Analysis of potential antiviral resistance mutation profiles within the HBV reverse transcriptase in untreated chronic hepatitis B patients using an ultra-deep pyrosequencing method

Çıftçı, Sevgi; Çakıris, Aris; Akyüz, Filiz; Pınarbaşı, Binnur; Abacı, Neslihan; Dinçer, Erdinç; Badur, Selim; Kaymakoğlu, Sabahattin; Ustek, Duran

doi:10.1016/j.diagmicrobio.2014.01.005

Cited by 16 publications

(11 citation statements)

References 35 publications

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“…I169T, A181T/V, T184A/C/F/G/I/L/M/S, A194T, S202C/G/I, M204I/V/S, N236T, M250I/L/V) or secondary/compensatory mutations (i.e. L80I/V, V173L, L180M) [ 19 , 20 ] were found in these mutations. Within 43 samples, 35 of them (81.40%) had single amino acid substitution, 7 patients (16.28%) had two amino acids substitution, and 1 patient (2.33%) had three amino acid substitutions.…”

Section: Resultsmentioning

confidence: 99%

Pre-Existing Mutations in Reverse Transcriptase of Hepatitis B Virus in Treatment-Naive Chinese Patients with Chronic Hepatitis B

Wang

et al. 2015

PLoS ONE

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High rate of viral replication and lacking of proofreading activity in hepatitis B virus (HBV) polymerase lead to the generation of mutations in HBV virus. Mutations in the reverse transcriptase (RT) region of HBV polymerase are demonstrated to be strongly associated with drug resistance during antiviral treatment. However, the presence of mutations as well as its clinical significance in treatment-naïve hepatitis patients (defined as pre-existing mutations) need to be further investigated. In the present study, a total of 168 serum samples from treatment-naive chronic hepatitis B (CHB) patients were collected, and the RT region of HBV polymerase was sequenced. The results showed that pre-existing mutations in the RT region of HBV polymerase were detected in 43 of 168 (25.6%) treatment-naive CHB patients within which there were no well-characterized primary nucleotide analogs (NAs) resistance sites. Three dominant sites at rt191, rt207 and rt226 were found mutant in 7(16.28%), 8(18.60%), and 14(32.56%) samples respectively among these 43 patients. No significant correlation was found between pre-existing mutations and gender, age, HBV genotype, ALT, HBeAg or HBV DNA loads. However, patients with pre-existing RT mutations under HBeAg sero-negative status exhibited decreased HBV DNA loads, which contributed to the decreased HBV DNA loads in the total HBeAg sero-negative patients. The above investigation indicated that there was a prevalence of pre-existing mutations in RT region of HBV polymerase which might affect the serum HBV DNA level in treatment-naive CHB patients. Its effects on the occurrence of NAs resistance and the prognosis after treatment need to be further investigated.

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Section: Resultsmentioning

confidence: 99%

Pre-Existing Mutations in Reverse Transcriptase of Hepatitis B Virus in Treatment-Naive Chinese Patients with Chronic Hepatitis B

Wang

et al. 2015

PLoS ONE

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“…Nükleozid/nükleotid analogları ile ilişkili mutasyonlar en çok A, B, C ve D bölgelerinde gelişir. Bu mutasyonlar başlıca primer ilaç mutasyonları (rtI169T, rtA181T/V, rtT184A/C/F/G/I/L/M/S, rtA194T, rtS202C/G/I, rtM204I/V/S, rtN236T, rtM250I/L/V) ve kompensatuvar mutasyonlar (rtL80I/V, rtV173L, rtL180M) olmak üzere iki grupta toplanırlar (22,23) . Lamivudin için 5 farklı direnç paterni; rtM204I, rtL180M + rtM204I, rtL180M + rtM204V, rtV173L + rtL180M + rtM204V, rtL80V/I + rtL180M + rtM204I mevcuttur (24) .…”

Section: Discussionunclassified

Detection of Resistance Mutations in Chronic Hepatitis B Patients Receiving Lamivudine Therapy Using Molecular Method

Kırdar¹,

Yaşa²,

Aydın³

et al. 2016

TMCD

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“…9 P area coding polymerase (pol) enzyme in HBV genome are divided into 7 sub-zones (A, B, C, D, E, F and G). The mutations regarding NA primarily develop in A, B, C and D sub-groups and two groups are of clinical significance: 1 st group: primary resistence mutations (rtI169T, rtA181T/ 10,11 In the HBV genom organization, overlapping position of polymerase (pol) and surface (S) genes can lead to amino acid changes in NA drug resistance mutations and HBsAg protein. Thus, HBV strains escaping from antibodies developed with HBV vaccination can appear due to NA treatments.…”

Section: Abstract: Chronic Hepatitis B Children Antiviral Resistanmentioning

confidence: 99%

Investigation of antiviral resistance and escape mutations in children with naive chronic hepatitis B patients and their parents

et al. 2018

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Tokgöz Y, Terlemez S, Sayan M, Kırdar S. Investigation of antiviral resistance and escape mutations in children with naive chronic hepatitis B patients and their parents. Turk J Pediatr 2018; 60: 514-519. In this study, it was aimed to scan the resistance to nucleoside analogs in naive pediatric patients with chronic hepatitis B treatment and their parents and the rate of accompanying possible escape mutations. A total of 34 children who did not receive any treatment regarding chronic hepatitis B and 19 parents who caused vertical transmission or acquired transmission from father were involved in the study. Serological tests concerning hepatitis B virus and transaminases in conjunction with viral load were studied. HBV genotypes, subgenotypes were determined by surface gene sequencings. The gene mutations coding polymerase (pol) for resistance against nucleoside analogs and escape mutations in the genes coding surface (S) proteins were analyzed with PCR method. All cases were genotype D. Only one pediatric patient was D2; the rest of all pediatric patients and their parents were genotype D1. Resistance was not identified against nucleoside analogs in any children or their parents. HBsAg escape mutations determined in the chronic hepatitis B patients were 18.8% (10 case). It can be speculated with this results that the resistance may not be considered as a problem in the preference of nucleoside analogs in treatment of naive children. Nevertheless, escape mutations were seen as high in both children and parents as well. Since it interests public health on a large scale, advanced studies and evaluation of vaccination escape mutations` rate in broad case series and their follow up are of great importance in the determination of health policies with regard to hepatitis B infection control.

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Analysis of potential antiviral resistance mutation profiles within the HBV reverse transcriptase in untreated chronic hepatitis B patients using an ultra-deep pyrosequencing method

Cited by 16 publications

References 35 publications

Pre-Existing Mutations in Reverse Transcriptase of Hepatitis B Virus in Treatment-Naive Chinese Patients with Chronic Hepatitis B

Pre-Existing Mutations in Reverse Transcriptase of Hepatitis B Virus in Treatment-Naive Chinese Patients with Chronic Hepatitis B

Detection of Resistance Mutations in Chronic Hepatitis B Patients Receiving Lamivudine Therapy Using Molecular Method

Investigation of antiviral resistance and escape mutations in children with naive chronic hepatitis B patients and their parents

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