20-fold increase in risk of lamivudine resistance in hepatitis B virus subtype adw

Zöllner, Bernhard; Petersen, Jörg; Schröter, Matthias; Laufs, Rainer; Schoder, Volker; Feucht, Heinz‐Hubert

doi:10.1016/s0140-6736(00)04219-7

Cited by 104 publications

(82 citation statements)

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“…In addition, Akuta et al recently show that there is no difference in the chance of emergence of YMDD mutations between patients with genotypes B and C in long-term follow-up (1). However, another recent study comparing HBV serotype adw (genotype A) with ayw (genotype D) shows that patients with serotype adw have a higher chance of development of YMDD mutations compared to patients with serotype ayw (24). This finding is important since the YMDD mutation rate is apparently higher in Caucasian patients (32%) than in Asian patients (14%), as demonstrated in the 1-year lamivudine trials conducted in the United States and Asia, where genotype A and genotypes B/C, respectively, are commonly found (3,18).…”

Section: Discussionmentioning

confidence: 99%

“…Another aspect that has not been fully studied is the effect of HBV genotypes on the development of YMDD mutations. One study shows that, compared to patients with genotype D, patients with genotype A are more likely to have YMDD mutations (24). Another study with a relatively short period of follow-up shows that there is no difference in the chance of having YMDD mutations between patients with genotypes B and C (6).…”

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Long-Term Follow-Up Study of Chinese Patients with YMDD Mutations: Significance of Hepatitis B Virus Genotypes and Characteristics of Biochemical Flares

et al. 2004

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The efficacy of lamivudine is limited by mutation of the YMDD (tyrosine, methionine, aspartate, aspartate) motif at the region of the reverse transcriptase (rt204), where M is substituted either by valine (YVDD) or isoleucine (YIDD). The chances of YMDD mutations are 14, 38, 57, and 67% by the first, second, third, and fourth years, respectively, according to long-term follow-up studies conducted in Asia (9,12,14). HBV DNA levels and alanine aminotransferase (ALT) levels after the emergence of YMDD mutants are usually lower than pretreatment levels (5,8,10,13). In spite of the fact that YMDD mutants are comparatively less replication competent than wild-type YMDD (4, 15, 17, 19), biochemical flares resulting in hepatic decompensation may occasionally occur (7,12,14).The frequency, severity, and predictive factors for ALT flares have not been fully investigated. Another aspect that has not been fully studied is the effect of HBV genotypes on the development of YMDD mutations. One study shows that, compared to patients with genotype D, patients with genotype A are more likely to have YMDD mutations (24). Another study with a relatively short period of follow-up shows that there is no difference in the chance of having YMDD mutations between patients with genotypes B and C (6).We sought to examine the role of HBV genotypes in the development of virological breakthroughs with YMDD mutations and the frequency, nature, and factors associated with subsequent biochemical flares. MATERIALS AND METHODSA total of 154 patients were recruited for the present study. These patients were originally recruited into three clinical trials NUCB3009, which was continued as trial NUCB3018. The third trial was NUCB4003. The entry criteria for trial NUCB3009/3018 were that patients (i) were Ն16 years old, (ii) were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for at least 6 months, and (iii) had HBV DNA levels of Ն1.4 ϫ 10 6 copies/ml as determined by solution-hybridization assay (Abbott Diagnostics, Chicago, Ill.) and ALT levels of Յ10 times the upper limit of normal (ULN) (8). For entry into trial NUCB4003, patients had to (i) be Ն16 years old; (ii) be positive HBsAg and HBeAg for at least 6 and 3 months, respectively; and (iii) have detectable HBV DNA levels as determined by branched DNA assay (Bayer Corp., Tarrytown, N.Y.; lower limit of detection ϭ 0.7 ϫ 10 6 copies/ml) and ALT levels of between 1.3 and 10 times the ULN (9). All trials were sponsored by GlaxoSmithKline Research Laboratories and were approved by the Ethics Committee, The University of Hong Kong, Hong Kong.Of the 154 patients, 83 patients were given 100 mg of lamivudine daily. Twenty-seven patients were given 25 mg of lamivudine daily for 1 to 3 years, followed by 100 mg of lamivudine daily at the end of the third year. Forty-four patients were given 500 mg of famciclovir three times daily for 12 weeks, followed by 100 mg of lamivudine daily. All patients were maintained on lamivudine up to

