Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic hepatitis B in hepatitis B e antigen-positive patients with liver cirrhosis

Won Hyeok Choe, So Young Kwon, Byung Kook Kim, Soon Young Ko, Jong Eun Yeon, Kwan Soo Byun, Gyun Hwan Kim, Chang Hong Lee

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background/Aims: There is no consensus on the management of patients with adefovir (ADV)-resistant hepatitis B virus (HBV) infection. The aim of this study was to investigate whether tenofovir disoproxil fumarate (TDF) combined with lamivudine (LMV) is effective and safe in patients with resistance to or non-response to ADV. Methods: Six patients with HBV-related cirrhosis, viral breakthrough during LMV therapy and viral breakthrough or non-response during ADV therapy were treated daily with TDF plus LMV for at least 6 months. The HBV DNA level, alanine aminotransferase (ALT), the Child-Pugh score and serum creatinine were monitored. Genotypic LMV- or ADV-resistant mutations were measured in stored samples. Results: In five of six patients, ADV-resistant mutations at rt181 or rt236 were detected during ADV therapy. At 6 months of starting TDF/LMV combination, HBV DNA levels became undetectable (detection limit, 400 copies/ml) in four of six patients. Within 12 months, HBV DNA levels became undetectable in all patients, and ALT levels were normalized in four of six patients. These responses persisted up to the end of the observation period (median duration 16.5 months, range 6-21 months). The Child-Pugh scores improved in two of three patients with hepatic decompensation. No significant changes in serum creatinine were observed. Conclusion: Our data demonstrated that TDF plus LMV safely and markedly suppressed HBV replication in patients with resistance to or non-response to ADV. This study suggests that this combination may be a promising rescue therapy for these patients, particularly those with liver cirrhosis or pre-existing LMV resistance.

Original languageEnglish
Pages (from-to)814-820
Number of pages7
JournalLiver International
Volume28
Issue number6
DOIs
Publication statusPublished - 2008 Jul 1

Fingerprint

Tenofovir
Lamivudine
Hepatitis B e Antigens
Chronic Hepatitis B
Liver Cirrhosis
Hepatitis B virus
Therapeutics
Alanine Transaminase
DNA
Creatinine
adefovir
Mutation

Keywords

  • Adefovir dipivoxil
  • Antiviral drug resistance
  • Chronic hepatitis B
  • Lamivudine
  • Liver cirrhosis
  • Tenofovir disoproxil fumarate

ASJC Scopus subject areas

  • Hepatology

Cite this

Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic hepatitis B in hepatitis B e antigen-positive patients with liver cirrhosis. / Choe, Won Hyeok; Kwon, So Young; Kim, Byung Kook; Ko, Soon Young; Yeon, Jong Eun; Byun, Kwan Soo; Kim, Gyun Hwan; Lee, Chang Hong.

In: Liver International, Vol. 28, No. 6, 01.07.2008, p. 814-820.

Research output: Contribution to journalArticle

Choe, Won Hyeok ; Kwon, So Young ; Kim, Byung Kook ; Ko, Soon Young ; Yeon, Jong Eun ; Byun, Kwan Soo ; Kim, Gyun Hwan ; Lee, Chang Hong. / Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic hepatitis B in hepatitis B e antigen-positive patients with liver cirrhosis. In: Liver International. 2008 ; Vol. 28, No. 6. pp. 814-820.
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abstract = "Background/Aims: There is no consensus on the management of patients with adefovir (ADV)-resistant hepatitis B virus (HBV) infection. The aim of this study was to investigate whether tenofovir disoproxil fumarate (TDF) combined with lamivudine (LMV) is effective and safe in patients with resistance to or non-response to ADV. Methods: Six patients with HBV-related cirrhosis, viral breakthrough during LMV therapy and viral breakthrough or non-response during ADV therapy were treated daily with TDF plus LMV for at least 6 months. The HBV DNA level, alanine aminotransferase (ALT), the Child-Pugh score and serum creatinine were monitored. Genotypic LMV- or ADV-resistant mutations were measured in stored samples. Results: In five of six patients, ADV-resistant mutations at rt181 or rt236 were detected during ADV therapy. At 6 months of starting TDF/LMV combination, HBV DNA levels became undetectable (detection limit, 400 copies/ml) in four of six patients. Within 12 months, HBV DNA levels became undetectable in all patients, and ALT levels were normalized in four of six patients. These responses persisted up to the end of the observation period (median duration 16.5 months, range 6-21 months). The Child-Pugh scores improved in two of three patients with hepatic decompensation. No significant changes in serum creatinine were observed. Conclusion: Our data demonstrated that TDF plus LMV safely and markedly suppressed HBV replication in patients with resistance to or non-response to ADV. This study suggests that this combination may be a promising rescue therapy for these patients, particularly those with liver cirrhosis or pre-existing LMV resistance.",
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T1 - Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic hepatitis B in hepatitis B e antigen-positive patients with liver cirrhosis

