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Lilly Yuen

Bio: Lilly Yuen is an academic researcher from Royal Melbourne Hospital. The author has contributed to research in topics: Hepatitis B virus & Hepatitis B. The author has an hindex of 18, co-authored 44 publications receiving 1126 citations. Previous affiliations of Lilly Yuen include The Chinese University of Hong Kong & University of Melbourne.
Topics: Hepatitis B virus, Hepatitis B, HBsAg, Genotype, Virus

Papers
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Journal ArticleDOI
TL;DR: Prevention of resistance requires the adoption of strategies that not only effectively control HBV replication, but also prevent the emergence of ADAPVEMs.
Abstract: A high rate of viral turnover, combined with an error-prone polymerase, results in a very high frequency of mutational events during HBV replication. Not surprisingly, particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antivirals), readily select out new 'escape' mutants. The introduction of nucleoside/nucleotide analogue (NA) therapy for chronic hepatitis B has witnessed the emergence of antiviral drug resistance as the major factor limiting drug efficacy. Furthermore, because of the overlap of the viral polymerase and envelope reading frames in the HBV DNA genome, NA resistance-associated mutations selected in the catalytic domains of the polymerase frequently result in important changes to the neutralizing antibody-binding domains of the hepatitis B surface antigen, including the emergence of antiviral drug-associated potential vaccine escape mutants (ADAPVEMs). The public health significance of ADAPVEMs is considerable in terms of the global programme for control of hepatitis B via universal infant immunization. Thus, prevention of resistance requires the adoption of strategies that not only effectively control HBV replication, but also prevent the emergence of ADAPVEMs.

102 citations

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TL;DR: Results suggest that coselection of rtL80V/I and rtM204I/V occurs because the former compensates for the loss of replication efficiency associated with the acquisition of LMV resistance, particularly in the case of rm204I.
Abstract: Long-term lamivudine (LMV) treatment of chronic hepatitis B almost inevitably engenders viral resistance. Mutations that result in the replacement of the methionine at position 204 of the deoxynucleoside triphosphate-binding site of the hepatitis B virus (HBV) reverse transcriptase (rt) by isoleucine, valine, or (rarely) serine (rtM204I/V/S) confer high-level resistance to LMV but reduce replication efficiency. The subsequent selection or coselection of secondary mutations that partially restore replication efficiency is common and may influence drug resistance. Genotyping has shown that LMV treatment can select for HBV rtL80V/I mutants, but their prevalence and phenotype have not been documented. Analysis of a large sequence database revealed that rtL80V/I occurred almost exclusively in association with LMV resistance, and 85% of these isolates encoded rtL80I. Coselection of rtL80V/I occurred in 46% of isolates in which LMV resistance was attributable to rtM204I but only 9% of those in which resistance was attributable to rtM204V. Moreover, rtL80V/I did not occur in HBV genotype A isolates but occurred at similar frequencies in genotype B, C, and D isolates. In vitro phenotyping showed that although the rtL80I mutant by itself replicated less efficiently and was hypersensitive to LMV compared to the replication efficiency and sensitivity of its wild-type parent, the presence of rtL80I enhanced the replication efficiency of rt204I/V mutants without significantly affecting LMV resistance. Molecular modeling revealed that rt80 does not interact directly with the enzyme's substrates. Collectively, these results suggest that coselection of rtL80V/I and rtM204I/V occurs because the former compensates for the loss of replication efficiency associated with the acquisition of LMV resistance, particularly in the case of rtM204I.

101 citations

Journal ArticleDOI
TL;DR: HBV genotypes C can be differentiated into 2 subgroups--namely, genotype Ce and genotype Cs--that have different epidemiological distributions and virological characteristics.
Abstract: BACKGROUND: We aimed to investigate the characteristics of hepatitis B virus (HBV) genotype C subgroups in Hong Kong and their relationship with HBV genotype C in other parts of Asia. METHODS: Full-genome nucleotide sequences of 49 HBV genotype C isolates from Chinese patients with chronic hepatitis B were compared with the sequences of 69 HBV genotype C isolates and 12 non-genotype C isolates in the GenBank database. Phylogenetic analysis was performed to define the subgroups of HBV genotype C on the basis of >4% heterogeneity of the entire HBV genome. RESULTS: HBV in 80% of patients in Hong Kong belonged to a subgroup predominantly found in Southeast Asia (Vietnam, Thailand, Myanmar, and southern China) designated as HBV genotype "Cs," and HBV in the remaining 20% of patients belonged to another subgroup, predominantly found in the Far East (Korea, Japan, and northern China), designated as HBV genotype "Ce." Overall, the mean+/-SD nucleotide sequence difference between HBV genotype Cs and HBV genotype Ce was 4.2%+/-0.3%. When HBV genotype Cs and HBV genotype Ce were compared among patients in Hong Kong, HBV genotype Cs was associated with a higher tendency to develop basal core promoter mutations (80% vs. 50%; P=.14), a higher prevalence of C at nucleotide 1858 (95% vs. 0%; P<.001), and a lower prevalence of precore stop codon mutations (5% vs. 50%; P=.002). CONCLUSIONS: HBV genotype C can be differentiated into 2 subgroups--namely, genotype Ce and genotype Cs--that have different epidemiological distributions and virological characteristics.

