The profile of mutational clusters associated with lamivudine resistance can be constrained by HBV genotypes

Svicher, Valentina; Gori, Caterina; Trignetti, Maria; Visca, M.; Micheli, Valeria; Bernassola, Martina; Salpini, Romina; Gubertini, G.; Longo, Roberta; Niero, Fosca; Ceccherini‐Silberstein, Francesca; Sanctis, Giuseppe Maria De; Spanò, A.; Cappiello, Giuseppina; Perno, Carlo Federico

doi:10.1016/j.jhep.2008.07.038

Cited by 42 publications

(46 citation statements)

References 34 publications

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“…The incidence rate of rtL80I mutation (86.36%; 19/22) was also higher than that of rtL80V (13.67%; 3/22). These results were congruent with those of previous reports [27,28]. These data suggest that some of the amino acid positions in the HBV RT region of NAs-treated patients prefer certain mutational patterns.…”

Section: Discussionsupporting

confidence: 92%

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

Qian

Qin

et al. 2016

J Infect Dev Ctries

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Introduction: Antiviral drug-resistance patterns of hepatitis B virus (HBV) mutants are complex and currently partly understood. The aim of this study was to monitor the genotypic resistance profile in patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogues (NAs) in Huzhou, eastern China. Methodology: Serum samples of 139 CHB patients undergoing NA treatment were obtained from Huzhou Central Hospital. The full-length HBV reverse transcriptase regions were amplified and sequenced. The NA resistance mutation positions, including rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtI233, rtN236, and rtM250 were analyzed. Results: Genotypic resistance mutations were detected in 41.72% (58/139) of patients with CHB. Drug resistance mutations were detected at positions rt80, rt173, rt180, rt181, rt194, rt202, rt204, rt236, and rt250, but were not observed at positions rt169, rt184, and rt233. The prevalence of mutations at rtM204 was 54.44% in 90 patients who were treated with lamivudine (LAM) or telbivudine (LDT). RtN236 mutations were detected in 7.14% (2/28) of the patients receiving adefovir (ADV) therapy. Additionally, rtA181 mutations were observed in 4 patients with LAM, ADV, and LDT-based therapy, but not in those patients treated with entecavir (ETV). Among patients who harbored rtM204 combination mutations, rtM204I and rtM204V were significantly associated with rtL80I/V and rtL180M, respectively. Conclusions: The mutation patterns of NA-resistant HBV are complicated in CHB patients in the current clinical setting. Thus, it is necessary to persistently monitor the resistance mutations of HBV for optimizing antiviral therapy strategy and for preventing an outbreak of clinical resistance.

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Section: Discussionsupporting

confidence: 92%

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

Qian

Qin

et al. 2016

J Infect Dev Ctries

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“…Selecting effective therapeutic plans is critically needed due to the reported association of genotype D with high risk of severe liver disease, recurrence, and fulminant hepatitis [2,7]. Fortunately, genotype D influence on driving viral evolution leading to the emergence of resistance mutations under nucleos(t)ide analogues pressure is relatively low [5,14]. Thus considering HBV genotype is crucial for therapeutic decision making whether by interferon or nucleos(t)ide analogues [8].…”

Section: Discussionmentioning

confidence: 99%

“…Hence investigating resistance mutations beforehand is recommended for efficient drug prescription. Moreover, monitoring drug-resistant mutants during nucleos(t)ide analogues treatment is necessary to ensure early detection of potentially emerging mutations before considerable serum viral load increase in the patient occurs [3,5,15]. This necessity is underscored by our findings of detecting multiple resistance mutations in LMV/ADV-treated patients whose therapeutic plans were continued due to lack of awareness of the critical necessity of timely rescue therapy, and hence were at high risk of mutant selection that led to viral breakthrough, and might lead to hepatitis flare, hepatic decompensation and death [3,15].…”

Section: Discussionmentioning

confidence: 99%

“…Viral nucleotide sequences were subtyped using the NCBI Genotyping tool and Bayesian phylogenetic analysis. Predicted protein translations were searched for thirty mutations previously reported as associated with viral resistance against various nucleos(t)ide analogues including rtL80V/I, rtV84M, rtS85A, rtS135Y, rtI169T, rtV173L, rtL180M/C, rtA181T/V/S, rtT184G/A/S, rtA194T, rtS202I/G, rtM204V/I/S, rtV214A, rtQ215S, rtL229V, rtN236T, rtP237H, rtN238T/D and rtM250V/L [3,5,12]. Chi square and Student's t tests were used to analyze mutation distribution among nucleos(t)ide analogues-naïve and -treated patients.…”

