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Christian Trepo - One of the best experts on this subject based on the ideXlab platform.

  • impact of <B>HepatitisB> B virus rta181v t mutants on <B>HepatitisB> B Treatment failure
    Journal of Hepatology, 2008
    Co-Authors: Stephanie Villet, C Pichoud, Gaetan Billioud, Luc Barraud, Sandra Durantel, Christian Trepo
    Abstract:

    Background/Aims Recent clinical oBservations reported the occurrence of amino acid suBstitutions at position 181 of the HBV polymerase, associated with a viral Breakthrough under lamivudine or adefovir therapy. In this study, we characterized the main variants harBoring the rtA181T/V mutation isolated from 10 consecutive patients who developed lamivudine and/or adefovir resistance. Methods We performed a clonal analysis of the HBV polymerase gene amplified By PCR from serum samples during viral Breakthrough. The main mutants were then tested after transfection of Huh7 cells for their resistance profile to nucleoside analogs. Results Clonal analysis revealed the co-localization on the same HBV genome of rtA181T/V with rtN236T, But not with rtM204V/I mutations following lamivudine, adefovir or lamivudine+adefovir Breakthrough. In cell culture, the rtA181T/V mutation induced a decreased susceptiBility to lamivudine ( Conclusions Our oBservations suggest that a single amino acid change at position rt181 may induce cross-resistance to lamivudine and adefovir. These data emphasize the clinical relevance of genotypic and phenotypic analysis in the management of antiviral drug resistance.

  • Impact of <B>HepatitisB> B virus rtA181V/T mutants on <B>HepatitisB> B Treatment failure.
    Journal of Hepatology, 2008
    Co-Authors: Stephanie Villet, C Pichoud, Gaetan Billioud, Luc Barraud, Sandra Durantel, Christian Trepo, Fabien Zoulim
    Abstract:

    Background/Aims Recent clinical oBservations reported the occurrence of amino acid suBstitutions at position 181 of the HBV polymerase, associated with a viral Breakthrough under lamivudine or adefovir therapy. In this study, we characterized the main variants harBoring the rtA181T/V mutation isolated from 10 consecutive patients who developed lamivudine and/or adefovir resistance. Methods We performed a clonal analysis of the HBV polymerase gene amplified By PCR from serum samples during viral Breakthrough. The main mutants were then tested after transfection of Huh7 cells for their resistance profile to nucleoside analogs. Results Clonal analysis revealed the co-localization on the same HBV genome of rtA181T/V with rtN236T, But not with rtM204V/I mutations following lamivudine, adefovir or lamivudine+adefovir Breakthrough. In cell culture, the rtA181T/V mutation induced a decreased susceptiBility to lamivudine ( Conclusions Our oBservations suggest that a single amino acid change at position rt181 may induce cross-resistance to lamivudine and adefovir. These data emphasize the clinical relevance of genotypic and phenotypic analysis in the management of antiviral drug resistance.

Yasuji Arase - One of the best experts on this subject based on the ideXlab platform.

  • Clearance of <B>HepatitisB> B surface antigen during long-term nucleot(s)ide analog Treatment in chronic <B>HepatitisB> B: results from a nine-year longitudinal study
    Journal of Gastroenterology, 2013
    Co-Authors: Tetsuya Hosaka, Fumitaka Suzuki, Masahiro Kobayashi, Yuya Seko, Yusuke Kawamura, Hitomi Sezaki, Norio Akuta, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase
    Abstract:

    Background Clearance of <B>HepatitisB> B surface antigen (HBsAg) is considered the ultimate goal in chronic <B>HepatitisB> B Treatment. One Treatment option is long-term nucleot(s)ide analog (NA) therapy. We followed a group of long-term NA therapy patients to evaluate the efficacy of this Treatment in promoting clearance and longitudinal declines of HBsAg. Method The study included 791 NA therapy patients who received lamivudine as their first drug. At the Baseline, 442 patients were <B>HepatitisB> B e antigen (HBeAg)+ and 349 were HBeAg−. All analyses were performed after separating the HBeAg+ and HBeAg− cohorts. Cox proportional hazards models were used to determine which factors were associated with HBsAg clearance. Results HBsAg clearance was oBserved in 18 (4.1 %) of the HBeAg+ patients and 20 (5.7 %) of the HBeAg− patients at Baseline, giving seroclearance rates of 6.4 and 6.9 %, respectively, over the nine-year study period. HBsAg clearance was influenced By several independent factors that varied according to HBeAg cohort. For HBeAg+ patients, these included previous interferon therapy, infection with <B>HepatitisB> B virus (HBV) genotype A, a ≥0.5 log IU/mL decline in HBsAg level within six months, and clearance of HBeAg at six months. For HBeAg− patients, these included infection with HBV genotype A, decline in HBsAg at six months, and a Baseline HBsAg level of

  • Clearance of <B>HepatitisB> B surface antigen during long-term nucleot(s)ide analog Treatment in chronic <B>HepatitisB> B: results from a nine-year longitudinal study.
    Journal of Gastroenterology, 2012
    Co-Authors: Tetsuya Hosaka, Fumitaka Suzuki, Masahiro Kobayashi, Yuya Seko, Yusuke Kawamura, Hitomi Sezaki, Norio Akuta, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase
    Abstract:

    Background Clearance of <B>HepatitisB> B surface antigen (HBsAg) is considered the ultimate goal in chronic <B>HepatitisB> B Treatment. One Treatment option is long-term nucleot(s)ide analog (NA) therapy. We followed a group of long-term NA therapy patients to evaluate the efficacy of this Treatment in promoting clearance and longitudinal declines of HBsAg.

