Adefovir Dipivoxil

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Carol L Brosgart - One of the best experts on this subject based on the ideXlab platform.

  • extended treatment with lamivudine and Adefovir Dipivoxil in chronic hepatitis b patients with lamivudine resistance
    Hepatology International, 2011
    Co-Authors: Robert P Perrillo, H W L Hann, Carol L Brosgart, Eugene R Schiff, David Mutimer, Bernard Willems, Nancy Leung, Susan Dixon, Mary Woessner, Lynn D Condreay
    Abstract:

    Purpose We and others have reported that adding Adefovir Dipivoxil (Adefovir) to lamivudine results in virological and biochemical improvement in cases of lamivudine resistance. The current study assessed the efficacy and safety of combined therapy after 104 weeks of combined treatment and analyzed the frequency of persistent lamivudine resistant HBV.

  • long term therapy with Adefovir Dipivoxil for hbeag negative chronic hepatitis b for up to 5 years
    Gastroenterology, 2006
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, Carol L Brosgart, Katyna Borroto Esoda
    Abstract:

    Background & Aims: Treatment with Adefovir Dipivoxil for 48 weeks resulted in clinical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B that was lost when treatment was discontinued. We investigated the efficacy, safety, and resistance profile of Adefovir Dipivoxil treatment for up to 240 weeks. Methods: HBeAg-negative patients were treated double blind with placebo or Adefovir Dipivoxil 10 mg once daily for 48 weeks, followed by Adefovir Dipivoxil from week 49 to 96. At week 97, 125 patients enrolled in a 144-week, open-label phase. Patients received Adefovir Dipivoxil for up to 192 or 240 weeks. Results: Serum hepatitis B virus (HBV) DNA levels were less than 1000 copies per milliliter in 67% of patients, and alanine aminotransferase (ALT) levels normalized in 69% after 240 weeks. After 192 or 240 weeks of treatment, over 83% of patients had improvement in necroinflammation, and over 73% had improvement in fibrosis. Ishak fibrosis scores improved compared with baseline in 35%, 55%, and 71% of patients after 48, 192, and 240 weeks of Adefovir Dipivoxil, respectively. After 240 weeks, the cumulative probability of HBV polymerase mutations was 29%, but the cumulative probability of mutations with virologic resistance was 20% and of mutations, virologic resistance, and ALT elevations was 11%. Slight elevations in creatinine were confirmed in 4 (3%) patients. Conclusions: Treatment with Adefovir Dipivoxil for up to 240 weeks was well tolerated and produced significant, increasing improvement in hepatic fibrosis, durable suppression of HBV replication, normalization of liver enzymes, and delayed development of resistance.

  • safety and efficacy of Adefovir Dipivoxil in patients infected with lamivudine resistant hepatitis b and hiv 1
    Journal of Hepatology, 2006
    Co-Authors: Yves Benhamou, Vincent Thibault, Vincent Calvez, M H Fievet, Annegenevieve Marcelin, Graeme Currie, Chuy G Chang, Lu Biao, Shelly Xiong, Carol L Brosgart
    Abstract:

    BACKGROUND/AIMS: Adefovir Dipivoxil (10 mg once-daily) was added to antiretroviral therapy including lamivudine in 35 HIV/HBV co-infected patients. METHODS: Parameters evaluated included alanine aminotransferase (ALT), HBV DNA and serological markers, HIV-1 RNA, and CD4+ cell count. RESULTS: Twenty-nine patients (83%) completed 144 weeks. Serum HBV DNA declined from a baseline 9.76 log10 copies/mL (median) to 4.68, 5.24, and 5.90 log10 copies/mL at weeks 48, 96, and 144, respectively (P<0.0001 at all time points). Seven patients (25%) achieved HBV DNA<2.3 log10 copies/mL. No Adefovir-associated resistance mutations in HBV DNA polymerase or HIV-1 reverse transcriptase were detected. ALT declined from 81 IU/L (median) at baseline by -16.0, -44.5, and -46.0 IU/L at week 48, 96 and 144, respectively (P=<0.05, respectively), and normalized in 71% of patients (20 of 28) by week 144. Two patients developed antibodies against HB 'e' antigen by week 48. No serious adverse events related to Adefovir Dipivoxil occurred during the study, and HIV-1 RNA and CD4+ cell counts were stable. CONCLUSIONS: Treatment with Adefovir Dipivoxil for 144 weeks was well tolerated and resulted in significant and sustained reductions in HBV DNA and ALT in HIV/HBV co-infected patients. Efficacy increased with treatment duration, with no loss of viral suppression.

