Adefovir Dipivoxil Therapy for Lamivudine-Resistant Hepatitis B in Pre- and Post-Liver Transplantation Patients

Eugene R Schiff, Ching Lung Lai, Stefanos Hadziyannis, Peter Neuhaus, Norah Terrault, Massimo Colombo, Hans L. Tillmann, Didier Samuel, Stefan Zeuzem, Leslie Lilly, Maria Rendina, Jean Pierre Villeneuve, Nicole Lama, Craig James, Michael S. Wulfsohn, Hamid Namini, Christopher Westland, Shelly Xiong, Gavin S. Choy, Sally Van DorenJohn Fry, Carol L. Brosgart

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Abstract

Three-+hundred and twenty-four patients were enrolled in an open-label, multicenter, international study in which pre- and post-liver transplantation (LT) patients with recurrent chronic hepatitis B (CHB) and evidence of lamivudine-resistant HBV were treated with adefovir dipivoxil 10 mg once daily. In the pre- and post-LT cohorts, 128 and 196 patients were treated for a median duration of 18.7 and 56.1 weeks, respectively. In patients who received 48 weeks of treatment, 81% of the pre-LT and 34% of the post-LT cohort achieved undetectable serum hepatitis B virus (HBV) DNA (Roche Amplicor Monitor™ polymerase chain reaction [PCR] assay lower limit of quantification [LLQ] < 400 copies/mL) with a median change in serum HBV DNA from baseline of -4.1 log10 and -4.3 log10 copies/mL, respectively. Serum alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 76%, 81%, 50%, and 83% of pre-LT patients and 49%, 76%, 75%, and 20% of post-LT patients. The Child-Pugh-Turcotte (CPT) score improved in over 90% of patients in both cohorts. Genotypic analysis of 122 HBV baseline samples revealed that 98% of these patients had lamivudine-resistant mutant HBV. No adefovir resistance mutations were identified in patients after 48 weeks of therapy. One-year survival was 84% for pre-LT and 93% for post-LT patients (Kaplan-Meier analysis). Treatment-related adverse effects associated with adefovir dipivoxil in this setting were primarily mild to moderate in severity. In conclusion, 48 weeks of adefovir dipivoxil resulted in significant improvements in virologic, biochemical, and clinical parameters in CHB patients pre- and post-LT with lamivudine-resistant HBV.

Original languageEnglish
Pages (from-to)1419-1427
Number of pages9
JournalHepatology
Volume38
Issue number6
DOIs
StatePublished - Dec 1 2003

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Lamivudine
Hepatitis B
Liver Transplantation
Hepatitis B virus
Therapeutics
Chronic Hepatitis B
adefovir dipivoxil
Serum
DNA
Prothrombin Time
Kaplan-Meier Estimate
Alanine Transaminase
Bilirubin
Multicenter Studies
Albumins

ASJC Scopus subject areas

  • Hepatology

Cite this

Schiff, E. R., Lai, C. L., Hadziyannis, S., Neuhaus, P., Terrault, N., Colombo, M., ... Brosgart, C. L. (2003). Adefovir Dipivoxil Therapy for Lamivudine-Resistant Hepatitis B in Pre- and Post-Liver Transplantation Patients. Hepatology, 38(6), 1419-1427. https://doi.org/10.1016/j.hep.2003.09.040

Adefovir Dipivoxil Therapy for Lamivudine-Resistant Hepatitis B in Pre- and Post-Liver Transplantation Patients. / Schiff, Eugene R; Lai, Ching Lung; Hadziyannis, Stefanos; Neuhaus, Peter; Terrault, Norah; Colombo, Massimo; Tillmann, Hans L.; Samuel, Didier; Zeuzem, Stefan; Lilly, Leslie; Rendina, Maria; Villeneuve, Jean Pierre; Lama, Nicole; James, Craig; Wulfsohn, Michael S.; Namini, Hamid; Westland, Christopher; Xiong, Shelly; Choy, Gavin S.; Van Doren, Sally; Fry, John; Brosgart, Carol L.

In: Hepatology, Vol. 38, No. 6, 01.12.2003, p. 1419-1427.

