Telbivudine for the management of chronic hepatitis B virus infection

Matthews, S. James

doi:10.1016/j.clinthera.2007.12.032

Cited by 51 publications

(48 citation statements)

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“…This is different from the result for LAM, where rtL80I was shown to be more sensitive to LAM than the WT (Warner et al, 2007). Although LDT is structurally similar to LAM (Matthews, 2007), the difference between these two drugs must contribute to the sensitivity of the mutations. Our results indicate that rtL80I and rtL80V may not only serve as replication complementary mutations to rtM204I, but also contribute to the LDT resistance directly.…”

Section: Resistant Mutations and Hbv Quasispecies In Ldt Therapycontrasting

confidence: 54%

“…It is a complementary mutation, which does not affect the sensitivity of HBV to LAM resistance but compensates partially for the loss of replication efficiency caused by the acquisition of rtM204I/V (Warner et al, 2007). The detection of rtL80I/V in LDT resistance patients has also been reported previously but was not found to be as widespread as during LAM therapy (Lai et al, 2007;Matthews, 2007;Standring et al, 2006). In this study, mutations rtL80I and rtL80V were detected in three out of four viral breakthrough patients, emphasizing the importance of rtL80I and rtL80V in the development of LDT resistance.…”

Section: Resistant Mutations and Hbv Quasispecies In Ldt Therapysupporting

confidence: 50%

“…Mutants rtL80I and rtL80V have been reported in LDTresistant patients previously (Lai et al, 2007;Matthews, 2007;Standring et al, 2006). These mutants were found in three out of the four viral breakthrough patients (Fig.…”

Section: Dynamics Of Na-resistant Mutations During Treatmentmentioning

confidence: 99%

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Resistant mutations and quasispecies complexity of hepatitis B virus during telbivudine treatment

Yin

Wei

et al. 2015

Journal of General Virology

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Ultra-deep pyrosequencing (UDPS) was used to analyse the dynamics of quasispecies and resistant mutations during telbivudine (LDT) treatment of hepatitis B patients. Twenty-six HBeAg-positive chronic hepatitis B patients were treated with LDT for a period of 104 weeks and were characterized as 16 responders, six partial responders and four viral breakthrough patients based on hepatitis B virus (HBV) DNA levels. The plasma samples were subjected to UDPS of the reverse transcriptase (RT) region of HBV. Mutations rtM204I, rtL80I and rtL80V were detected in at least three of the four viral breakthrough patients, indicating the significant roles of the mutations in resistance to LDT. The degree of complexity of viral quasispecies remained in a steady state in the absence of selection pressure, but increased after the LDT treatment. The complexity in the responder group at week 12 was significantly higher than that in the group comprising partial responders and viral breakthrough patients. In vitro replication efficiency analyses showed that the RT mutations had different impacts on HBV replication, with a tendency of rtM204I.rtL80V.rtL80I. Furthermore, double mutations rtL80I/M204I and rtL80V/M204V had replication efficiency similar to that of rtL80I and rtL80V, respectively. Consistent with previous studies, mutation rtM204I was found to be highly resistant to LDT. However, in contrast with their sensitivity to lamivudine, rtL80I and rtL80V were moderately resistant to LDT. Our results indicated that rtL80I and rtL80V may not only serve as replication complementary mutations to rtM204I, but also directly contribute to the LDT resistance.

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Section: Resistant Mutations and Hbv Quasispecies In Ldt Therapycontrasting

confidence: 54%

Section: Resistant Mutations and Hbv Quasispecies In Ldt Therapysupporting

confidence: 50%

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Resistant mutations and quasispecies complexity of hepatitis B virus during telbivudine treatment

Yin

Wei

et al. 2015

Journal of General Virology

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“…Diante desses resultados, Matthews 39 , em revisão de literatura sobre a TBV, ressalta que a terapia combinada não apresenta vantagens em relação à monoterapia com TBV. Uma possível explicação é o fato de ambos os fármacos serem análogos de L-nucleosídeos, de forma que podem competir pelo mesmo sítio de ação 39 .…”

Section: Telbivudinaunclassified

Eficácia do adefovir dipivoxil, entecavir e telbivudina para o tratamento da hepatite crônica B: revisão sistemática

Almeida

Ribeiro

Pádua

et al. 2010

Rev. Soc. Bras. Med. Trop.