  • activity of Adefovir Dipivoxil against all patterns of lamivudine resistant hepatitis b viruses in patients
    Journal of Viral Hepatitis, 2005
    Co-Authors: Chris Westland, Michael Wulfsohn, Carol L Brosgart, William E Delaney, Huiling Yang, Craig S Gibbs, Michael D Miller, Eugene R Schiff, Nicole Lama, Shelly Xiong
    Abstract:

    Summary.  One hundred and thirty-one post-liver transplantation patients with chronic hepatitis B and failing lamivudine therapy with detectable serum hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays or ≥1 × 106 copies/mL by polymerase chain reaction, and elevated alanine transaminase levels despite continuous lamivudine, were enrolled in an open-label study of Adefovir Dipivoxil. The B and C domains of HBV polymerase were sequenced for baseline samples to determine the presence of lamivudine resistance mutations. The results showed that 98% of the samples had tyrosine-methionine-aspartate-aspartate (YMDD) mutations, indicating a strong correlation between the above clinical definition of lamivudine treatment failure and the presence of YMDD mutations. In addition to the rtM204V/I and the rtL180M mutations, the mutation rtV173L was identified in 19% of patients. Four major patterns of lamivudine-resistant HBV were identified: rtL180M + rtM204V (60%), rtV173L + rtL180M + rtM204V (19%), rtM204I (9%) and rtL180M + rtM204I (9%). Treatment with Adefovir Dipivoxil showed similar antiviral efficacy in patients with lamivudine-resistant virus from all four patterns.

  • hepatitis b virus genotypes and virologic response in 694 patients in phase iii studies of Adefovir Dipivoxil
    Gastroenterology, 2003
    Co-Authors: Chris Westland, Stephanos J Hadziyannis, Patrick Marcellin, Carol L Brosgart, William E Delaney, Huiling Yang, Shanshan Chen, Robert G Gish, Craig S Gibbs, Michael D Miller
    Abstract:

    Abstract Background & aims: Hepatitis B virus (HBV) genotype may influence disease progression and antiviral response. We therefore analyzed the frequency and distribution of genotypes in patients from 2 multinational phase III studies of Adefovir Dipivoxil. Antiviral efficacy of Adefovir Dipivoxil 10-mg therapy was examined with respect to HBV genotype, hepatitis B e antigen (HBeAg) serostatus, and race. Methods: HBV genotypes were assigned by phylogenetic analyses of DNA sequences amplified from baseline serum samples (n = 694). Results: Patients from Asia/Oceania were infected predominantly with genotypes B and C, whereas patients from Western European countries were infected predominantly with genotypes A and D. In Mediterranean countries, genotype D was dominant. The most common genotype in North America was C, followed by A, B, and D. Regardless of location, Asian patients were infected predominantly with genotypes B or C, whereas Caucasian patients were infected predominantly with A or D. There were significant differences in the baseline serum HBV-DNA levels of patients infected with different HBV genotypes regardless of HBeAg serostatus. Forty-eight weeks of Adefovir Dipivoxil 10-mg therapy resulted in potent reductions in serum HBV DNA with no significant differences based on genotype, HBeAg status, or race; similarly, there was no statistical difference in HBeAg seroconversion rates between genotypes in these patients. Conclusions: HBV genotypes were distributed asymmetrically with respect to race, geography, and HBeAg status. Forty-eight weeks of Adefovir Dipivoxil therapy resulted in significant decreases in serum HBV-DNA levels in patients regardless of HBV genotype, HBeAg status, or race.

Stephanos J Hadziyannis - One of the best experts on this subject based on the ideXlab platform.

  • long term therapy with Adefovir Dipivoxil for hbeag negative chronic hepatitis b for up to 5 years
    Gastroenterology, 2006
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, Carol L Brosgart, Katyna Borroto Esoda
    Abstract:

    Background & Aims: Treatment with Adefovir Dipivoxil for 48 weeks resulted in clinical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B that was lost when treatment was discontinued. We investigated the efficacy, safety, and resistance profile of Adefovir Dipivoxil treatment for up to 240 weeks. Methods: HBeAg-negative patients were treated double blind with placebo or Adefovir Dipivoxil 10 mg once daily for 48 weeks, followed by Adefovir Dipivoxil from week 49 to 96. At week 97, 125 patients enrolled in a 144-week, open-label phase. Patients received Adefovir Dipivoxil for up to 192 or 240 weeks. Results: Serum hepatitis B virus (HBV) DNA levels were less than 1000 copies per milliliter in 67% of patients, and alanine aminotransferase (ALT) levels normalized in 69% after 240 weeks. After 192 or 240 weeks of treatment, over 83% of patients had improvement in necroinflammation, and over 73% had improvement in fibrosis. Ishak fibrosis scores improved compared with baseline in 35%, 55%, and 71% of patients after 48, 192, and 240 weeks of Adefovir Dipivoxil, respectively. After 240 weeks, the cumulative probability of HBV polymerase mutations was 29%, but the cumulative probability of mutations with virologic resistance was 20% and of mutations, virologic resistance, and ALT elevations was 11%. Slight elevations in creatinine were confirmed in 4 (3%) patients. Conclusions: Treatment with Adefovir Dipivoxil for up to 240 weeks was well tolerated and produced significant, increasing improvement in hepatic fibrosis, durable suppression of HBV replication, normalization of liver enzymes, and delayed development of resistance.