100 citations

Journal ArticleDOI
TL;DR: The current theories of the origin and evolution of HBV are discussed and a model that includes cross-species transmissions and subsequent recombination events on a genetic backbone of genotype C HBV infection is proposed.
Abstract: Members of the family Hepadnaviridae fall into two subgroups: mammalian and avian. The detection of endogenous avian hepadnavirus DNA integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. The nonprimate mammalian members of the Hepadnaviridae include the woodchuck hepatitis virus (WHV), the ground squirrel hepatitis virus, and arctic squirrel hepatitis virus, as well as a number of members of the recently described bat hepatitis virus. The identification of hepatitis B viruses (HBVs) in higher primates, such as chimpanzee, gorilla, orangutan, and gibbons that cluster with the human HBV, as well as a number of recombinant forms between humans and primates, further implies a more complex origin of this virus. We discuss the current theories of the origin and evolution of HBV and propose a model that includes cross-species transmissions and subsequent recombination events on a genetic backbone of genotype C HBV infection. The hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the HBV for the completion of its life cycle. The origins of this virus remain unknown, although some recent studies have suggested an ancient African radiation. The age of the association between HDV and HBV is also unknown.

91 citations

Journal ArticleDOI
TL;DR: A model for the origin and evolution of HBV that involves multiple cross-species transmissions and subsequent recombination events on a background of genotype C HBV infection is proposed.

77 citations


Cited by
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Journal ArticleDOI
TL;DR: It is important to continue basic research into HBV replication and pathogenic mechanisms to identify new therapeutic targets, develop novel antiviral agents, design combination therapies that prevent drug resistance, and decrease the incidence of complications of CHB.

659 citations

Journal ArticleDOI
01 Oct 2009-Stroke
TL;DR: It was found that rates of ipsilateral and any-territory stroke (+/−TIA), with medical intervention alone, have fallen significantly since the mid-1980s, with recent estimates overlapping those of operated patients in randomized trials, however, current medical interventionalone was estimated at least 3 to 8 times more cost-effective.
Abstract: Significant advances in vascular disease medical intervention since large randomized trials for asymptomatic severe carotid stenosis were conducted (1983–2003) have prompted doubt over current expectations of a surgical benefit. In this systematic review and analysis of published data it was found that rates of ipsilateral and any-territory stroke (+/−TIA), with medical intervention alone, have fallen significantly since the mid-1980s, with recent estimates overlapping those of operated patients in randomized trials. However, current medical intervention alone was estimated at least 3 to 8 times more cost-effective. In conclusion, current vascular disease medical intervention alone is now best for stroke prevention associated with asymptomatic severe carotid stenosis given this new evidence, other cardiovascular benefits, and because high-risk patients who benefit from additional carotid surgery or angioplasty/stenting cannot be identified.

633 citations

Journal ArticleDOI
TL;DR: The natural history of hepatitis B virus infection including the viral biology, the clinical course of infection and the role of the immune response is discussed.
Abstract: Hepatitis B virus infection represents a major global health problem. Currently, there are more than 240 million chronically infected people worldwide. The development of chronic hepatitis B virus-mediated liver disease may lead to liver fibrosis, cirrhosis and eventually hepatocellular carcinoma. Recently, the discovery of the viral entry receptor sodium taurocholate cotransporting polypeptide has facilitated new approaches for a better understanding of viral physiopathology. Hopefully, these novel insights may give rise to the development of more effective antiviral therapy concepts during the next years. In this review, we will discuss the natural history of hepatitis B virus infection including the viral biology, the clinical course of infection and the role of the immune response.

459 citations

Journal ArticleDOI
TL;DR: There is a need to standardize nomenclature relating to hepatitis B antiviral resistance, and to define genotypic, phenotypesic, and clinical resistance to NA therapy.

443 citations

Journal ArticleDOI
TL;DR: The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with H beAg‐positive and HBeAg‐negative CHB, providing new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker.

393 citations