YMDD mutations in patients with chronic hepatitis B untreated with antiviral medicines

ZhongMin, Huang; Huang, Qiwen; Qin, Yaqin; He, Yong; Qin, Houji; Zhou, Yiao-Nan; Xu, Xiang; Huang, Meijin

doi:10.3748/wjg.v11.i6.867

Cited by 33 publications

(61 citation statements)

References 19 publications

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“…The rate of YMDD mutations in patients after one year of LAM therapy was 14-32% (7,8,10,16,20). However, the rate of YMDD mutation after one year LAM therapy of the present study was 12.12%, which is slightly lower than a previous study (15). Allen (8) classified YMDD mutations into two categories: rtM204V + rtL180M and rtM204I, and the study suggested that rtM204V and rtL180M do not occur alone.…”

Section: Discussioncontrasting

confidence: 53%

“…This motif, which is localized in the polymerase structural region C area, is the combing and functioning site of Lamivudine (a nucleoside antiviral). Lamivudine-resistant HBV strains with YMDD mutations have been implemented in the failure of chronic hepatitis B treatment (15). It has been reported that the seminested PCR products of the DNA polymerase gene exhibit intergenotypic divergence of ≥4%, which is in accordance (5,(14)(15)(16), and the effect of the genotype on LAM therapy is different (5,17,18).…”

Section: Introductionmentioning

confidence: 87%

“…Lamivudine-resistant HBV strains with YMDD mutations have been implemented in the failure of chronic hepatitis B treatment (15). It has been reported that the seminested PCR products of the DNA polymerase gene exhibit intergenotypic divergence of ≥4%, which is in accordance (5,(14)(15)(16), and the effect of the genotype on LAM therapy is different (5,17,18). Therefore, the present study aimed to investigate the correlation between feature and genotype with regard to the YMDD mutation in chronic hepatitis B patients following LAM therapy.…”

Section: Introductionmentioning

confidence: 99%

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Association between clinical features and YMDD mutations in patients with chronic hepatitis B following lamivudine therapy

Yuan

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the correlation between feature and genotype with regard to the tyrosine-methionine-aspartate-aspartate (YMDD) mutation in chronic hepatitis B patients after lamivudine (LAM) therapy. A total of 30 patients with chronic hepatitis B were recruited, who underwent one year of LAM therapy. The patients' alanine aminotransferase (ALT) level and hepatitis B envelope antigen (HBeAg) seroconversion were evaluated, hepatitis B virus (HBV) DNA was genotyped using a new genotyping method and YMDD mutations were analyzed prior to treatment and at 6 and 12 months after LAM treatment. Furthermore, the secondary protein structure of the HBV DNA polymerase gene (P gene) was analyzed. Following treatment, the results suggested that LAM therapy improved ALT normalization. There was no correlation between clinical effects and ALT level before treatment. After 12 months treatment, the rate of HBeAg loss increased and the rate of HBeAg seroconversion decreased linearly with the rise of baseline ALT level. While ALT normalization and HBeAg seroconversion were highest in patients with HBV genotype B, HBeAg loss and HBVDNA loss were highest in those with genotype C. The effect was predominant in genotype D. No YMDD mutations were identified prior to 6 months of LAM therapy. The rate of YMDD mutations after 12 months LAM therapy was 12.12%. Two patients with rtM204V + rtL180M belonged to genotype C and another patient with rtL180M alone belonged to genotype D. The turn of secondary protein structure of P gene changed to β sheet when a rtM204V mutation occurred, and no change of secondary protein structure was associated with the rtL180M mutation. Thus, the present results indicate that one year of LAM therapy is able to improve ALT normalization. Long-term LAM therapy may induce YMDD mutation and drug resistance.

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Section: Discussioncontrasting

confidence: 53%

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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Association between clinical features and YMDD mutations in patients with chronic hepatitis B following lamivudine therapy

Yuan

et al. 2016

Experimental and Therapeutic Medicine

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“…Lamivudine has revolutionized the treatment of chronic hepatitis B. Lamivudine-resistant mutations in the YMDD motif of polymerase gene were detected in lamivudine treated and untreated patients with chronic hepatitis B [14,[17][18][19] . Clinical breakthrough was observed 2 wk-7 mo after the emergence of YMDD mutations [8][9][10] , causing considerable morbidity and mortality in those patients [20][21][22][23][24] .…”

Section: Discussionmentioning

confidence: 99%

Comparison of ligase detection reaction and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B

Wang¹,

Xie²,

Zhang³

et al. 2008

WJG

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“…Several factors may contribute such as noncompliance, inefficient conversion from the prodrug to its active metabolite, inadequate phosphorylation within the hepatocytes or underdosing of the dr ug. Some patients failing to respond initially to treatment may already harbour a resistant mutant prior to the start of therapy [90,91] . Underdosing is particularly an issue with adefovir treatment as the 10 mg dose was chosen for safety reasons.…”

Section: Management Of Treatment Failures To Nucleos(t)ide Analoguesmentioning

confidence: 99%

Future prospectives for the management of chronic hepatitis B

Leemans

Janssen

Man³

2007

WJG

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Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately one million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. T h e a m o u n t o f v ira l re p l ic a t io n re f le c t e d in t he viral load (HBV-DNA) plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory (interferons) and antiviral suppressants (nucleoside and nucleotide analogues) all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the crossresistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion: chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determine the best treatment for those failing treatment.

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YMDD mutations in patients with chronic hepatitis B untreated with antiviral medicines

Cited by 33 publications

References 19 publications

Association between clinical features and YMDD mutations in patients with chronic hepatitis B following lamivudine therapy

Association between clinical features and YMDD mutations in patients with chronic hepatitis B following lamivudine therapy

Comparison of ligase detection reaction and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B

Future prospectives for the management of chronic hepatitis B

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