA was undetectable (<70 IU/mL) in 0%, 57.1%, 21.2%, and 27.5% (p=0.003) of the patients in each group, respectively, at week 48. At the end of the study, the mean alanine transaminase (ALT) level, rate of ALT normalization, and rate of hepatitis B envelope antigen loss or seroconversion did not differ between groups.ConclusionsCLV+ADV combination therapy in patients with CLV-resistant CHB more effectively suppresses HBV replication than ETV, ADV, or LAM+ADV therapy.

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Section: Discussioncontrasting

confidence: 77%

“…This prevents us from recommending CLV+ADV combination for CLV-resistant CHB routinely. In addition, ADV has potential risk of nephrotoxicity, and one patient of our cohort displayed increase of serum creatinine 14,24. Hence CLV+ADV combination therapy can only be recommend with caution of these adverse events.…”

Section: Discussionmentioning

confidence: 85%

Management of Clevudine-Resistant Chronic Hepatitis B: A Multicenter Cohort Study

et al. 2017

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“…Nevertheless, Chu et al revealed that the virologic response rate for children, of whom the majority had one mutation, was 37.5% at 24 weeks and 50% at 48 weeks, compared with 7.7 ∼33.3% at 24 weeks and 22.0∼54.5% at 48 weeks for adult patients, although the children had higher baseline HBV DNA load than adults [43]. Lamivudine + adefovir combination therapy has been proven to have a more potent antiviral effect than entecavir monotherapy [71,72]. Even though entecavir has a good effect on initial viral suppression, entecavir alone has a relatively high resistance rate in lamivudine-resistant patients and is considered to be less effective than lamivudine + adefovir combination therapy.…”

Section: Switch Therapy To Entecarvirmentioning

confidence: 99%

Strategy to Overcome Drug Resistance That Develops during Treatment of Chronic Hepatitis B in Children

Hong

Choe

2012

Pediatr Gastroenterol Hepatol Nutr

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Development of antiviral resistance to lamivudine is the most important factor for the treatment failure. It is necessary to establish proper guidelines to overcome drug resistance for children with chronic hepatitis B. Primary treatment with lamivudine should be considered if patients are in immune-clearance phase and have persistently elevated ALT levels more than twice the upper limit of normal value. Before initiating the therapy, careful consideration of the patient's status is required to exclude abnormal liver function tests due to other causes. The treatment option should be carefully decided to suppress the viral replication effectively. To obtain good compliance, clinicians should educate patients and their parents. Appropriate monitoring for virologic breakthrough and genotypic resistance is important in deciding to change the treatment plan. Sequential monotherapy should be avoided and a combination of drugs in other categories is recommended. New antiviral agents, such as entecavir and tenofovir, which have high potency and high genetic barrier, are soon expected to be available for use with children. (Pediatr Gastroenterol Hepatol Nutr 2012; 15: 63∼73)

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“…Twenty patients were consecutively recruited from nine hospitals affiliated with seven universities between February 2010 and February 2011. Previously, we conducted a randomized controlled trial comparing the efficacy of ETV monotherapy versus ADV plus LMV combination therapy in 219 LMV-resistant CHB patients [16]. One hundred and nine patients received ETV 1 mg for 2 years.…”

Section: Methodsmentioning

confidence: 99%

Adefovir and Lamivudine Combination Therapy in Patients with Entecavir-Resistant Chronic Hepatitis B: Antiviral Responses and Evolution of Mutations

et al. 2014

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Objective: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. Methods: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. Results: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log₁₀ IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log₁₀ IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). Conclusions: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

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Adding adefovir vs. switching to entecavir for lamivudine‐resistant chronic hepatitis B (ACE study): a 2‐year follow‐up randomized controlled trial

Cited by 23 publications

References 32 publications

Management of Clevudine-Resistant Chronic Hepatitis B: A Multicenter Cohort Study

Management of Clevudine-Resistant Chronic Hepatitis B: A Multicenter Cohort Study

Strategy to Overcome Drug Resistance That Develops during Treatment of Chronic Hepatitis B in Children

Adefovir and Lamivudine Combination Therapy in Patients with Entecavir-Resistant Chronic Hepatitis B: Antiviral Responses and Evolution of Mutations

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