  • long term therapy with Adefovir Dipivoxil for hbeag negative chronic hepatitis b
    The New England Journal of Medicine, 2005
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, S Arterburn, S Xiong
    Abstract:

    Background Treatment with Adefovir Dipivoxil for 48 weeks resulted in histologic, virologic, and biochemical improvement in patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy. Methods One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of Adefovir Dipivoxil or placebo once daily for 48 weeks (ratio, 2:1). After week 48, patients receiving Adefovir Dipivoxil were again randomly assigned either to receive an additional 48 weeks of the drug or to switch to placebo. Patients originally assigned to placebo were switched to Adefovir Dipivoxil. Patients treated with Adefovir Dipivoxil during weeks 49 through 96 were subsequently offered continued therapy. The primary end points were changes in hepatitis B virus (HBV) DNA and alanine aminotransferase levels. Results Treatment with Adefovir Dipivoxil resulted in a median decrease in serum HBV DNA of 3.47 log ...

  • Adefovir Dipivoxil in the treatment of chronic hepatitis B virus infection.
    Expert Review of Anti-infective Therapy, 2004
    Co-Authors: Stephanos J Hadziyannis, George V. Papatheodoridis
    Abstract:

    Adefovir Dipivoxil (Hepsera®, Gilead Sciences) is a prodrug of Adefovir, with potent antiviral activity against hepatitis B virus. Adefovir Dipivoxil therapy, 10 mg daily for 48 weeks, is effective in hepatitis B e antigen-positive and -negative chronic hepatitis B. In hepatitis B e antigen-negative chronic hepatitis B, Adefovir Dipivoxil was recently found to maintain its efficacy even after 3 years of therapy. Adefovir Dipivoxil is effective in patients with compensated or decompensated chronic viral B liver disease, and in pre- and post-transplant hepatitis B virus patients who develop resistance to lamivudine (Epivir®, GlaxoSmithKline). It is well-tolerated and safe even after the third year of long-term therapy, and is associated with low rates of viral resistance. All these characteristics make Adefovir Dipivoxil an important drug for the treatment of hepatitis B virus infection and an excellent candidate for long-term maintenance therapy in chronic viral B liver disease.

  • hepatitis b virus genotypes and virologic response in 694 patients in phase iii studies of Adefovir Dipivoxil
    Gastroenterology, 2003
    Co-Authors: Chris Westland, Stephanos J Hadziyannis, Patrick Marcellin, Carol L Brosgart, William E Delaney, Huiling Yang, Shanshan Chen, Robert G Gish, Craig S Gibbs, Michael D Miller
    Abstract:

    Abstract Background & aims: Hepatitis B virus (HBV) genotype may influence disease progression and antiviral response. We therefore analyzed the frequency and distribution of genotypes in patients from 2 multinational phase III studies of Adefovir Dipivoxil. Antiviral efficacy of Adefovir Dipivoxil 10-mg therapy was examined with respect to HBV genotype, hepatitis B e antigen (HBeAg) serostatus, and race. Methods: HBV genotypes were assigned by phylogenetic analyses of DNA sequences amplified from baseline serum samples (n = 694). Results: Patients from Asia/Oceania were infected predominantly with genotypes B and C, whereas patients from Western European countries were infected predominantly with genotypes A and D. In Mediterranean countries, genotype D was dominant. The most common genotype in North America was C, followed by A, B, and D. Regardless of location, Asian patients were infected predominantly with genotypes B or C, whereas Caucasian patients were infected predominantly with A or D. There were significant differences in the baseline serum HBV-DNA levels of patients infected with different HBV genotypes regardless of HBeAg serostatus. Forty-eight weeks of Adefovir Dipivoxil 10-mg therapy resulted in potent reductions in serum HBV DNA with no significant differences based on genotype, HBeAg status, or race; similarly, there was no statistical difference in HBeAg seroconversion rates between genotypes in these patients. Conclusions: HBV genotypes were distributed asymmetrically with respect to race, geography, and HBeAg status. Forty-eight weeks of Adefovir Dipivoxil therapy resulted in significant decreases in serum HBV-DNA levels in patients regardless of HBV genotype, HBeAg status, or race.

