Mutations in HBV DNA Polymerase Associated With Nucleos(t)ide Resistance Are Rare in Treatment-naive Patients

Vutien, Philip; Trinh, Huy N.; Garcia, Ruel T.; Nguyen, Huy; Levitt, Brian S.; Nguyen, Khanh K.; Silveira, Eduardo; Daugherty, Tami; Ahmed, Aijaz; García, Gabriel; Lutchman, Glen; Nguyen, Mindie H.

doi:10.1016/j.cgh.2013.11.036

Cited by 28 publications

(38 citation statements)

References 31 publications

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“…Finally and to a lesser extent than in HIV, transmission of drug-resistant HBV strains has already been reported [49][50][51]. They seem restricted to 3TC although mutations conferring resistance to other anti-HBV agents have occasionally been seen [52,53]. Transmission of 3TC-resistant HBV has been documented in up to 5% of newly diagnosed HBV persons in some studies [54].…”

Section: Lamivudine As Only Active Anti-hbv Agent In Hiv-hbv Coinfectionmentioning

confidence: 94%

Advances in treating drug-resistant hepatitis B virus in HIV-infected patients

Soriano

Mendoza

Peña

et al. 2014

Expert Opinion on Pharmacotherapy

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Section: Lamivudine As Only Active Anti-hbv Agent In Hiv-hbv Coinfectionmentioning

confidence: 94%

Advances in treating drug-resistant hepatitis B virus in HIV-infected patients

Soriano

Mendoza

Peña

et al. 2014

Expert Opinion on Pharmacotherapy

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“…Therefore, rtV191I mutation may be the new resistance site to LAM. Since rt224I/V has never been reported before [13,[22][23][24][25][26], further observation of these patients might address the question whether these mutations are associated with other nucleoside analogue resistance or affect the outcome of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Given the lower prevalence of HBV drug-resistant in the naïve patients, some investigators suggested that routine testing for resistant mutation before initiating antiviral therapy is not necessary [13,17] But further research has revealed that tyrosine-methionineaspartate-aspartate (YMDD) mutations also exist in patients with CHB infection without LAM treatment [18,19], Zhao Y et al [20] used INNO-LiPA assay to detect mutations in HBV DNA polymerase associated with NAs resistance in 269 treatment-naive patients with CHB and found 24 patients (8.9%) with detected mutations in HBV DNA polymerase. In this study we found 60 patients (16.8%) with pre-existing resistant mutations in HBV chronically infected patients.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in the RT region of the polymerase gene at amino acid location rtA181T/V, rtM204V/I/S, rtN236T, and rtM250I/V were interpreted as primary resistance mutations, while rtL80V/I, rtI169T, rtV173L, rtL180M, rtT184A/C/G/S, rtS202C/G/I , rt214, rtQ215S , rtL217P, rtL229M, rtI233V and rtN238H were considered as secondary or compensatory mutations [12][13][14]. Rt214, rt215, rt221 and rt238 mutations could reduce the antiviral efficacy of ADV, and was considered as "minor mutations" or "propose mutations" [3,15,16].…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis B virus pre-existing drug resistant mutation is related to the genotype and disease progression

Wang

Han

Duan

et al. 2017

J Infect Dev Ctries

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Introduction: Previous studies have indicated that the drug-resistant mutations of hepatitis B virus (HBV) are a major obstacle to antiviral therapy. However, it is still unclear whether there are pre-existent resistance mutations in patients with HBV infection and the relationship between drug-resistant mutation, genotypes, and progression of hepatitis B disease. Methodology: A total of 357 treatment-naïve patients with HBV infection were involved in this retrospective study. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. Results: Lamivudine (LAM) resistance was detected in 8 patients (3.7%) with chronic hepatitis B (CHB), 13 (11.7%) patients with liver cirrhosis (LC), and 6 (21.4%) patients with hepatocellular carcinoma (HCC). Adefovir(ADV)-resistant mutations were detected in 10 (4.6%) patients with CHB, 15 (13.5%) patients with LC and 4 (14.5%) patients with HCC. Both LAM and ADV resistant mutations were detected in 2 patients (0.9%) with CHB, 1 patient (0.9%) with LC and 1 patient (3.6%) with HCC. Significant differences (p <0.01) were observed in the drug-resistance rates among patients with CHB, LC and HCC. Meanwhile, all the drug-resistant mutations were found in patients with HBV genotype C. Conclusions: This study demonstrated higher risk of pre-existing drug-resistant mutations in patients with HBV genotype C comparing to patients with HBV genotype B. Likewise, increasing prevalence of pre-existing drug-resistant mutations was shown, alongside with the progression of the disease.

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“…Such variability is likely to occur due to the differences in the methods applied to determine the mutation in the HBV pol gene, overall study design, and study population (20)(21)(22)(23)(24)(25)(26)(27)(28)(29). However, Sayan et al, mentioned that the direct sequencing approach could limit the detection of primary resistance mutations (11).…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

Molecular Characterization of Drug Resistance in Hepatitis B Viruses Isolated from Patients with Chronical Infection in Turkey

et al. 2018

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Background: Hepatitis B virus (HBV) has a high mutation rate due to its unusual replication strategy leading to the production of a large number of virions with single and double mutations. The mutations, in turn, are associated with the development of drug resistance to nucleos(t)ide analogs (NUCs) in patients before and during NUCs therapy. Objectives: The current study aimed at investigating the molecular characterization of HBV in Turkish patients with chronic hepatitis B (CHB) infection. Methods: Polymerase chain reaction (PCR) amplification and direct sequencing procedures were used to analyze mutations. The detected drug resistance mutations were divided into the nucleos(t)ide analogs primary, partial, and compensatory resistance groups. The amino acid substitutions of hepatitis B surface antigen (HBsAg) were categorized into antiviral drug -associated potential vaccine -escape mutations (ADAPVEMs) and typical HBsAg amino acid substitutions, which included hepatitis B hyperimmunoglobulin (HBIg) -selected escape mutation, vaccine escape mutation, hepatitis B misdiagnosis, and immune -selected amino acid substitutions. Results: The number of patients included in the study was 528 out of which 271 (51.3%) were treatment -naive and 351 (66.3%) were hepatitis B e antigen (HBeAg) -negative. Moreover, 325 (61.6%) were males with a mean age of 38 years (range: 18 -69). Primary, partial, and compensatory resistance to NUCs was reported in 174 (32.9%) patients. Six different ADAPVEM motifs were determined in both treatment -naive and treatment -experienced patients, namely, sF161L/rtI169X, sE164D/rtV173L, sL172L/rtA181T, sL173F/rtA181V, sS195M/rtM204V, and sS196L/rtM204I. The prevalence of ADAPVEMs and typical HBsAg escape mutations was 5.3% (n = 28) and 34.8% (n = 184), respectively. Conclusions:The analysis of drug resistance should constitute a fundamental part of the follow -up period of patients with CHB undergone treatment with NUCs. The surveillance of development of drug resistance mutations, while receiving treatment for hepatitis B is of paramount importance to monitor and control the emerging resistance.

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Mutations in HBV DNA Polymerase Associated With Nucleos(t)ide Resistance Are Rare in Treatment-naive Patients

Cited by 28 publications

References 31 publications

Advances in treating drug-resistant hepatitis B virus in HIV-infected patients

Advances in treating drug-resistant hepatitis B virus in HIV-infected patients

Hepatitis B virus pre-existing drug resistant mutation is related to the genotype and disease progression

Molecular Characterization of Drug Resistance in Hepatitis B Viruses Isolated from Patients with Chronical Infection in Turkey

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