ArticleJournal of virology2010
Identification and characterization of clevudine-resistant mutants of hepatitis B virus isolated from chronic hepatitis B patients.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial.Clinical and molecular hepatology · 2021Trial
- Susceptibility of Drug Resistant Hepatitis B Virus Mutants to Besifovir.Biomedicines · 2022Article
- Identification and Characterization of Besifovir-Resistant Hepatitis B Virus Isolated from a Chronic Hepatitis B Patient.Biomedicines · 2022Article
- A novel piperazine derivative that targets hepatitis B surface antigen effectively inhibits tenofovir resistant hepatitis B virus.Scientific reports · 2021Article
- ATI-2173, a Novel Liver-Targeted Non-Chain-Terminating Nucleotide for Hepatitis B Virus Cure Regimens.Antimicrobial agents and chemotherapy · 2020Article
- Potential resistant mutations within HBV reverse transcriptase sequences in nucleos(t)ide analogues-experienced patients with hepatitis B virus infection.Scientific reports · 2019Observational
- Intracellular interleukin-32γ mediates antiviral activity of cytokines against hepatitis B virus.Nature communications · 2018Article
- Resistance mutations of hepatitis B virus in entecavir-refractory patients.Hepatology communications · 2017Article
- Anti-hepatitis B virus (HBV) response of imiquimod based toll like receptor 7 ligand in hbv-positive human hepatocelluar carcinoma cell line.BMC infectious diseases · 2017Article
- The efficacy of tenofovir-based therapy in patients showing suboptimal response to entecavir-adefovir combination therapy.Clinical and molecular hepatology · 2016Article
- Hepatitis B virus reverse transcriptase - Target of current antiviral therapy and future drug development.Antiviral research · 2015Review
- Substitution at rt269 in Hepatitis B Virus Polymerase Is a Compensatory Mutation Associated with Multi-Drug Resistance.PloS one · 2015Article
- A randomized, open-label study comparing low-dose clevudine plus adefovir combination therapy with clevudine monotherapy in naïve chronic hepatitis B patients.Hepatology international · 2014Article
- Emerging antivirals for the treatment of hepatitis B.World journal of gastroenterology · 2014Review
- The impact of the hepatitis B virus polymerase rtA181T mutation on replication and drug resistance is potentially affected by overlapping changes in surface gene.Journal of virology · 2014Article
- Management of chronic hepatitis B infection: current treatment guidelines, challenges, and new developments.World journal of gastroenterology · 2014Review
- Molecular diagnosis and treatment of drug-resistant hepatitis B virus.World journal of gastroenterology · 2014Review
- Noncompetitive inhibition of hepatitis B virus reverse transcriptase protein priming and DNA synthesis by the nucleoside analog clevudine.Antimicrobial agents and chemotherapy · 2013Article
- Virological Response and Muscular Adverse Events during Long-Term Clevudine Therapy in Chronic Hepatitis B Patients.Hepatitis monthly · 2013Article
- Long-term treatment outcomes of clevudine in antiviral-naive patients with chronic hepatitis B.World journal of gastroenterology · 2012Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clevudine (CLV) is a nucleoside analog with potent antiviral activity against chronic hepatitis B virus (HBV) infection. Viral resistance to CLV in patients receiving CLV therapy has not been reported. The aim of this study was to characterize CLV-resistant HBV in patients with viral breakthrough (BT) during long-term CLV therapy. The gene encoding HBV reverse transcriptase (RT) was analyzed from chronic hepatitis B patients with viral BT during CLV therapy. Sera collected from the patients at baseline and at the time of viral BT were studied. To characterize the mutations of HBV isolated from the patients, we subjected the HBV mutants to in vitro drug susceptibility assays. Several conserved mutations were identified in the RT domain during viral BT, with M204I being the most common. In vitro phenotypic analysis showed that the mutation M204I was predominantly associated with CLV resistance, whereas L229V was a compensatory mutation for the impaired replication of the M204I mutant. A quadruple mutant (L129M, V173L, M204I, and H337N) was identified that conferred greater replicative ability and strong resistance to both CLV and lamivudine. All of the CLV-resistant clones were lamivudine resistant. They were susceptible to adefovir, entecavir, and tenofovir, except for one mutant clone. In conclusion, the mutation M204I in HBV RT plays a major role in CLV resistance and leads to viral BT during long-term CLV treatment. Several conserved mutations may have a compensatory role in replication. Drug susceptibility assays reveal that adefovir and tenofovir are the most effective compounds against CLV-resistant mutants. These data may provide additional therapeutic options for CLV-resistant patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.