Research output: Contribution to journalArticle

Schiff, ER, Lai, CL, Hadziyannis, S, Neuhaus, P, Terrault, N, Colombo, M, Tillmann, HL, Samuel, D, Zeuzem, S, Lilly, L, Rendina, M, Villeneuve, JP, Lama, N, James, C, Wulfsohn, MS, Namini, H, Westland, C, Xiong, S, Choy, GS, Van Doren, S, Fry, J & Brosgart, CL 2003, 'Adefovir Dipivoxil Therapy for Lamivudine-Resistant Hepatitis B in Pre- and Post-Liver Transplantation Patients', Hepatology, vol. 38, no. 6, pp. 1419-1427. https://doi.org/10.1016/j.hep.2003.09.040
Schiff, Eugene R ; Lai, Ching Lung ; Hadziyannis, Stefanos ; Neuhaus, Peter ; Terrault, Norah ; Colombo, Massimo ; Tillmann, Hans L. ; Samuel, Didier ; Zeuzem, Stefan ; Lilly, Leslie ; Rendina, Maria ; Villeneuve, Jean Pierre ; Lama, Nicole ; James, Craig ; Wulfsohn, Michael S. ; Namini, Hamid ; Westland, Christopher ; Xiong, Shelly ; Choy, Gavin S. ; Van Doren, Sally ; Fry, John ; Brosgart, Carol L. / Adefovir Dipivoxil Therapy for Lamivudine-Resistant Hepatitis B in Pre- and Post-Liver Transplantation Patients. In: Hepatology. 2003 ; Vol. 38, No. 6. pp. 1419-1427.
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abstract = "Three-+hundred and twenty-four patients were enrolled in an open-label, multicenter, international study in which pre- and post-liver transplantation (LT) patients with recurrent chronic hepatitis B (CHB) and evidence of lamivudine-resistant HBV were treated with adefovir dipivoxil 10 mg once daily. In the pre- and post-LT cohorts, 128 and 196 patients were treated for a median duration of 18.7 and 56.1 weeks, respectively. In patients who received 48 weeks of treatment, 81{\%} of the pre-LT and 34{\%} of the post-LT cohort achieved undetectable serum hepatitis B virus (HBV) DNA (Roche Amplicor Monitor™ polymerase chain reaction [PCR] assay lower limit of quantification [LLQ] < 400 copies/mL) with a median change in serum HBV DNA from baseline of -4.1 log10 and -4.3 log10 copies/mL, respectively. Serum alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 76{\%}, 81{\%}, 50{\%}, and 83{\%} of pre-LT patients and 49{\%}, 76{\%}, 75{\%}, and 20{\%} of post-LT patients. The Child-Pugh-Turcotte (CPT) score improved in over 90{\%} of patients in both cohorts. Genotypic analysis of 122 HBV baseline samples revealed that 98{\%} of these patients had lamivudine-resistant mutant HBV. No adefovir resistance mutations were identified in patients after 48 weeks of therapy. One-year survival was 84{\%} for pre-LT and 93{\%} for post-LT patients (Kaplan-Meier analysis). Treatment-related adverse effects associated with adefovir dipivoxil in this setting were primarily mild to moderate in severity. In conclusion, 48 weeks of adefovir dipivoxil resulted in significant improvements in virologic, biochemical, and clinical parameters in CHB patients pre- and post-LT with lamivudine-resistant HBV.",
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AU - Neuhaus, Peter

AU - Terrault, Norah

AU - Colombo, Massimo

AU - Tillmann, Hans L.

AU - Samuel, Didier

AU - Zeuzem, Stefan

AU - Lilly, Leslie

AU - Rendina, Maria

AU - Villeneuve, Jean Pierre

AU - Lama, Nicole

AU - James, Craig

AU - Wulfsohn, Michael S.

AU - Namini, Hamid

AU - Westland, Christopher

AU - Xiong, Shelly

AU - Choy, Gavin S.

AU - Van Doren, Sally

AU - Fry, John

AU - Brosgart, Carol L.

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N2 - Three-+hundred and twenty-four patients were enrolled in an open-label, multicenter, international study in which pre- and post-liver transplantation (LT) patients with recurrent chronic hepatitis B (CHB) and evidence of lamivudine-resistant HBV were treated with adefovir dipivoxil 10 mg once daily. In the pre- and post-LT cohorts, 128 and 196 patients were treated for a median duration of 18.7 and 56.1 weeks, respectively. In patients who received 48 weeks of treatment, 81% of the pre-LT and 34% of the post-LT cohort achieved undetectable serum hepatitis B virus (HBV) DNA (Roche Amplicor Monitor™ polymerase chain reaction [PCR] assay lower limit of quantification [LLQ] < 400 copies/mL) with a median change in serum HBV DNA from baseline of -4.1 log10 and -4.3 log10 copies/mL, respectively. Serum alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 76%, 81%, 50%, and 83% of pre-LT patients and 49%, 76%, 75%, and 20% of post-LT patients. The Child-Pugh-Turcotte (CPT) score improved in over 90% of patients in both cohorts. Genotypic analysis of 122 HBV baseline samples revealed that 98% of these patients had lamivudine-resistant mutant HBV. No adefovir resistance mutations were identified in patients after 48 weeks of therapy. One-year survival was 84% for pre-LT and 93% for post-LT patients (Kaplan-Meier analysis). Treatment-related adverse effects associated with adefovir dipivoxil in this setting were primarily mild to moderate in severity. In conclusion, 48 weeks of adefovir dipivoxil resulted in significant improvements in virologic, biochemical, and clinical parameters in CHB patients pre- and post-LT with lamivudine-resistant HBV.

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