Do different lamivudine‐resistant hepatitis B genotypes carry the same risk of entecavir resistance?

Lee, Guan Huei; Aung, Myat Oo; Dan, Yock Young; Lee, Yin Mei; Mak, Belinda; Low, How Cheng; Lim, Kieron; Thwin, Maung Aye; Tan, Poh Seng; Lim, Seng Gee

doi:10.1002/jmv.23392

Cited by 9 publications

(6 citation statements)

References 30 publications

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“…However, in case of ETV utilization in patients with LAM treatment failure, the development of ETV resistance is more to be expected. Recent study by Lee et al [108] (2013) confirm that patients who harbor M204V strains were significantly more prone to ETV resistance than those who harbor other LAM resistance mutational patterns -rtM204I or rtA181T.…”

Section: Mutationsmentioning

confidence: 93%

Clinical implications of hepatitis B virus mutations: Recent advances

Lazarević¹

2014

WJG

125

108

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Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, and of its long-term complications. It is the most variable among DNA viruses, mostly because of its unique life cycle which includes the activity of error-prone enzyme, reverse transcriptase, and the very high virion production per day. In last two decades, numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus. It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools, thus making the monitoring for these mutations a necessity in proper evaluation of patients. The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen (HBsAg), which may lead to evasion of vaccine-induced immunity. However, the emergence of these mutations has not yet raised concern since it was shown that they develop slowly. Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade, particularly in regard to management of resistance to antiviral drugs. In the era of drugs with high genetic barrier for resistance, on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary. Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols.

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Section: Mutationsmentioning

confidence: 93%

Clinical implications of hepatitis B virus mutations: Recent advances

Lazarević¹

2014

WJG

125

108

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“…However, as shown in previous studies, LAM-resistant HBV patients with the rtM204V mutation had the highest risk of developing ETV resistance compared with those with the rtM204I mutation (Lee et al, 2013). In addition, the rtL229F mutation effectively restored the replication capacity of the rtM204I strain compared with the rtL229W/M/V (Ji et al, 2012).…”

Section: Discussionmentioning

confidence: 53%

Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC

Zhou¹,

Chen²,

Chen³

et al. 2014

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Summary. -The long-term benefits of antiviral treatment are limited by the resistance of hepatitis B virus (HBV). However, the effect of interferon (IFN)α treatment on drug-resistant HBVs is so far unknown. We, therefore, investigated the effects of IFN-α inducer poly-IC on the replication of HBV mutants resistant to drugs such as lamivudine (LAM), adefovir dipivoxil (ADV) and entecavir (ETV) in mice. HBV DNA and HBV DNA intermediate (RI) were employed as markers of the virus replication and 2',5'-oligoadenylate synthase (OAS) mRNA as a marker of IFN-α/β induction. Poly-IC inhibited wtHBV replication and increased levels of OAS mRNA. Compared to the wt virus, the capacity of virus replication was reduced in most LAMr and ETVr mutants except those with mutations rtM(204V+L180M+V173L), and was similary in the ADVr mutants except rt(A121V+N236T). The virus replication was reduced after poly-IC treatment with LAMr and ADVr mutants similary to the wt virus. In contrast, ETVr mutants were resistant to the poly-IC treatment. In conclusion, the capacity of HBV replication and the sensitivity to IFN therapy are influenced by drug-resistant mutations. The IFN therapy may effectively inhibit HBV replication in particular in patients with LAMr or ADVr mutations but not in patients with ETVr mutations.Keywords: hepatitis B virus; mutants; drugs; mouse; interferon; poly-IC * Corresponding author. E-mail: htang6198@hotmail.com; phone: +86-28-8542-2650. Abbreviations: ADV = adefovir dipivoxil; ETV = entecavir; HBV = hepatitis B virus; HBeAg = hepatitis B envelope antigen; HCC = hepatocellular carcinoma; IFN = interferon; LAM = lamivudine; LdT = telbivudine; OAS = 2', 5'-oligoadenylate synthase; r = resistant; RI = replication intermediates; rt,RT = reverse transcriptase; TDF = tenofovir disoproxil fumarate

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“…This could be due to different prevalence of baseline rtM204V mutations between Tenney's (37/57) and our (12/22) cohort. In a separate study, we found rtM204V to have a higher risk of entecavir resistance compared with rtM204I mutation (60% vs 0%, p=0.045) 5. This finding may play an important role in patients who are tenofovir-intolerant or develop tenofovir-related nephrotoxicity, hypophosphatemia and Fanconi syndromes, which occurs in up to 13%, 10% and 2% of treated patients, respectively 6 7.…”

mentioning

confidence: 77%