YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study

Tan, Youwen; Gao, Ge; Zhao, Wei; Gan, Jing; Zhao, Yun; Niu, Zhi-Lin; Zhang, Dongjun; Chen, Li; Xue, Yan; Yang, Liying

doi:10.1016/s1413-8670(12)70319-7

Cited by 17 publications

(22 citation statements)

References 20 publications

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“…No mutation was noted in 33.2% of the cases. It was reported that the infection rates of mutant virus in antiviral treatment naïve patients could be influenced by the mutant virus prevalence in the society [7, 8]. Where there is no available data for HBV mutation rates, the mutation rates in the chronic HBV patients visiting hospital might be utilized to postulate the infection rates of mutant virus in antiviral treatment naïve patients.…”

Section: Discussionmentioning

confidence: 99%

“…Zhao et al [7] reported the rate of natural YMDD mutations in Western China as 15.56% from 270 antiviral non-treated (treatment naïve) chronic hepatitis B patients. Moreover, Tan et al [8] found natural YMDD mutations in 23.3% of 1,042 patients recruited from six centers in China. They posited that the natural existence of YMDD mutant strains was associated with a larger HBV load in chronic hepatitis B patients.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Reverse Transcriptase Gene Mutations in the Hepatitis B Virus at a University Hospital in Korea

Lee

Jeon

2014

Ann Lab Med

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BackgroundMost mutations in the reverse transcriptase (RT) gene of the hepatitis B virus (HBV) are related to resistance to antiviral agents. Cross-sectional studies on the mutations of this gene are rare. Thus, we analyzed the mutation patterns of RT genes and their biochemical parameters.MethodsFrom 2009 to 2012, 301 blood specimens from patients with chronic hepatitis B at Daegu Catholic University Medical Center were retrospectively analyzed for the RT gene sequence of HBV, ALT, hepatitis B e antigen (HBeAg), and HBV DNA. The mutation patterns of the RT gene were compared with the biochemical parameters.ResultsOf the 301 patients, 100 (33.2%) had no RT gene mutations. The remaining showed the following mutation patterns: rtM204I/V (50.2%), rtL180M (39.2%), and rtA181T/V (19.6%). Combined mutations were found in 146 cases (48.5%). Of these, the combination of amino acid changes at rt180+rt204 (49.3%) was most frequently detected, followed by rt181+rt236 (11.0%) and rt173+rt180+rt204 (9.6%). In the mutated group, HBV DNA and HBeAg positive rates were significantly higher (P<0.05 for both). Phenotypic analysis showed that lamivudine resistance was most frequently detected (34.6%), followed by adefovir resistance (15.6%). Multidrug resistance was detected in 48 cases (15.9%). The adefovir-resistant group had a higher proportion of cases with HBV loads greater than 2,000 IU/mL.ConclusionsWe found correlations between the mutation status of the RT domain and biochemical parameters such as HBV DNA and HBeAg positive rate. The presence of RT gene mutations could therefore be utilized to predict clinical status.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of Reverse Transcriptase Gene Mutations in the Hepatitis B Virus at a University Hospital in Korea

Lee

Jeon

2014

Ann Lab Med

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“…180. kodonda oluşan L180M/C mutasyonunun ise tek başına direnç oluşumunda yeterli olmadığı, ancak rtM204V/I/S ile birlikte bulunduğunda hem replikasyonu hem de LVD direncini artırdığı gösterilmiştir 8 . Yapılan çalışmalarda YVDD mutasyonuna hemen daima L180M mutasyonunun eşlik ettiği, YIDD tipi mutasyonların ise tek başına da görülebileceği bildirilmektedir [10][11][12] . Çalışmamızda da dizi analizi ile YVDD mutasyonu bir örnekte L180M ve S202G mutasyonları ile bir arada bulunmuştur.…”

Section: Discussionunclassified

Detection of Resistance Mutations in Chronic Hepatitis B Patients Receiving Antiviral Therapy for Over One Year

