Adefovir Dipivoxil Added to Ongoing Lamivudine in Chronic Hepatitis B with YMDD Mutant Hepatitis B Virus

Robert Perrillo, Hie Won Hann, David Mutimer, Bernard Willems, Nancy Leung, William M. Lee, Alison Moorat, Stephen Gardner, Mary Woessner, Eric Bourne, Carol L. Brosgart, Eugene R Schiff

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Abstract

Background & Aims: Prolonged lamivudine therapy is associated with treatment-resistant YMDD mutant hepatitis B virus (HBV). We evaluated the efficacy and safety of adding adefovir dipivoxil to lamivudine in 135 patients with chronic hepatitis B (CHB) and YMDD mutant HBV. Methods: Ninety-five patients with compensated CHB (group A) were randomized to adefovir 10 mg daily (n = 46) or placebo (n = 49) for 52 weeks while continuing treatment with lamivudine. Forty patients with decompensated hepatitis B or post-liver transplantation (group B) received adefovir and lamivudine. The primary end point was a decline in serum HBV DNA level to 105 copies/mL or a >2 log10 reduction from baseline at weeks 48 and 52. Results: HBV DNA response occurred in 85% of patients (39 of 46) in group A given combined therapy versus 11% (5 of 46) receiving lamivudine alone (P < 0.001), with a significant change in HBV DNA level from baseline (P < 0.001) between treatment groups (median, -4.6 vs. +0.3 log10 copies/mL, respectively). Normalization of alanine aminotransferase levels occurred in 31% of patients (14 of 45) receiving combined therapy versus 6% (3 of 48) receiving lamivudine alone (P = 0.002). Ninety-two percent of patients (36 of 39) in group B had an HBV DNA response (median change of -4.6 log10 copies/mL) and improved liver chemistries (P ≤ 5 0.001). Both treatment regimens were well tolerated, and renal function abnormalities were not observed in either group. Conclusions: The addition of adefovir dipivoxil to lamivudine in patients with CHB with compensated or decompensated liver disease due to YMDD mutant HBV is associated with virologic and biochemical improvement during 52 weeks of treatment and is well tolerated.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalGastroenterology
Volume126
Issue number1 SUPPL. 1
DOIs
StatePublished - Jan 1 2004

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Lamivudine
Chronic Hepatitis B
Hepatitis B virus
DNA
Therapeutics
adefovir dipivoxil
Hepatitis B
Alanine Transaminase
Liver Transplantation
Liver Diseases
Placebos
Kidney
Safety
Liver
Serum

ASJC Scopus subject areas

  • Gastroenterology

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Adefovir Dipivoxil Added to Ongoing Lamivudine in Chronic Hepatitis B with YMDD Mutant Hepatitis B Virus. / Perrillo, Robert; Hann, Hie Won; Mutimer, David; Willems, Bernard; Leung, Nancy; Lee, William M.; Moorat, Alison; Gardner, Stephen; Woessner, Mary; Bourne, Eric; Brosgart, Carol L.; Schiff, Eugene R.

In: Gastroenterology, Vol. 126, No. 1 SUPPL. 1, 01.01.2004, p. 81-90.

Research output: Contribution to journalArticle

Perrillo, R, Hann, HW, Mutimer, D, Willems, B, Leung, N, Lee, WM, Moorat, A, Gardner, S, Woessner, M, Bourne, E, Brosgart, CL & Schiff, ER 2004, 'Adefovir Dipivoxil Added to Ongoing Lamivudine in Chronic Hepatitis B with YMDD Mutant Hepatitis B Virus', Gastroenterology, vol. 126, no. 1 SUPPL. 1, pp. 81-90. https://doi.org/10.1053/j.gastro.2003.10.050
Perrillo, Robert ; Hann, Hie Won ; Mutimer, David ; Willems, Bernard ; Leung, Nancy ; Lee, William M. ; Moorat, Alison ; Gardner, Stephen ; Woessner, Mary ; Bourne, Eric ; Brosgart, Carol L. ; Schiff, Eugene R. / Adefovir Dipivoxil Added to Ongoing Lamivudine in Chronic Hepatitis B with YMDD Mutant Hepatitis B Virus. In: Gastroenterology. 2004 ; Vol. 126, No. 1 SUPPL. 1. pp. 81-90.
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abstract = "Background & Aims: Prolonged lamivudine therapy is associated with treatment-resistant YMDD mutant hepatitis B virus (HBV). We evaluated the efficacy and safety of adding adefovir dipivoxil to lamivudine in 135 patients with chronic hepatitis B (CHB) and YMDD mutant HBV. Methods: Ninety-five patients with compensated CHB (group A) were randomized to adefovir 10 mg daily (n = 46) or placebo (n = 49) for 52 weeks while continuing treatment with lamivudine. Forty patients with decompensated hepatitis B or post-liver transplantation (group B) received adefovir and lamivudine. The primary end point was a decline in serum HBV DNA level to 105 copies/mL or a >2 log10 reduction from baseline at weeks 48 and 52. Results: HBV DNA response occurred in 85{\%} of patients (39 of 46) in group A given combined therapy versus 11{\%} (5 of 46) receiving lamivudine alone (P < 0.001), with a significant change in HBV DNA level from baseline (P < 0.001) between treatment groups (median, -4.6 vs. +0.3 log10 copies/mL, respectively). Normalization of alanine aminotransferase levels occurred in 31{\%} of patients (14 of 45) receiving combined therapy versus 6{\%} (3 of 48) receiving lamivudine alone (P = 0.002). Ninety-two percent of patients (36 of 39) in group B had an HBV DNA response (median change of -4.6 log10 copies/mL) and improved liver chemistries (P ≤ 5 0.001). Both treatment regimens were well tolerated, and renal function abnormalities were not observed in either group. Conclusions: The addition of adefovir dipivoxil to lamivudine in patients with CHB with compensated or decompensated liver disease due to YMDD mutant HBV is associated with virologic and biochemical improvement during 52 weeks of treatment and is well tolerated.",
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T1 - Adefovir Dipivoxil Added to Ongoing Lamivudine in Chronic Hepatitis B with YMDD Mutant Hepatitis B Virus

