Prevalence of mutations in HBV DNA polymerase gene associated with nucleos(t)ide resistance in treatment-naive patients with Chronic Hepatitis B in Central China

Zhao, Yumin; Wu, Jianhua; Sun, Lijun; Liu, Guangzhong; Li, Bo; Zheng, Yi; Li, Xiaodong; Jin-hua, Tao

doi:10.1016/j.bjid.2015.12.006

Cited by 18 publications

(22 citation statements)

References 30 publications

(63 reference statements)

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“…Pastor et al [15] detected rtA194T in 1 of 14 treatment-naive patients with chronic HBV infection in Strasbourg, France. In China, Zhao et al [16] detected spontaneous HBV resistance mutations other than rtA194T (such as rtM204V/I, rtL180M, rtT184G, rtS202I) in 8.9% of their treatment-naive group. In studies conducted in Turkey, Sayan et al [17] detected rtA194T mutation in 2.2% of 88 treatment-naive patients with chronic hepatitis B, while Ergünay et al [18] reported rtA194T mutation in 3.3% of 42 treatment-naive patients with chronic HBV infection.…”

Section: Discussionmentioning

confidence: 99%

Detection of Hepatitis B Virus Drug Resistance Mutations by Pyrosequencing Method

Çimentepe¹,

Yıldırım²,

Kömür³

et al. 2019

mjima

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Giriş: Kronik hepatit B virüs (HBV) enfeksiyonun uzun süreli tedavisi sırasında nükleoz(t)id analoglarına karşı ilaç direnci mutasyonlarının gelişmesi tedavi başarısızlığına yol açabilen önemli bir sorundur. Bu çalışmanın amacı kronik hepatit B enfeksiyonu olan hastalarda HBV ilaç direnci gen mutasyonlarının pyrosequencing metodu ile araştırılmasıdır. Gereç ve Yöntem: Kasım 2013 ve Mayıs 2014 tarihleri arasında, kronik hepatit B enfeksiyonu olan 89'u tedavi almayan (naif) ve 48'i tedavi alan toplam 137 hastaya ait serum örnekleri lamivudin (LAM), adefovir, telbivudin (TEL), entekavir (ETV) ve tenofovir (TDF) ile ilişkili ilaç direnç mutasyonlarının tespiti için real-time polimeraz zincir reaksiyonu testi sonrası pyrosequencing metodu (PyroStar HBV Drug Resistance Test, Altona Diagnostics, Germany) ile analiz edilmiştir. Bulgular: Tedavi almayan 89 hastada, TDF'ye duyarlılığı azaltan rtA194T mutasyonu bir (%1,1) olguda bulunmuştur. Tedavi edilen 48 hastada, LAM ve TEL'e ilaç direnci ve ETV'ye karşı da çapraz dirence sebep olan rtM204I mutasyonu bir (%2,1) olguda tespit edilmiştir. Kompansatuvar mutasyon olan rtL180M iki (%4,2) hastada gözlenmiştir. ETV direncini gösteren rtT184S mutasyonu ile birlikte rtM204V'nin varlığı bir (%2,1) hastada tespit edilmiştir. ÖzIntroduction: The development of drug resistance mutations to nucleos(t)ide analogues during long-term therapy for chronic hepatitis B virus (HBV) infection is a major problem that may lead to treatment failure. The aim of this study was to investigate the HBV drug resistance gene mutations in patients with chronic HBV infection by pyrosequencing method. Materials and Methods: Between December 2013 and May 2014, serum samples collected from 137 patients with chronic HBV infection, (89 treatment-naive and 48 treatment-experienced), were analyzed with real-time polymerase chain reaction analysis followed by pyrosequencing (PyroStar HBV Drug Resistance Test, Altona Diagnostics, Germany) for drug resistance mutations associated with lamivudine (LAM), adefovir, telbivudine (TEL), entecavir (ETV), and tenofovir (TDF). Results: Of the 89 treatment-naive patients, one (1.1%) had the rtA194T mutation, associated with reduced susceptibility to TDF. Of the 48 treatment-experienced patients, one (2.1%) had the rtM204I mutation, associated with drug resistance to LAM, TEL, and cross-resistance to ETV. Compensatory mutation rtL180M was observed in two patients (4.2%). The presence of rtM204V combined with rtT184S mutation indicating ETV resistance was detected in one patient (2.1%). Conclusion: The incidence of drug resistance mutations was 8.3% in treatment-experienced and 1.1% in treatment-naive patients. The use of pyrosequencing technology before and during treatment of patients with chronic HBV infection would contribute to the rapid detection of drug resistance mutations. Abstract Mehmet