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RESUMOIntrodução: A hepatite crônica B é uma das doenças infecciosas mais frequentes no mundo e constitui um grave problema de saúde pública. Métodos: Para avaliar a eficácia dos análogos de núcleosídeo/nucletídeo utilizados no seu tratamento (adefovir dipivoxil, entecavir e telbivudina) foi conduzida uma revisão sistemática de ensaios clínicos randomizados. Foram consultadas, dentre outras, as bases de dados PubMed e LILACS. Resultados: Foram selecionados 29 artigos entre os publicados de janeiro/1970 até dezembro/2009. Conclusões: Todos os análogos de núcleosídeo/nucletídeo apresentam eficácia superior ou similar à lamivudina. O entecavir pode ser indicado para o tratamento da hepatite B crônica como alternativa à lamivudina em pacientes HBeAg positivo e negativo virgens de tratamento, considerando seu baixo potencial de resistência viral. A adição de adefovir à lamivudina apresentou bons resultados em pacientes resistentes à lamivudina. O uso de entecavir e telbivudina nesses pacientes apresenta risco de resistência cruzada. Telbivudina é um dos mais recentes antivirais disponíveis, mas resistência antiviral já documentada representa limitação ao seu uso como opção terapêutica à lamivudina. Eventos adversos aos análogos de núcleosídeo/ nucletídeo foram similares em características, gravidade e incidência quando comparados à lamivudina e placebo. Palavras-chaves: Adefovir dipivoxil. Entecavir. Telbivudina. Hepatite B crônica. Ensaios clínicos randomizados e controlados. ABSTRACTIntroduction: Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health. Methods: A systematic review of randomized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues (adefovir, entecavir and telbivudine) used for the treatment of chronic hepatitis B.

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“…Some studies [5][6][7][8] have indicated that telbivudine treatment has considerable clinical efficacy, was and is well tolerated at all doses (25, 50, 100, 200, 400 and 800 mg/d), with no dose-related or treatment-related clinical or laboratory adverse events. However, other research has shown [9] that 3/680 patients treated with telbivudine presented with myopathy. However, our study is different.…”

Section: Ck (Iu/l) Ldh (Iu/l) Alt (Iu/l) Ast (Iu/l) Ggt (Iu/l) Wbc (× 10mentioning

confidence: 98%

Clinical features of adverse reactions associated with telbivudine

Jin¹,

Zhang²,

Ming-ling³

2008

WJG

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AIM:To analyze the clinical features and risk factors of adverse reactions associated with telbivudine. METHODS: C l i n i c a l d a t a w e r e c o l l e c t e d f r o m cases that presented with serious adverse reactions to telbivudine. We analyzed general information and medicine status, clinical features, results of examination, and misdiagnosis. RESULTS: Out of 105 patients who were treated with telbivudine for hepatitis B in an outpatient department from January, 2007 to January, 2008, five presented with serious adverse drug reactions. Most of these five patients had used other nucleoside analogues in the past. Four were treated with a combination of telbivudine and interferon or another nucleoside analogue, while the other received an increased dose of telbivudine. The main adverse reactions were myalgia and general weakness. This was accompanied by cardiac arrhythmia in one patient, and nervous symptoms in three. Serum creatine kinase was elevated. The rate of misdiagnosis was high. CONCLUSION: The adverse reactions were related to telbivudine, but the biological mechanism of the reactions is not yet clear. Combination therapy with interferon or another nucleoside analogue and a high dose may increase the risk of adverse reactions.

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Telbivudine for the management of chronic hepatitis B virus infection

Cited by 51 publications

References 48 publications

Resistant mutations and quasispecies complexity of hepatitis B virus during telbivudine treatment

Resistant mutations and quasispecies complexity of hepatitis B virus during telbivudine treatment

Eficácia do adefovir dipivoxil, entecavir e telbivudina para o tratamento da hepatite crônica B: revisão sistemática

Clinical features of adverse reactions associated with telbivudine

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