Man-fung Yuen - One of the best experts on this subject based on the ideXlab platform.

  • Novel developments of <B>HepatitisB> B: Treatment goals, agents and monitoring tools.
    Expert Review of Clinical Pharmacology, 2019
    Co-Authors: Wai-kay Seto, James Fung, Man-fung Yuen
    Abstract:

    Introduction: Chronic <B>HepatitisB> B (CHB) infection causes consideraBle morBidity and mortality and hence should Be a target for gloBal elimination. In recent years, advances have Been made in unders...

  • <B>HepatitisB> B: Treatment choice and monitoring for response and resistance.
    Expert Review of Gastroenterology & Hepatology, 2016
    Co-Authors: Wai-kay Seto, Man-fung Yuen
    Abstract:

    Despite effective preventive primary prevention with vaccination, many people remain infected with <B>HepatitisB> B virus (HBV) and suffer from its complications. Effective Treatments such as interferon-Based regimens and oral nucleoside/nucleotides have Been developed over the last 30 years, But they are not perfect. Each of the Treatments has its own merits, But none can eradicate HBV from the host. As a result, regular monitoring of the response during Treatment and after Treatment is required. The choice and monitoring of selected Treatments, new potential therapeutic agents, and Treatment options for drug resistance are discussed in this review.

  • extrahepatic effects of nucleoside and nucleotide analogues in chronic <B>HepatitisB> B Treatment
    Journal of Gastroenterology and Hepatology, 2014
    Co-Authors: James Fung, Wai-kay Seto, Man-fung Yuen
    Abstract:

    Oral nucleoside/nucleotide analogues (NAs) are the mainstay of therapy for patients with chronic <B>HepatitisB> B and are generally well tolerated. Despite this, the safety profile of NAs is of paramount importance since the majority of patients will require long-term Treatment. All NAs can potentially affect human DNA polymerase with decrease in mitochondrial DNA, leading to manifestations of mitochondrial toxicity. As a class effect, therefore, NAs can potentially cause extrahepatic conditions, such as myopathy, nephropathy, neuropathy, and lactic acidosis. Indeed, effects on muscles, including myopathy and creatine kinase elevations, have Been descriBed with clevudine and telBivudine use. Both adefovir and tenofovir are associated with dose-dependent nephropathy, predominantly affecting the proximal renal tuBules. Neuropathy appears to Be rare, and most commonly reported in patients receiving comBination therapy with telBivudine and interferon. Increased risk of lactic acidosis has also Been descriBed for those with impaired liver and renal function taking entecavir. Loss of Bone mineral density and hypophosphatemia have Been descriBed with the use of NAs, although the overwhelming studies have Been with human immunodeficiency virus-infected patients. However, not all extrahepatic effects are detrimental. Recent evidence has suggested a potential renal Beneficial effect with the use of telBivudine. The effect of NAs on pregnancy appears to Be minimal for all NAs, with telBivudine and tenofovir having a more favoraBle category B rating. Ongoing pharmacovigilance is essential to identify new and monitor existing extrahepatic effects associated with NA use.

  • Current Antiviral Therapy of Chronic <B>HepatitisB> B: Efficacy and Safety
    Current Hepatitis Reports, 2011
    Co-Authors: Man-fung Yuen, Wai-kay Seto
    Abstract:

    The Treatment of chronic <B>HepatitisB> B is in constant evolution. Interferon, the first agent licensed for chronic <B>HepatitisB> B Treatment, has Been superseded By the growing popularity of nucleoside/nucleotide analogues (NA). However, resistance to these agents is a major challenge. Newer NAs, such as entecavir and tenofovir dipivoxil fumarate, have very low resistance rates and favoraBle safety profiles. Long-term use of these agents can effectively suppress <B>HepatitisB> B virus DNA, leading to decrease in incidence of hepatitic flares, as well as in the development of cirrhosis and hepatocellular carcinoma. The efficacy and safety of various antiviral agents is discussed in this review.

Stephanie Villet - One of the best experts on this subject based on the ideXlab platform.

