Antiviral Resistance Mutations and Genotype-Associated Amino Acid Substitutions in Treatment-Naïve Hepatitis B Virus-Infected Individuals from the Indian Subcontinent

Ismail, Ashrafali Mohamed; Samuel, Prasanna; Eapen, C.E.; Kannangai, Rajesh; Abraham, Priya

doi:10.1159/000323521

Cited by 40 publications

(44 citation statements)

References 82 publications

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“…This mutation is needed to be confirmed for resistance. We did not detect the mutations rtI233V and rtS213T related to adefovir and entecavir/lemivudine respectively which were reported by Ismail et al [6] from treatment naive Indian patients. Again, the small sample seize may be the reason for this discrepancy.…”

Section: Discussioncontrasting

confidence: 63%

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Analysis of resistant mutations in reverse transcriptase domain of hepatitis B virus from patients from Islamabad, Pakistan

Mahmood¹,

Anwar²

2017

JUMD

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Aim:To explore nucleoside/nucleotide analogues resistance mutations in hepatitis B virus (HBV) reverse transcriptase (RT) domain from non-responder Pakistani patients. Methods: Blood samples were taken from 20 chronic HBV patients who were non-responders to different nucleoside/nucleotide analogues. HBV DNA was extracted and a fragment of genome including RT domain was sequenced. The sequence was aligned with wild type HBV sequences and compared with resistant mutations in the RT domain. Results: Resistant mutations were detected in samples of 13 (65%) patients who were non-responders to more than one drug. The mutations were found at amino acid positions rt80, rt135, rt169, rt173, rt180, rt181, rt184 and rt204 and rt248. Mutations rtY135S and rtN248H were detected from 13 (65%) and 12 (60%) samples respectively. Mutations rtL180M and rtA181V were present in 6 (30%) samples, rtM204V and rtV173L in 5 (25%) samples while rtI169P, rtL80G and rtT184Y were identified from 3 (15%), 2 (10%) and 1 (5%) sample respectively. Conclusion: Nucleoside /Nucleotide analogues resistant mutations rt135, rtL180M, rtA181V, rtM204V, rtV173L and rtN248H are frequent in HBV strains isolated from non-responder Pakistani patients while mutations rtI169P, rtL80G and rtT184Y are also present in low proportion. Key words:Hepatitis B virus, resistant mutations, reverse transcriptase, nucleos(t)ide analogues, Pakistan ABSTRACTArticle history:

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Section: Discussioncontrasting

confidence: 63%

“…The sequences were also analyzed for HBV resistance drugs [3][4][5] . Since the HBV genome does not have a proofreading ability, the mutations occur with a very high frequency of occurrence [6] . This antiviral resistance is the most significant factor causing treatment failure in chronic HBV infections [7] .…”

Section: Analysis Of the Sequencesmentioning

confidence: 99%

Analysis of resistant mutations in reverse transcriptase domain of hepatitis B virus from patients from Islamabad, Pakistan

Mahmood¹,

Anwar²

2017

JUMD

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“…Almost all these mutations were reported previously and there were also many other mutations in this segment of RT gene which had been identified by earlier reports (41, 42). The well known mutation rtV173L observed in two cases (3.2%), which is a compensatory mutation and could be selected in lamivudine-resistant patients due to an enhanced replication phenotype (43).…”

Section: Discussionmentioning

confidence: 65%

Genotyping and Mutation Pattern in the Overlapping MHR Region of HBV Isolates in Southern Khorasan, Eastern Iran