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Section: Discussionmentioning

confidence: 99%

Detection of Hepatitis B Virus Drug Resistance Mutations by Pyrosequencing Method

Çimentepe¹,

Yıldırım²,

Kömür³

et al. 2019

mjima

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“…Studies have shown that HBV gene resistance mutations are associated with infected HBV genotypes [8,10]. Some scholars believe that HBV C genotype is more prevalent resistant than B genotype [11,12], but some scholars have found that A181T/V mutation, ETV resistance mutation and multidrug resistance mutation is more predominant in C genotype than B genotype, The incidence of M204I and N236T mutation in B genotypes was higher than that of in C genotype [13]. Some scholars believe that the treatment responses of NAs are similar in each genotype, but there are differences among the primary resistance mutations [14].…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of HBV Pre-Existing Mutations and Drug-induced Resistance Mutations in Patients with Hepatitis B Virus-Related Cirrhosis

Wang

Dai

et al. 2019

IGH

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Background: The reported prevalence and necessity of detection of HBV reverse transcriptase (RT) mutation prior to treatment is varied and remains controversial. This study aimed to identify the prevalence of HBV pre-existing gene resistance mutations and compare the difference between pre-existing mutations and drug-induced resistance mutations in patients with hepatitis B virus-related cirrhosis.Methods: 180 patients with hepatitis B virus-related cirrhosis which included 68 patients with virological breakthrough and 112 treatment-naive cirrhosis patients were retrospectively enrolled. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. One-way ANOVA analysis was performed in the comparison among different groups. Ratios difference was compared with the chi-square test.Results: There were 48 patients (48/112, 42.86%) with drug resistance mutations in nucleoside/nucleotide analogues (NAs) treatment-naive group, 59 patients (59/68, 86.76%) showed drug-resistant mutations in the NAs treatment group. The gene resistance mutation patterns in treatment-naive group were mainly rtS213T, rtV214A, 191V/I and rtN/H238T/D, and the types of resistance mutations in the treated group were different. The adefovir (ADV) group: mainly rtA181T/V and rtS213T; lamivudine/ telbivudine (LAM/LDT) group: rtL180M+ rtM204I/V/S and rtM204I/V/S or a complex mutation pattern containing 204 site; entecavir (ETV) group: The drug resistance pattern is the simultaneous presence of multiple site mutations. LAM/LDT sequential ADV group: The variant type was multi-site and resistant to both ADV and LAM.Conclusion: There was a prevalence of pre-existing mutations in RT region of HBV polymerase in patients with hepatitis B virus-related cirrhosis, The mutation pattern is mainly related to LAM and ADV-related compensatory mutations, while the drug-induced mutation pattern is more complicated, mainly related to the antiviral drugs used and there are mainly primary mutations. Patients with cirrhosis should be tested genetic resistance mutation before using antiviral drugs.

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“…Thirdly, the patient may have some treatments with direct anti-HBV activity, however, s/he may be unaware of it. 19 There is no recommendation regarding antiviral resistance scan in naive chronic HBV treatment.…”

Section: Discussionmentioning

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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Prevalence of mutations in HBV DNA polymerase gene associated with nucleos(t)ide resistance in treatment-naive patients with Chronic Hepatitis B in Central China

Cited by 18 publications

References 30 publications

Detection of Hepatitis B Virus Drug Resistance Mutations by Pyrosequencing Method

Detection of Hepatitis B Virus Drug Resistance Mutations by Pyrosequencing Method

Retrospective Analysis of HBV Pre-Existing Mutations and Drug-induced Resistance Mutations in Patients with Hepatitis B Virus-Related Cirrhosis

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

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