  • impact of <B>HepatitisB> B virus rta181v t mutants on <B>HepatitisB> B Treatment failure
    Journal of Hepatology, 2008
    Co-Authors: Stephanie Villet, C Pichoud, Gaetan Billioud, Luc Barraud, Sandra Durantel, Christian Trepo
    Abstract:

    Background/Aims Recent clinical oBservations reported the occurrence of amino acid suBstitutions at position 181 of the HBV polymerase, associated with a viral Breakthrough under lamivudine or adefovir therapy. In this study, we characterized the main variants harBoring the rtA181T/V mutation isolated from 10 consecutive patients who developed lamivudine and/or adefovir resistance. Methods We performed a clonal analysis of the HBV polymerase gene amplified By PCR from serum samples during viral Breakthrough. The main mutants were then tested after transfection of Huh7 cells for their resistance profile to nucleoside analogs. Results Clonal analysis revealed the co-localization on the same HBV genome of rtA181T/V with rtN236T, But not with rtM204V/I mutations following lamivudine, adefovir or lamivudine+adefovir Breakthrough. In cell culture, the rtA181T/V mutation induced a decreased susceptiBility to lamivudine ( Conclusions Our oBservations suggest that a single amino acid change at position rt181 may induce cross-resistance to lamivudine and adefovir. These data emphasize the clinical relevance of genotypic and phenotypic analysis in the management of antiviral drug resistance.

  • Impact of <B>HepatitisB> B virus rtA181V/T mutants on <B>HepatitisB> B Treatment failure.
    Journal of Hepatology, 2008
    Co-Authors: Stephanie Villet, C Pichoud, Gaetan Billioud, Luc Barraud, Sandra Durantel, Christian Trepo, Fabien Zoulim
    Abstract:

    Background/Aims Recent clinical oBservations reported the occurrence of amino acid suBstitutions at position 181 of the HBV polymerase, associated with a viral Breakthrough under lamivudine or adefovir therapy. In this study, we characterized the main variants harBoring the rtA181T/V mutation isolated from 10 consecutive patients who developed lamivudine and/or adefovir resistance. Methods We performed a clonal analysis of the HBV polymerase gene amplified By PCR from serum samples during viral Breakthrough. The main mutants were then tested after transfection of Huh7 cells for their resistance profile to nucleoside analogs. Results Clonal analysis revealed the co-localization on the same HBV genome of rtA181T/V with rtN236T, But not with rtM204V/I mutations following lamivudine, adefovir or lamivudine+adefovir Breakthrough. In cell culture, the rtA181T/V mutation induced a decreased susceptiBility to lamivudine ( Conclusions Our oBservations suggest that a single amino acid change at position rt181 may induce cross-resistance to lamivudine and adefovir. These data emphasize the clinical relevance of genotypic and phenotypic analysis in the management of antiviral drug resistance.

Tetsuya Hosaka - One of the best experts on this subject based on the ideXlab platform.

  • Clearance of <B>HepatitisB> B surface antigen during long-term nucleot(s)ide analog Treatment in chronic <B>HepatitisB> B: results from a nine-year longitudinal study
    Journal of Gastroenterology, 2013
    Co-Authors: Tetsuya Hosaka, Fumitaka Suzuki, Masahiro Kobayashi, Yuya Seko, Yusuke Kawamura, Hitomi Sezaki, Norio Akuta, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase
    Abstract:

    Background Clearance of <B>HepatitisB> B surface antigen (HBsAg) is considered the ultimate goal in chronic <B>HepatitisB> B Treatment. One Treatment option is long-term nucleot(s)ide analog (NA) therapy. We followed a group of long-term NA therapy patients to evaluate the efficacy of this Treatment in promoting clearance and longitudinal declines of HBsAg. Method The study included 791 NA therapy patients who received lamivudine as their first drug. At the Baseline, 442 patients were <B>HepatitisB> B e antigen (HBeAg)+ and 349 were HBeAg−. All analyses were performed after separating the HBeAg+ and HBeAg− cohorts. Cox proportional hazards models were used to determine which factors were associated with HBsAg clearance. Results HBsAg clearance was oBserved in 18 (4.1 %) of the HBeAg+ patients and 20 (5.7 %) of the HBeAg− patients at Baseline, giving seroclearance rates of 6.4 and 6.9 %, respectively, over the nine-year study period. HBsAg clearance was influenced By several independent factors that varied according to HBeAg cohort. For HBeAg+ patients, these included previous interferon therapy, infection with <B>HepatitisB> B virus (HBV) genotype A, a ≥0.5 log IU/mL decline in HBsAg level within six months, and clearance of HBeAg at six months. For HBeAg− patients, these included infection with HBV genotype A, decline in HBsAg at six months, and a Baseline HBsAg level of

  • Clearance of <B>HepatitisB> B surface antigen during long-term nucleot(s)ide analog Treatment in chronic <B>HepatitisB> B: results from a nine-year longitudinal study.
    Journal of Gastroenterology, 2012
    Co-Authors: Tetsuya Hosaka, Fumitaka Suzuki, Masahiro Kobayashi, Yuya Seko, Yusuke Kawamura, Hitomi Sezaki, Norio Akuta, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase
    Abstract:

    Background Clearance of <B>HepatitisB> B surface antigen (HBsAg) is considered the ultimate goal in chronic <B>HepatitisB> B Treatment. One Treatment option is long-term nucleot(s)ide analog (NA) therapy. We followed a group of long-term NA therapy patients to evaluate the efficacy of this Treatment in promoting clearance and longitudinal declines of HBsAg.