  • Adefovir Dipivoxil for the treatment of hepatitis b e antigen negative chronic hepatitis b
    The New England Journal of Medicine, 2003
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, Michael Wulfsohn, S Xiong
    Abstract:

    Background Adefovir Dipivoxil, a nucleotide analogue, demonstrated clinically significant antiviral activity in patients with chronic hepatitis B in phase 1 and 2 clinical trials. Methods We randomly assigned 185 patients with chronic hepatitis B who were negative for hepatitis B e antigen (HBeAg) to receive either 10 mg of Adefovir Dipivoxil or placebo once daily for 48 weeks in a 2:1 ratio and a double-blind manner. The primary end point was histologic improvement. Results At week 48, 64 percent of patients who had base-line liver-biopsy specimens available in the Adefovir Dipivoxil group had improvement in histologic liver abnormalities (77 of 121), as compared with 33 percent of patients in the placebo group (19 of 57, P<0.001). Serum hepatitis B virus (HBV) DNA levels were reduced to fewer than 400 copies per milliliter in 51 percent of patients in the Adefovir Dipivoxil group (63 of 123) and in 0 percent of those in the placebo group (0 of 61, P<0.001). The median decrease in log-transformed HBV DNA...

Patrick Marcellin - One of the best experts on this subject based on the ideXlab platform.

  • sustained hepatitis b e antigen seroconversion in patients with chronic hepatitis b after Adefovir Dipivoxil treatment analysis of precore and basal core promoter mutants
    Clinical Infectious Diseases, 2008
    Co-Authors: Ichin Wu, Patrick Marcellin, Myron J Tong, Mitchell L Shiffman, Elsa Mondou, David Frederick, Andrea Snow Lampart, J Sorbel, Franck Rousseau, Tingtsung Chang
    Abstract:

    BACKGROUND: This study evaluated the persistence of hepatitis B e antigen (HBeAg) seroconversion (which is considered to be an important therapeutic end point) after Adefovir Dipivoxil treatment. METHODS: Forty-five patients who experienced confirmed HBeAg seroconversion and had a serum hepatitis B virus DNA level < 10(5) copies/mL while receiving 10 mg of Adefovir Dipivoxil in a prior study were enrolled in the present study. At the time of the last dose of Adefovir Dipivoxil (baseline), the median age of the patients was 35 years, 64% were male, 73% were Asian, 27% were white, the median alanine aminotransferase level was 25 IU/L, and the median serum hepatitis B virus DNA level was 3.0 log copies/mL. The median follow-up time was 150 weeks (range, 13-252 weeks). RESULTS: Forty-one patients maintained sustained seroconversion at the last 2 assessments, and 4 experienced seroreversion at weeks 12 (3 patients) and 16 (1 patient) of follow-up. Approximately 50% of patients had a hepatitis B virus DNA level < 1000 copies/mL at the last visit of the study period. Of 13 patients who were viremic and had available samples at the last visit, 11 had basal core promoter and/or precore mutations. Notably, 8 of these 11 patients had basal core promoter and/or precore mutations before Adefovir Dipivoxil therapy despite being HBeAg positive. The median duration of Adefovir Dipivoxil treatment was shorter before seroconversion (48 vs. 108 weeks; P = .03) and longer after seroconversion (41 vs. 22 weeks; P = .02) for patients who experienced sustained seroconversion, compared with the patients who experienced seroreversion. CONCLUSIONS: Prolonged Adefovir Dipivoxil therapy after HBeAg seroconversion appeared to increase the likelihood of sustained HBeAg seroconversion. Most patients who experienced HBeAg seroconversion and had viremia had precore and/or basal core promoter mutants, which usually existed before initiation of Adefovir Dipivoxil therapy.