AU - Choe, Won Hyeok

AU - Kwon, So Young

AU - Kim, Byung Kook

AU - Ko, Soon Young

AU - Yeon, Jong Eun

AU - Byun, Kwan Soo

AU - Kim, Gyun Hwan

AU - Lee, Chang Hong

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N2 - Background/Aims: There is no consensus on the management of patients with adefovir (ADV)-resistant hepatitis B virus (HBV) infection. The aim of this study was to investigate whether tenofovir disoproxil fumarate (TDF) combined with lamivudine (LMV) is effective and safe in patients with resistance to or non-response to ADV. Methods: Six patients with HBV-related cirrhosis, viral breakthrough during LMV therapy and viral breakthrough or non-response during ADV therapy were treated daily with TDF plus LMV for at least 6 months. The HBV DNA level, alanine aminotransferase (ALT), the Child-Pugh score and serum creatinine were monitored. Genotypic LMV- or ADV-resistant mutations were measured in stored samples. Results: In five of six patients, ADV-resistant mutations at rt181 or rt236 were detected during ADV therapy. At 6 months of starting TDF/LMV combination, HBV DNA levels became undetectable (detection limit, 400 copies/ml) in four of six patients. Within 12 months, HBV DNA levels became undetectable in all patients, and ALT levels were normalized in four of six patients. These responses persisted up to the end of the observation period (median duration 16.5 months, range 6-21 months). The Child-Pugh scores improved in two of three patients with hepatic decompensation. No significant changes in serum creatinine were observed. Conclusion: Our data demonstrated that TDF plus LMV safely and markedly suppressed HBV replication in patients with resistance to or non-response to ADV. This study suggests that this combination may be a promising rescue therapy for these patients, particularly those with liver cirrhosis or pre-existing LMV resistance.

AB - Background/Aims: There is no consensus on the management of patients with adefovir (ADV)-resistant hepatitis B virus (HBV) infection. The aim of this study was to investigate whether tenofovir disoproxil fumarate (TDF) combined with lamivudine (LMV) is effective and safe in patients with resistance to or non-response to ADV. Methods: Six patients with HBV-related cirrhosis, viral breakthrough during LMV therapy and viral breakthrough or non-response during ADV therapy were treated daily with TDF plus LMV for at least 6 months. The HBV DNA level, alanine aminotransferase (ALT), the Child-Pugh score and serum creatinine were monitored. Genotypic LMV- or ADV-resistant mutations were measured in stored samples. Results: In five of six patients, ADV-resistant mutations at rt181 or rt236 were detected during ADV therapy. At 6 months of starting TDF/LMV combination, HBV DNA levels became undetectable (detection limit, 400 copies/ml) in four of six patients. Within 12 months, HBV DNA levels became undetectable in all patients, and ALT levels were normalized in four of six patients. These responses persisted up to the end of the observation period (median duration 16.5 months, range 6-21 months). The Child-Pugh scores improved in two of three patients with hepatic decompensation. No significant changes in serum creatinine were observed. Conclusion: Our data demonstrated that TDF plus LMV safely and markedly suppressed HBV replication in patients with resistance to or non-response to ADV. This study suggests that this combination may be a promising rescue therapy for these patients, particularly those with liver cirrhosis or pre-existing LMV resistance.

KW - Adefovir dipivoxil

KW - Antiviral drug resistance

KW - Chronic hepatitis B

KW - Lamivudine

KW - Liver cirrhosis

KW - Tenofovir disoproxil fumarate

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