Aydoğan¹,

Ergünay²,

Balaban³

et al. 2013

Mikrobiyol Bul

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Primary mutations conferring hepatitis B virus (HBV) antiviral resistance and associated secondary/compensatory mutations were investigated in this study by DNA sequencing (SEQ) and two commercial Line Probe Assays (LiPAs) (Inno-Lipa HBV DRv2 and Inno-Lipa HBV DRv3, Innogenetics, Belgium). A total of 71 subjects under follow-up for chronic hepatitis B and receiving lamivudine (LVD) therapy for one year or longer at the Hacettepe University Faculty of Medicine, Department of Internal Medicine, Gastroenterology Unit were included in the study with informed consent. Male to female ratio and mean age was noted as 47/24 and 43 ± 15.8 (age range: 13-71) years, respectively. Twenty samples with low HBV DNA levels (mean: 204.6 IU/ml) could not be interpreted by SEQ due to insufficient amplification. All samples with a positive consensus PCR were further analysed via LiPAs, as directed by the manufacturer. Thus a total of 51 and 56 samples could be evaluated via SEQ and LiPA assays, respectively. In 13 of the 51 (25.5%) samples by SEQ and in 9 of 56 (16%) samples by LiPAs, primary and compensatory mutations associated with resistance were identified. Multiple mutations that comprise L180M + M204I in four and L180M + M204V in one sample and single mutations (M204I) in three samples were identified by SEQ. In one sample which had multiple mutations associated with LVD resistance single mutations (S202G, N236T) associated with entecavir resistance and in two other such samples mutations associated with adefovir resistance were detected by SEQ. Also, in three samples amino acid substitution at position rt215 (QÆS) as alone and in one sample with multiple mutations were observed via SEQ. In five of nine samples primary and compensatory multiple mutations (L180M + M204I in one sample, L80I + L180M + M204I in two samples, L80I/V + M204I in one sample) and primary single mutations associated with LVD resistance (M204I/V) in four samples were detected by Inno-Lipa HBV DRv2. Two different mutations (G202, ILFM184) were observed in two samples with multiple mutations associated LVD resistance via Inno-Lipa HBV DRv3. However, mutation at position rt184 was evaluated as a weak positive. Any mutation associated with adefovir resistance was not detected by LiPA. As a result, SEQ and LiPAs displayed comparable performances for the detection of HBV drug resistance mutations. We suggested that for the evaluation of discordant results, it should be better to test consecutive serum samples.

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“…The most common combination mutations include amino acid changes at rt180 + rt204, rt181 + rt236 and rt173 + rt180 + rt204 [63]. The methionine at rt204 is part of the YMDD active site in box C; the rt173, rt180 and rt181 positions are in box B; and rt236 is in box D. In addition to these most common mutations, several mutations have been associated with NRTI treatment [60,64–68].…”

Section: Importance Of Different Domains Motifs and Residuesmentioning

confidence: 99%

Unveiling the Roles of HBV Polymerase for New Antiviral Strategies

Clark

2015

Future Virol.

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Infection with HBV is common worldwide, with over 350 million chronic carriers. Chronic HBV infection is associated with cirrhosis and hepatocellular carcinoma. All currently available oral antivirals are directed against the HBV polymerase enzyme, a reverse transcriptase. HBV polymerase contains several important domains and motifs which define its functions and reveal ways to further target it. This enzyme executes many functions required for the HBV replication cycle, including viral RNA binding, RNA packaging, protein priming, template switching, DNA synthesis and RNA degradation. In addition, HBV polymerase must interact with host proteins for its functions. Future therapeutics may inhibit not only the DNA synthesis steps which are carried out by the reverse transcriptase domain (as all current antivirals do) but other domains, functions and interactions which are essential to the HBV replication cycle.

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YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study

Abstract: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.

Cited by 17 publications

References 20 publications

Analysis of Reverse Transcriptase Gene Mutations in the Hepatitis B Virus at a University Hospital in Korea

Analysis of Reverse Transcriptase Gene Mutations in the Hepatitis B Virus at a University Hospital in Korea

Detection of Resistance Mutations in Chronic Hepatitis B Patients Receiving Antiviral Therapy for Over One Year

Unveiling the Roles of HBV Polymerase for New Antiviral Strategies

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