  • long term therapy with Adefovir Dipivoxil for hbeag negative chronic hepatitis b for up to 5 years
    Gastroenterology, 2006
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, Carol L Brosgart, Katyna Borroto Esoda
    Abstract:

    Background & Aims: Treatment with Adefovir Dipivoxil for 48 weeks resulted in clinical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B that was lost when treatment was discontinued. We investigated the efficacy, safety, and resistance profile of Adefovir Dipivoxil treatment for up to 240 weeks. Methods: HBeAg-negative patients were treated double blind with placebo or Adefovir Dipivoxil 10 mg once daily for 48 weeks, followed by Adefovir Dipivoxil from week 49 to 96. At week 97, 125 patients enrolled in a 144-week, open-label phase. Patients received Adefovir Dipivoxil for up to 192 or 240 weeks. Results: Serum hepatitis B virus (HBV) DNA levels were less than 1000 copies per milliliter in 67% of patients, and alanine aminotransferase (ALT) levels normalized in 69% after 240 weeks. After 192 or 240 weeks of treatment, over 83% of patients had improvement in necroinflammation, and over 73% had improvement in fibrosis. Ishak fibrosis scores improved compared with baseline in 35%, 55%, and 71% of patients after 48, 192, and 240 weeks of Adefovir Dipivoxil, respectively. After 240 weeks, the cumulative probability of HBV polymerase mutations was 29%, but the cumulative probability of mutations with virologic resistance was 20% and of mutations, virologic resistance, and ALT elevations was 11%. Slight elevations in creatinine were confirmed in 4 (3%) patients. Conclusions: Treatment with Adefovir Dipivoxil for up to 240 weeks was well tolerated and produced significant, increasing improvement in hepatic fibrosis, durable suppression of HBV replication, normalization of liver enzymes, and delayed development of resistance.

  • long term therapy with Adefovir Dipivoxil for hbeag negative chronic hepatitis b
    The New England Journal of Medicine, 2005
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, S Arterburn, S Xiong
    Abstract:

    Background Treatment with Adefovir Dipivoxil for 48 weeks resulted in histologic, virologic, and biochemical improvement in patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy. Methods One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of Adefovir Dipivoxil or placebo once daily for 48 weeks (ratio, 2:1). After week 48, patients receiving Adefovir Dipivoxil were again randomly assigned either to receive an additional 48 weeks of the drug or to switch to placebo. Patients originally assigned to placebo were switched to Adefovir Dipivoxil. Patients treated with Adefovir Dipivoxil during weeks 49 through 96 were subsequently offered continued therapy. The primary end points were changes in hepatitis B virus (HBV) DNA and alanine aminotransferase levels. Results Treatment with Adefovir Dipivoxil resulted in a median decrease in serum HBV DNA of 3.47 log ...

  • hepatitis b virus genotypes and virologic response in 694 patients in phase iii studies of Adefovir Dipivoxil
    Gastroenterology, 2003
    Co-Authors: Chris Westland, Stephanos J Hadziyannis, Patrick Marcellin, Carol L Brosgart, William E Delaney, Huiling Yang, Shanshan Chen, Robert G Gish, Craig S Gibbs, Michael D Miller
    Abstract:

    Abstract Background & aims: Hepatitis B virus (HBV) genotype may influence disease progression and antiviral response. We therefore analyzed the frequency and distribution of genotypes in patients from 2 multinational phase III studies of Adefovir Dipivoxil. Antiviral efficacy of Adefovir Dipivoxil 10-mg therapy was examined with respect to HBV genotype, hepatitis B e antigen (HBeAg) serostatus, and race. Methods: HBV genotypes were assigned by phylogenetic analyses of DNA sequences amplified from baseline serum samples (n = 694). Results: Patients from Asia/Oceania were infected predominantly with genotypes B and C, whereas patients from Western European countries were infected predominantly with genotypes A and D. In Mediterranean countries, genotype D was dominant. The most common genotype in North America was C, followed by A, B, and D. Regardless of location, Asian patients were infected predominantly with genotypes B or C, whereas Caucasian patients were infected predominantly with A or D. There were significant differences in the baseline serum HBV-DNA levels of patients infected with different HBV genotypes regardless of HBeAg serostatus. Forty-eight weeks of Adefovir Dipivoxil 10-mg therapy resulted in potent reductions in serum HBV DNA with no significant differences based on genotype, HBeAg status, or race; similarly, there was no statistical difference in HBeAg seroconversion rates between genotypes in these patients. Conclusions: HBV genotypes were distributed asymmetrically with respect to race, geography, and HBeAg status. Forty-eight weeks of Adefovir Dipivoxil therapy resulted in significant decreases in serum HBV-DNA levels in patients regardless of HBV genotype, HBeAg status, or race.