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Long-Term Follow-Up Study of Chinese Patients with YMDD Mutations: Significance of Hepatitis B Virus Genotypes and Characteristics of Biochemical Flares

et al. 2004

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“…Recently, lamivudine was approved for the treatment of chronic HBV infection in many regions of the world. Although convenient and well-tolerated, lamivudine's efficacy rate was similar to interferon and prolonged administration of lamivudine was associated with development of resistance [24][25][26][27][28][29][30] . New agents, such as adefovir dipivoxil, offered a promise either alone or in combination with lamivudine in the treatment of individuals who were 'treatment naïve' have developed lamivudine resistance [31][32][33] .…”

Section: Discussionmentioning

confidence: 99%

Oxymatrine therapy for chronic hepatitis B: A randomized double-blind and placebo-controlled multi-center trial

Lu¹,

Zeng²,

Mao³

et al. 2003

WJG

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AIM:To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. METHODS:A randomised double-blind and placebocontrolled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. RESULTS:Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47 % became normal in ALT level, 38.61 % and 31.91 % became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33 % became normal in ALT level, 43.33 % and 39.29 % became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00 % became normal in ALT level, 7.46 % and 6.45 % became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51 % and 57.84 % in the capsule treated patients, and 33.33 % and 50.00 % in the injection treated patients, and 2.99 % and 41.79 % in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77 %, 6.67 % and 8.82 %, respectively. There was no statistically significant difference among them. CONCLUSION:Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

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“…HBV/C is associated with more severe liver diseases than HBV/ B (Kramvis et al, 2008;Sugauchi et al, 2004;Banerjee et al, 2006;Huy et al, 2006;Sakamoto et al, 2006) while contrary studies reported similarity on the risk of HCC development in either HBV/B or HBV/C infection (Kao et al, 2003;Sumi et al, 2003;Yuen et al, 2003Yuen et al, , 2009. Also, patients infected with HBV/D appear to have a higher incidence of HCC (Chan and Sung, 2006) whereas patients with either HBV/C or HBV/D have a lower response rate to treatment with IFN-α compared to those with HBV/A and HBV/B (Zollner et al, 2001). Genotype may also influence the emergence of lamivudine resistance mutations which appear to be more strongly associated with genotype A than genotype D (Wen, 2004).…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel D11 Hepatitis B Surface Antigen Subgenotype in Jeddah, Kingdom of Saudi Arabia

Hadad¹,

Alakilli²,

Rabah³

et al. 2015

Biotechnology

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A B S T R A C T Hepatitis B virus (HBV) infection remains to be a worldwide health problem. In Saudi Arabia, HBV is the most predominant type of hepatitis followed by hepatitis C and hepatitis A while little is known about the molecular epidemiology of the prevalence of HBV genotype/subgenotype particularly in Jeddah. Serum samples were collected from HBV chronic patients and subjected to HBsAg gene amplification. Sequencing and phylogenetic analysis of the entire HBsAg gene sequences revealed that 11 isolates belonged to HBV/D while 4 isolates were associated with HBV/C. Interestingly, HBV/D subgenotypes identified eight HBV/D present isolates belonged to HBV/D1 while three isolates showed a new cluster supporting by a branch with 99% bootstrap value and 4.3-5.8% nucleotide divergence over the entire HBsAg gene from other known subgenotypes D1 to D10, despite they were appearing more related to HBV/D5. The three strains of the new D subgenotype showed unique amino acid sequences consisting of Thr7non, 75Pro in the preS1 gene, 112Ile, 161Gly in the preS2 gene and 196Glu, 197Ala, 238Ser, 259Cys in the S gene. In addition to three amino acid residues in the S gene (373Ile, 374Ala and 381Thr) were specified S118S isolate. Subsequently, it have been verified that HBV/D1 is the most prevalent HBV subgenotype in Jeddah as well as we proposed a novel subgenotype designated HBV/D11. The identification of HBV/D11 novel subgenotypes in the present study suggested that further studies with a large number of subjects in previously examined and unexamined areas may lead to discovering new HBV strain genotypes and/or subgenotypes circulating in Saudi Arabia.

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20-fold increase in risk of lamivudine resistance in hepatitis B virus subtype adw

Cited by 104 publications

References 5 publications

Long-Term Follow-Up Study of Chinese Patients with YMDD Mutations: Significance of Hepatitis B Virus Genotypes and Characteristics of Biochemical Flares

Long-Term Follow-Up Study of Chinese Patients with YMDD Mutations: Significance of Hepatitis B Virus Genotypes and Characteristics of Biochemical Flares

Oxymatrine therapy for chronic hepatitis B: A randomized double-blind and placebo-controlled multi-center trial

Identification of Novel D11 Hepatitis B Surface Antigen Subgenotype in Jeddah, Kingdom of Saudi Arabia

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