Antiviral drug-resistant HBV

Lok, Anna S.; Zoulim, Fabien; Locarnini, Stephen; Bartholomeusz, Angeline; Ghany, Marc G.; Pawlotsky, Jean‐Michel; Liaw, Yun–Fan; Mizokami, Masashi; Kuiken, Carla

doi:10.1002/hep.21698

Cited by 415 publications

(432 citation statements)

References 78 publications

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“…Since relevant data are limited, further studies should focus on the contribution of viral factors other than genotype to the treatment outcome of existing antiviral agents. Non-naturally occurring mutations in the polymerase gene play an important role in developing resistance to nucleoside or nucleotide analogues [138], but do not appear to have an adverse effect on the outcome of IFN therapy.…”

Section: Naturally Occurring Mutantsmentioning

confidence: 99%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.

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Section: Naturally Occurring Mutantsmentioning

confidence: 99%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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“…While follow-up visits every 3-6 months are recommended when nucleoside-naive patients are initiated on therapy [4,[8][9][10], information shown in Table 6 suggests that a good proportion of the physicians increased the frequency of follow-up visits to ''once a month for patients with suspected resistance. ''…”

Section: Clinical Experience Of Managing Antiviral Resistance In Pracmentioning

confidence: 99%

Patterns of managing chronic hepatitis B treatment-related drug resistance: a survey of physicians in Mainland China, South Korea, Taiwan, and Thailand

et al. 2009

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Purpose The emergence of antiviral resistance can negate the benefits of antiviral therapy in patients with chronic hepatitis B (CHB). This study aimed to assess how physicians in Asia manage suspected antiviral resistance. Methods Randomly selected CHB-treating physicians in Mainland China, South Korea, Taiwan, and Thailand underwent a face-to-face interview. A standardized questionnaire was used to assess how physicians identify, monitor, and manage suspected resistance and its associated medical costs. Results We interviewed 575 physicians from January to May 2008. Most physicians preferred a ''prevention-of-antiviral resistance'' strategy over a ''rescue-once-resistancedevelops'' strategy. Physicians had encountered lamivudine resistance most frequently (96-100% of respondents), Authors contributed equally to the conception and preparation of the manuscript and are listed alphabetically by their last names.

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“…2,3 In addition, the presence of mutations that confer drug resistance often lead to the failure of treatment with nucleos(t)ide analogs. 4 HBV has been classified into eight major genotypes (designated from A to H), on the basis of an intergroup divergence of 8% or more in the full-length nucleotide sequence, and most of the genotypes show a distinct geographic distribution. 5,6 There is evidence that genotypes A and B are associated with higher rates of hepatitis B e antigen (HBeAg) seroconversion than genotypes C and D during treatment with interferon or pegylated interferon.…”

Section: Introductionmentioning

confidence: 99%

“…HBV that carries rtM204I or rtM204V + rtL180M is also resistant to telbivudine in cell culture. 4 The primary mutations that confer resistance to the nucleotide analog adefovir (ADV) are rtN236T and/or rtA181T/V. 4 Resistance to entecavir may be caused by a two-hit mechanism with initial selection of M204V/I mutation followed by the occurrence of rtT184S/A/I/L/F/G, rtS202G/I, or rtM250V.…”

Section: Introductionmentioning

confidence: 99%

“…4 The primary mutations that confer resistance to the nucleotide analog adefovir (ADV) are rtN236T and/or rtA181T/V. 4 Resistance to entecavir may be caused by a two-hit mechanism with initial selection of M204V/I mutation followed by the occurrence of rtT184S/A/I/L/F/G, rtS202G/I, or rtM250V. 11 The frequency of mutations for lamivudine resistance increases with the duration of lamivudine treatment, and reaches cumulative rates of 15%, 38%, 56%, and 67% in years 1, 2, 3, and 4 of treatment, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous detection of hepatitis B virus genotypes and mutations associated with resistance to lamivudine, adefovir, and telbivudine by the polymerase chain reaction-ligase detection reaction

Wang¹,

Xiao²,

Liu³

et al. 2011

Braz J Infect Dis

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Objectives: Detection of mutations associated to nucleos(t)ide analogs and hepatitis B virus (HBV) genotyping are essential for monitoring treatment of HBV infection. We developed a multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) assay for the rapid detection of HBV genotypes and mutations associated with lamivudine, adefovir, and telbivudine resistance in HBV-infected patients. Methods: HBV templates were amplified by PCR, followed by LDR and electrophoresis on a sequencer. The assay was evaluated using plasmids that contained wild-type or mutant HBV sequences and 216 clinical samples. Results: The PCR-LDR assay and sequencing gave comparable results for 158 of the 216 samples (73.1%) with respect to mutation detection and genotyping. Complete agreement between the two methods was observed for all the samples (100%) at codon 180 and codon 204. Concordant results were observed for 99.4% of the 158 samples at codon 181 and 98.7% at codon 236. The genotyping results were completely concordant between the PCR-LDR assay and sequencing. The PCR-LDR assay could detect a proportion of 1% mutant plasmid in a background of wild-type plasmid. Conclusion: The PCR-LDR assay is sensitive and specific for detection of HBV genotypes and drug resistance mutations, and could be helpful for decision making in the treatment of HBV infection.

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Antiviral drug-resistant HBV

Cited by 415 publications

References 78 publications

Role of viral factors in the natural course and therapy of chronic hepatitis B

Role of viral factors in the natural course and therapy of chronic hepatitis B

Patterns of managing chronic hepatitis B treatment-related drug resistance: a survey of physicians in Mainland China, South Korea, Taiwan, and Thailand

Simultaneous detection of hepatitis B virus genotypes and mutations associated with resistance to lamivudine, adefovir, and telbivudine by the polymerase chain reaction-ligase detection reaction

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