  • Adefovir Dipivoxil for the treatment of hepatitis b e antigen positive chronic hepatitis b
    The New England Journal of Medicine, 2003
    Co-Authors: Patrick Marcellin, Tingtsung Chang, Zachary Goodman, S Xiong, Myron J Tong, William Sievert, Mitchell L Shiffman, Lennox J Jeffers, Michael Wulfsohn, Carol L Brosgart
    Abstract:

    Background In preclinical and phase 2 studies, Adefovir Dipivoxil demonstrated potent activity against hepatitis B virus (HBV), including lamivudine-resistant strains. Methods We randomly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) to receive 10 mg of Adefovir Dipivoxil (172 patients), 30 mg of Adefovir Dipivoxil (173), or placebo (170) daily for 48 weeks. The primary end point was histologic improvement in the 10-mg group as compared with the placebo group. Results After 48 weeks of treatment, significantly more patients who received 10 mg or 30 mg of Adefovir Dipivoxil per day than who received placebo had histologic improvement (53 percent [P<0.001], 59 percent [P<0.001], and 25 percent, respectively), a reduction in serum HBV DNA levels (by a median of 3.52 [P<0.001], 4.76 [P<0.001], and 0.55 log copies per milliliter, respectively), undetectable levels (fewer than 400 copies per milliliter) of serum HBV DNA (21 percent [P<0.001], 39 percent [P<0....

Tingtsung Chang - One of the best experts on this subject based on the ideXlab platform.

  • sustained hepatitis b e antigen seroconversion in patients with chronic hepatitis b after Adefovir Dipivoxil treatment analysis of precore and basal core promoter mutants
    Clinical Infectious Diseases, 2008
    Co-Authors: Ichin Wu, Patrick Marcellin, Myron J Tong, Mitchell L Shiffman, Elsa Mondou, David Frederick, Andrea Snow Lampart, J Sorbel, Franck Rousseau, Tingtsung Chang
    Abstract:

    BACKGROUND: This study evaluated the persistence of hepatitis B e antigen (HBeAg) seroconversion (which is considered to be an important therapeutic end point) after Adefovir Dipivoxil treatment. METHODS: Forty-five patients who experienced confirmed HBeAg seroconversion and had a serum hepatitis B virus DNA level < 10(5) copies/mL while receiving 10 mg of Adefovir Dipivoxil in a prior study were enrolled in the present study. At the time of the last dose of Adefovir Dipivoxil (baseline), the median age of the patients was 35 years, 64% were male, 73% were Asian, 27% were white, the median alanine aminotransferase level was 25 IU/L, and the median serum hepatitis B virus DNA level was 3.0 log copies/mL. The median follow-up time was 150 weeks (range, 13-252 weeks). RESULTS: Forty-one patients maintained sustained seroconversion at the last 2 assessments, and 4 experienced seroreversion at weeks 12 (3 patients) and 16 (1 patient) of follow-up. Approximately 50% of patients had a hepatitis B virus DNA level < 1000 copies/mL at the last visit of the study period. Of 13 patients who were viremic and had available samples at the last visit, 11 had basal core promoter and/or precore mutations. Notably, 8 of these 11 patients had basal core promoter and/or precore mutations before Adefovir Dipivoxil therapy despite being HBeAg positive. The median duration of Adefovir Dipivoxil treatment was shorter before seroconversion (48 vs. 108 weeks; P = .03) and longer after seroconversion (41 vs. 22 weeks; P = .02) for patients who experienced sustained seroconversion, compared with the patients who experienced seroreversion. CONCLUSIONS: Prolonged Adefovir Dipivoxil therapy after HBeAg seroconversion appeared to increase the likelihood of sustained HBeAg seroconversion. Most patients who experienced HBeAg seroconversion and had viremia had precore and/or basal core promoter mutants, which usually existed before initiation of Adefovir Dipivoxil therapy.

  • long term therapy with Adefovir Dipivoxil for hbeag negative chronic hepatitis b for up to 5 years
    Gastroenterology, 2006
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, Carol L Brosgart, Katyna Borroto Esoda
    Abstract:

    Background & Aims: Treatment with Adefovir Dipivoxil for 48 weeks resulted in clinical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B that was lost when treatment was discontinued. We investigated the efficacy, safety, and resistance profile of Adefovir Dipivoxil treatment for up to 240 weeks. Methods: HBeAg-negative patients were treated double blind with placebo or Adefovir Dipivoxil 10 mg once daily for 48 weeks, followed by Adefovir Dipivoxil from week 49 to 96. At week 97, 125 patients enrolled in a 144-week, open-label phase. Patients received Adefovir Dipivoxil for up to 192 or 240 weeks. Results: Serum hepatitis B virus (HBV) DNA levels were less than 1000 copies per milliliter in 67% of patients, and alanine aminotransferase (ALT) levels normalized in 69% after 240 weeks. After 192 or 240 weeks of treatment, over 83% of patients had improvement in necroinflammation, and over 73% had improvement in fibrosis. Ishak fibrosis scores improved compared with baseline in 35%, 55%, and 71% of patients after 48, 192, and 240 weeks of Adefovir Dipivoxil, respectively. After 240 weeks, the cumulative probability of HBV polymerase mutations was 29%, but the cumulative probability of mutations with virologic resistance was 20% and of mutations, virologic resistance, and ALT elevations was 11%. Slight elevations in creatinine were confirmed in 4 (3%) patients. Conclusions: Treatment with Adefovir Dipivoxil for up to 240 weeks was well tolerated and produced significant, increasing improvement in hepatic fibrosis, durable suppression of HBV replication, normalization of liver enzymes, and delayed development of resistance.