et al. 2016

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BackgroundHepatitis B virus, with 8 known distinct genotypes, is one of the most serious health problems which results to liver injuries. The surface gene of Hepatitis B virus completely overlaps with the polymerase gene. Mutations in the RT gene result in changes in the overlapping hepatitis B surface antigen.ObjectivesThe present study aimed to evaluate the genotypes and prevalence of mutations in a segment of S and RT gene in HBV isolates in Southern Khorasan, Iran.MethodsThis was a population-based study comprising 5,235 randomized samples for HBV screening. A nested-polymerase chain reaction (PCR) test was followed by direct sequencing, and the sequences blast with present sequences of NCBI database for genotyping. Alignment and phylogenic analysis was performed using MEGA-6 software, and mutation pattern of this segment was finally surveyed in Bioedit software.ResultsThe mean age was 39.07 ± 14.04 years, with 52.2% female and 47.8% male. All isolates belonged to HBV genotype D, sub-genotype D1. The most amino acid substitutions of surface protein were Q129H (34.42%) and A168V (8.2%), other escape mutants observed in this study were P127L/T, S117G, T125M, S143L, D144E and E164D. In the RT gene, Q149K was the most frequently identified amino acid substitution (9.83%), followed by L122F (8.19%), N118D/T (6.55%), L157M (4.91%), and H124Y (3.27%).ConclusionsThis finding represents an ongoing dominancy of HBV genotype D in Eastern Iran, corresponding to other parts of Iran. There were a lot of variations in the S gene leading to an escape mutation, some of which affected the corresponding area of the RT region.

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“…In recent studies conducted with non-treated patients in different countries, it was shown that the frequencies of HBV strains which had clinically important drug resistance mutation (NA resistance) were between 0.5% and 1% (17,18,19,20,21,22,23,24,25 (29) evaluated 30 CHB patients who were not previously treated and they determined HBV NA resistance-related mutations in 3 of them (10%).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus Carrying Drug-resistance Compensatory Mutations in Chronically Infected Treatment-naive Patients

Altındiş¹,

Aslan²,

Köroğlu³

et al. 2016

vhd

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ÖZObjective: The prevalence of hepatitis B virus (HBV) is highly variable throughout the world. Geographical regions are classified according to the prevalence of hepatitis B surface antigen in the general population as high (>8%), moderate (2-7%), and low endemicity (<2%). Turkey has a moderate endemicity level of HBV infection which is a serious health problem. Currently, there are various nucleos(t)ide analogues with anti-HBV activity and they are mostly used in the treatment of chronic hepatitis B (CHB) and cirrhosis. The risk of drug resistance increases because these drugs are still being used as monotherapy. It has been reported that HBV drug resistance-related mutations can occur also in patients who are classified as treatment-naive and who have not received any oral anti-HBV treatment. Materials and Methods:This prospective and descriptive epidemiological study aimed to determine the genotype/subgenotypes of HBV and to investigate the drug resistance mutations in treatment-naive CHB patients. The study included 149 CHB patients who had no chronic coinfections, and have not received treatment for CHB infection. In 53 of the samples collected from the patients, the amount of viral DNA was enough for sequence analysis to search for drug resistance. BigDyeTM Terminator Cycle Sequencing Kit (Applied Biosystems, Foster City, Calif., USA) was used for sequencing of the serum samples from these patients and drug resistance mutations were determined and genotype/ subgenotype detection was performed. Results:The mean viral load value was calculated as 9.84x10 6 , and there was no primary drug resistance in any of these 53 samples which were sequenced. There were compensatory resistance-related amino acid changes in 19 samples. Genotype D was determined as HBV in all cases. Conclusion:The early detection of drug resistance-related mutations can be important in determination of treatment protocol, and prevention of unnecessary drug use, complications, and economic loses.

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Antiviral Resistance Mutations and Genotype-Associated Amino Acid Substitutions in Treatment-Naïve Hepatitis B Virus-Infected Individuals from the Indian Subcontinent

Cited by 40 publications

References 82 publications

Analysis of resistant mutations in reverse transcriptase domain of hepatitis B virus from patients from Islamabad, Pakistan

Analysis of resistant mutations in reverse transcriptase domain of hepatitis B virus from patients from Islamabad, Pakistan

Genotyping and Mutation Pattern in the Overlapping MHR Region of HBV Isolates in Southern Khorasan, Eastern Iran

Hepatitis B Virus Carrying Drug-resistance Compensatory Mutations in Chronically Infected Treatment-naive Patients

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