Method: ETV resistance: Two or more amino acid substitutions are required across the HBV RT protein to confer resistance to ETV which could occur as a combination of M204I/V with one or more of the following substitutions L80I/V, I163V, I169T, V173L, L180M, A181S/T/V, T184X, A186T, S202C/G/I/R, M250I/V and/or C256S/G.
COLD-PCR Method for Early Detection of Antiviral Drug-Resistance Mutations in Treatment-Naive Children with Chronic Hepatitis B.
Method: All sequences with completely replaced mt were further determined based on an HBV-drug resistance interpretation online tool of Max Planck Institute for Informatics for classical mt, e.g., rtL180M, rtA181V/T, rtT184G/L, rtA194T, rtS202I/G, rtM204I/V, rtN236T, and rtM250I/V, and based on updated references for nonclassical/putative mt, e.g., V207I/M/L,
Hepatitis B virus mutation pattern rtL180M+A181C+M204V may contribute to entecavir resistance in clinical practice.
Abstract: Primary drug resistance mutations such as rtI169T, rtA181T/V, rtT184A/C/F/G/I/L/M/S, rtA194T, rtS202C/G/I, rtM204I/V/S, rtN236T, rt M250I/L/V and rtV173L were not detected in any of the patient samples.
Characterization and Clinical Significance of Natural Variability in Hepatitis B Virus Reverse Transcriptase in Treatment-Naive Chinese Patients by Sanger Sequencing and Next-Generation Sequencing.
PMID: 31189581
2019
Journal of clinical microbiology
Result: Considering that the low sensitivity of Sanger sequencing limited the detection of NAr mutations with a low rate (<20%), 4 classical drug resistance mutations (S202C/G/I, M204I/V/S, N236T, and M250I/L/V) and 12 putative NAr mutations (V207I, S213T, V214A, Q215P/S, L217R, E218D, L229G/V/W/F, I233V, P237H, N/H238D/S/T, Y245H, and S/C256G)
Prevalence of Hepatitis B Virus Infection in Shenzhen, China, 2015-2018.
Introduction: A total of 8 HBV classical mutation sites are conventionally tested for HBV patients in most clinical labs, including M204I/V, L180M, T184A/F/I/L/S, L181T/V, M250I/L/V, M236T, S202G, and V207I.
Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression.
PMID: 29713126
2018
World journal of gastroenterology
Method: For example, using direct sequencing of samples from treatment-naive patients from the United States, Nguyen et al demonstrated that only four (0.9%) of 472 patients were infected with viruses with primary and secondary mutations (rtA181A/S, rtA194S, and rtM250I).
Table: M250I/L
Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China.
PMID: 27792585
2017
Microbial drug resistance (Larchmont, N.Y.)
Abstract: For entecavir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtM204 V/I+T184 substitution or S202G/C (3.66% vs. 2.16%, p < 0.01) and a lower detection rate of rtM204 V/I+M250 V/I/L substitution (0.67% vs. 1.46%, p < 0.01).
Clinical features and viral quasispecies characteristics associated with infection by the hepatitis B virus G145R immune escape mutant.
Result: We also screened several mutations relevant to antiviral resistance, such as I169L, L180M, A181V, T184I, S202C, M204V/I, N236T and M250I in the RT region.
HBV mutation literature information.
PMID: 
2022
Frontiers in microbiology
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