Section: Methodsmentioning

confidence: 99%

“…HBV demonstrates a high mutation rate due to its errorprone reverse transcriptase that lacks exonuclease proofreading activity [4]. Hence drug-resistant variants may emerge throughout nucleos(t)ide analogues-based therapy leading to relapse and hepatic decompensation [5,6]. Moreover, the HBV genotype plays an essential role in driving viral evolution [5] as well as response to interferon-based therapy [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Rethinking therapeutic decisions for hepatitis B infection in Syria: insights into molecular monitoring

Habbal

Monem

2012

J Infect Dev Ctries

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Introduction: Hepatitis B virus patients are usually treated in Syria with alpha interferon and nucleos(t)ide analogues. Genotypic viral factors causing inadequate response or relapse following initial response are not routinely investigated. This study aimed to explore and discuss local therapeutic decisions from a molecular perspective. Methodology: Fifty patients with hepatitis B from Syria were tested for HBV genotyping and drug-resistance mutations by DNA sequencing. Results: All patients had genotype D, which is characterized by relatively low response to interferon-based therapy. Drug-resistant viral mutant variants were detected in one fifth of the enrolled patients, and distributed similarly in both nucleos(t)ide analogues-naïve and -treated patients. However, nucleos(t)ide analogues-based therapy was associated with the existence of more mutations and hence increased resistance. Conclusions: Investigating HBV genotypes and drug-resistance mutations to support treatment decisions is critically needed for efficient therapy and patients' survival.

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Discrepancy of potential antiviral resistance mutation profiles within the HBV reverse transcriptase between nucleos(t)ide analogue‐untreated and ‐treated patients with chronic hepatitis B in a hospital in China

Liu

et al. 2011

Journal of Medical Virology

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Little is known about the discrepancy of the potential antiviral resistance mutation profiles within the hepatitis B virus (HBV) reverse transcriptase (RT) between nucleos(t)ide analogue (NA)-untreated and -treated patients with chronic hepatitis B. Full-length HBV RT sequences from 59 NA-treated and 105 NA-untreated Chinese patients were amplified and sequenced. Forty-two potential NA resistance (NAr) mutation sites were screened within these 164 RT sequences. The NAr mutation prevalence and frequency in the NA-treated group were significantly higher than those in the NA-untreated one (P < 0.001, respectively). The classical primary drug resistance and secondary/compensatory mutations were only detected at seven sites (rtL80, rtI169, rtL180, rtA181, rtT184, rtM204, and rtN236) in NA-treated patients. The non-classical putative NAr and pre-treatment mutations were observed at 22 sites (rtT38, rtN/S53, rtL82, rtL/I91, rtN/Y124, rtH126, rtT128, rtN/D134, rtN139, rtR153, rtV191, rtV207, rtS213, rtV214, rtE218, rtY/F221, rtV/I224, rtL229, rtI233, rtN/H238, rtR242, and rtS/C256) in both groups. Substitutions at seven non-classical mutation sites were of interest due to either detection only in patients with virologic breakthrough (rtL82 and rtV214), or potential ties with HBV genotypes (rtV191 and rtL229), or coexistence with rtM204I/V (rtL229), or increased mutation trends after NA-treatment (rtT128, rtV207, and rtN/H238). In conclusion, NA treatment not only constitutes a major selection factor for the primary and secondary/compensatory NAr mutations but also drives the changes of some of the putative NAr mutation sites, most of which are the genotype-independent RT sites (rtL82, rtT128, rtV191, rtV207, rtV214, rtL229, and rtN/H238). Their antiviral resistance potential calls for further investigations.

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The profile of mutational clusters associated with lamivudine resistance can be constrained by HBV genotypes

Cited by 42 publications

References 34 publications

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

Rethinking therapeutic decisions for hepatitis B infection in Syria: insights into molecular monitoring

Discrepancy of potential antiviral resistance mutation profiles within the HBV reverse transcriptase between nucleos(t)ide analogue‐untreated and ‐treated patients with chronic hepatitis B in a hospital in China

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