  • long term therapy with Adefovir Dipivoxil for hbeag negative chronic hepatitis b
    The New England Journal of Medicine, 2005
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, S Arterburn, S Xiong
    Abstract:

    Background Treatment with Adefovir Dipivoxil for 48 weeks resulted in histologic, virologic, and biochemical improvement in patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy. Methods One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of Adefovir Dipivoxil or placebo once daily for 48 weeks (ratio, 2:1). After week 48, patients receiving Adefovir Dipivoxil were again randomly assigned either to receive an additional 48 weeks of the drug or to switch to placebo. Patients originally assigned to placebo were switched to Adefovir Dipivoxil. Patients treated with Adefovir Dipivoxil during weeks 49 through 96 were subsequently offered continued therapy. The primary end points were changes in hepatitis B virus (HBV) DNA and alanine aminotransferase levels. Results Treatment with Adefovir Dipivoxil resulted in a median decrease in serum HBV DNA of 3.47 log ...

  • Adefovir Dipivoxil for the treatment of hepatitis b e antigen positive chronic hepatitis b
    The New England Journal of Medicine, 2003
    Co-Authors: Patrick Marcellin, Tingtsung Chang, Zachary Goodman, S Xiong, Myron J Tong, William Sievert, Mitchell L Shiffman, Lennox J Jeffers, Michael Wulfsohn, Carol L Brosgart
    Abstract:

    Background In preclinical and phase 2 studies, Adefovir Dipivoxil demonstrated potent activity against hepatitis B virus (HBV), including lamivudine-resistant strains. Methods We randomly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) to receive 10 mg of Adefovir Dipivoxil (172 patients), 30 mg of Adefovir Dipivoxil (173), or placebo (170) daily for 48 weeks. The primary end point was histologic improvement in the 10-mg group as compared with the placebo group. Results After 48 weeks of treatment, significantly more patients who received 10 mg or 30 mg of Adefovir Dipivoxil per day than who received placebo had histologic improvement (53 percent [P<0.001], 59 percent [P<0.001], and 25 percent, respectively), a reduction in serum HBV DNA levels (by a median of 3.52 [P<0.001], 4.76 [P<0.001], and 0.55 log copies per milliliter, respectively), undetectable levels (fewer than 400 copies per milliliter) of serum HBV DNA (21 percent [P<0.001], 39 percent [P<0....

  • Adefovir Dipivoxil for the treatment of hepatitis b e antigen negative chronic hepatitis b
    The New England Journal of Medicine, 2003
    Co-Authors: Stephanos J Hadziyannis, Nicolaos C Tassopoulos, Jenny E Heathcote, Tingtsung Chang, G Kitis, Mario Rizzetto, Patrick Marcellin, Zachary Goodman, Michael Wulfsohn, S Xiong
    Abstract:

    Background Adefovir Dipivoxil, a nucleotide analogue, demonstrated clinically significant antiviral activity in patients with chronic hepatitis B in phase 1 and 2 clinical trials. Methods We randomly assigned 185 patients with chronic hepatitis B who were negative for hepatitis B e antigen (HBeAg) to receive either 10 mg of Adefovir Dipivoxil or placebo once daily for 48 weeks in a 2:1 ratio and a double-blind manner. The primary end point was histologic improvement. Results At week 48, 64 percent of patients who had base-line liver-biopsy specimens available in the Adefovir Dipivoxil group had improvement in histologic liver abnormalities (77 of 121), as compared with 33 percent of patients in the placebo group (19 of 57, P<0.001). Serum hepatitis B virus (HBV) DNA levels were reduced to fewer than 400 copies per milliliter in 51 percent of patients in the Adefovir Dipivoxil group (63 of 123) and in 0 percent of those in the placebo group (0 of 61, P<0.001). The median decrease in log-transformed HBV DNA...