AU - Perrillo, Robert

AU - Hann, Hie Won

AU - Mutimer, David

AU - Willems, Bernard

AU - Leung, Nancy

AU - Lee, William M.

AU - Moorat, Alison

AU - Gardner, Stephen

AU - Woessner, Mary

AU - Bourne, Eric

AU - Brosgart, Carol L.

AU - Schiff, Eugene R

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N2 - Background & Aims: Prolonged lamivudine therapy is associated with treatment-resistant YMDD mutant hepatitis B virus (HBV). We evaluated the efficacy and safety of adding adefovir dipivoxil to lamivudine in 135 patients with chronic hepatitis B (CHB) and YMDD mutant HBV. Methods: Ninety-five patients with compensated CHB (group A) were randomized to adefovir 10 mg daily (n = 46) or placebo (n = 49) for 52 weeks while continuing treatment with lamivudine. Forty patients with decompensated hepatitis B or post-liver transplantation (group B) received adefovir and lamivudine. The primary end point was a decline in serum HBV DNA level to 105 copies/mL or a >2 log10 reduction from baseline at weeks 48 and 52. Results: HBV DNA response occurred in 85% of patients (39 of 46) in group A given combined therapy versus 11% (5 of 46) receiving lamivudine alone (P < 0.001), with a significant change in HBV DNA level from baseline (P < 0.001) between treatment groups (median, -4.6 vs. +0.3 log10 copies/mL, respectively). Normalization of alanine aminotransferase levels occurred in 31% of patients (14 of 45) receiving combined therapy versus 6% (3 of 48) receiving lamivudine alone (P = 0.002). Ninety-two percent of patients (36 of 39) in group B had an HBV DNA response (median change of -4.6 log10 copies/mL) and improved liver chemistries (P ≤ 5 0.001). Both treatment regimens were well tolerated, and renal function abnormalities were not observed in either group. Conclusions: The addition of adefovir dipivoxil to lamivudine in patients with CHB with compensated or decompensated liver disease due to YMDD mutant HBV is associated with virologic and biochemical improvement during 52 weeks of treatment and is well tolerated.

AB - Background & Aims: Prolonged lamivudine therapy is associated with treatment-resistant YMDD mutant hepatitis B virus (HBV). We evaluated the efficacy and safety of adding adefovir dipivoxil to lamivudine in 135 patients with chronic hepatitis B (CHB) and YMDD mutant HBV. Methods: Ninety-five patients with compensated CHB (group A) were randomized to adefovir 10 mg daily (n = 46) or placebo (n = 49) for 52 weeks while continuing treatment with lamivudine. Forty patients with decompensated hepatitis B or post-liver transplantation (group B) received adefovir and lamivudine. The primary end point was a decline in serum HBV DNA level to 105 copies/mL or a >2 log10 reduction from baseline at weeks 48 and 52. Results: HBV DNA response occurred in 85% of patients (39 of 46) in group A given combined therapy versus 11% (5 of 46) receiving lamivudine alone (P < 0.001), with a significant change in HBV DNA level from baseline (P < 0.001) between treatment groups (median, -4.6 vs. +0.3 log10 copies/mL, respectively). Normalization of alanine aminotransferase levels occurred in 31% of patients (14 of 45) receiving combined therapy versus 6% (3 of 48) receiving lamivudine alone (P = 0.002). Ninety-two percent of patients (36 of 39) in group B had an HBV DNA response (median change of -4.6 log10 copies/mL) and improved liver chemistries (P ≤ 5 0.001). Both treatment regimens were well tolerated, and renal function abnormalities were not observed in either group. Conclusions: The addition of adefovir dipivoxil to lamivudine in patients with CHB with compensated or decompensated liver disease due to YMDD mutant HBV is associated with virologic and biochemical improvement during 52 weeks of treatment and is well tolerated.

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