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  • progress in the treatment of chronic hepatitis b long term experience with Adefovir Dipivoxil
    Journal of Antimicrobial Chemotherapy, 2007
    Co-Authors: William E Delaney
    Abstract:

    Most chronic hepatitis B patients do not undergo a curative response to interferon-a or nucleoside/ nucleotide-based regimens and require long-term therapy. Long-term safety, efficacy and resistance profiles of hepatitis B virus (HBV) drugs are therefore crucial issues for patient management. Adefovir Dipivoxil is a nucleotide prodrug indicated for the treatment of patients with hepatitis B e antigen positive or hepatitis B e antigen negative chronic hepatitis B, lamivudine-resistant HBV infection, HBV infection pre- or post-liver transplantation, or HlV co-infection. Long-term data from clinical trials of up to 5 years duration of Adefovir Dipivoxil have recently become available and are reviewed here. These data demonstrate that Adefovir Dipivoxil therapy results in sustained efficacy and safety in the majority of patients after multiple years of treatment. The efficacy of Adefovir Dipivoxil in treating lamivudineresistant HBV and the delayed emergence of Adefovir resistance are key factors contributing to the durable response achieved in broad groups of chronic hepatitis B patients.

  • activity of Adefovir Dipivoxil against all patterns of lamivudine resistant hepatitis b viruses in patients
    Journal of Viral Hepatitis, 2005
    Co-Authors: Chris Westland, Michael Wulfsohn, Carol L Brosgart, William E Delaney, Huiling Yang, Craig S Gibbs, Michael D Miller, Eugene R Schiff, Nicole Lama, Shelly Xiong
    Abstract:

    Summary.  One hundred and thirty-one post-liver transplantation patients with chronic hepatitis B and failing lamivudine therapy with detectable serum hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays or ≥1 × 106 copies/mL by polymerase chain reaction, and elevated alanine transaminase levels despite continuous lamivudine, were enrolled in an open-label study of Adefovir Dipivoxil. The B and C domains of HBV polymerase were sequenced for baseline samples to determine the presence of lamivudine resistance mutations. The results showed that 98% of the samples had tyrosine-methionine-aspartate-aspartate (YMDD) mutations, indicating a strong correlation between the above clinical definition of lamivudine treatment failure and the presence of YMDD mutations. In addition to the rtM204V/I and the rtL180M mutations, the mutation rtV173L was identified in 19% of patients. Four major patterns of lamivudine-resistant HBV were identified: rtL180M + rtM204V (60%), rtV173L + rtL180M + rtM204V (19%), rtM204I (9%) and rtL180M + rtM204I (9%). Treatment with Adefovir Dipivoxil showed similar antiviral efficacy in patients with lamivudine-resistant virus from all four patterns.

  • hepatitis b virus genotypes and virologic response in 694 patients in phase iii studies of Adefovir Dipivoxil
    Gastroenterology, 2003
    Co-Authors: Chris Westland, Stephanos J Hadziyannis, Patrick Marcellin, Carol L Brosgart, William E Delaney, Huiling Yang, Shanshan Chen, Robert G Gish, Craig S Gibbs, Michael D Miller
    Abstract:

    Abstract Background & aims: Hepatitis B virus (HBV) genotype may influence disease progression and antiviral response. We therefore analyzed the frequency and distribution of genotypes in patients from 2 multinational phase III studies of Adefovir Dipivoxil. Antiviral efficacy of Adefovir Dipivoxil 10-mg therapy was examined with respect to HBV genotype, hepatitis B e antigen (HBeAg) serostatus, and race. Methods: HBV genotypes were assigned by phylogenetic analyses of DNA sequences amplified from baseline serum samples (n = 694). Results: Patients from Asia/Oceania were infected predominantly with genotypes B and C, whereas patients from Western European countries were infected predominantly with genotypes A and D. In Mediterranean countries, genotype D was dominant. The most common genotype in North America was C, followed by A, B, and D. Regardless of location, Asian patients were infected predominantly with genotypes B or C, whereas Caucasian patients were infected predominantly with A or D. There were significant differences in the baseline serum HBV-DNA levels of patients infected with different HBV genotypes regardless of HBeAg serostatus. Forty-eight weeks of Adefovir Dipivoxil 10-mg therapy resulted in potent reductions in serum HBV DNA with no significant differences based on genotype, HBeAg status, or race; similarly, there was no statistical difference in HBeAg seroconversion rates between genotypes in these patients. Conclusions: HBV genotypes were distributed asymmetrically with respect to race, geography, and HBeAg status. Forty-eight weeks of Adefovir Dipivoxil therapy resulted in significant decreases in serum HBV-DNA levels in patients regardless of HBV genotype, HBeAg status, or race.