Entecavir plus tenofovir combination therapy in patients with multidrug-resistant chronic hepatitis B: results of a multicentre, prospective study

Junyong Park, Chang Wook Kim, Si Hyun Bae, Kyu Sik Jung, Hee Yeon Kim, Seung Kew Yoon, KwangHyub Han, SangHoon Ahn

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16 Citations (Scopus)

Abstract

Background & Aims: Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in multidrug-resistant (MDR) CHB patients. Methods: In this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks. Results: A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2–6) were included. At baseline, median age was 47.0 years, 89.1% were HBeAg(+), and median HBV DNA was 4.24 (range, 2.11–6.73) log 10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 55/64 (85.9%) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log 10 IU/ml and 2.38 log 10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients. Conclusions: In difficult-to-treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.

Original languageEnglish
Pages (from-to)1108-1115
Number of pages8
JournalLiver International
Volume36
Issue number8
DOIs
Publication statusPublished - 2016 Aug 1

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Tenofovir
Chronic Hepatitis B
Multicenter Studies
Prospective Studies
Antiviral Agents
DNA
Therapeutics
Mutation
Hepatitis B e Antigens
entecavir
Multiple Drug Resistance
Nucleosides

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

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title = "Entecavir plus tenofovir combination therapy in patients with multidrug-resistant chronic hepatitis B: results of a multicentre, prospective study",
abstract = "Background & Aims: Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in multidrug-resistant (MDR) CHB patients. Methods: In this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks. Results: A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2–6) were included. At baseline, median age was 47.0 years, 89.1{\%} were HBeAg(+), and median HBV DNA was 4.24 (range, 2.11–6.73) log 10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4{\%}), 36/64 (56.3{\%}), 43/64 (67.2{\%}) and 55/64 (85.9{\%}) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log 10 IU/ml and 2.38 log 10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients. Conclusions: In difficult-to-treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.",
author = "Junyong Park and Kim, {Chang Wook} and Bae, {Si Hyun} and Jung, {Kyu Sik} and Kim, {Hee Yeon} and Yoon, {Seung Kew} and KwangHyub Han and SangHoon Ahn",
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Entecavir plus tenofovir combination therapy in patients with multidrug-resistant chronic hepatitis B : results of a multicentre, prospective study. / Park, Junyong; Kim, Chang Wook; Bae, Si Hyun; Jung, Kyu Sik; Kim, Hee Yeon; Yoon, Seung Kew; Han, KwangHyub; Ahn, SangHoon.

In: Liver International, Vol. 36, No. 8, 01.08.2016, p. 1108-1115.

Research output: Contribution to journalArticle

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T1 - Entecavir plus tenofovir combination therapy in patients with multidrug-resistant chronic hepatitis B

T2 - results of a multicentre, prospective study

AU - Park, Junyong

AU - Kim, Chang Wook

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AU - Kim, Hee Yeon

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AU - Han, KwangHyub

AU - Ahn, SangHoon

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N2 - Background & Aims: Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in multidrug-resistant (MDR) CHB patients. Methods: In this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks. Results: A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2–6) were included. At baseline, median age was 47.0 years, 89.1% were HBeAg(+), and median HBV DNA was 4.24 (range, 2.11–6.73) log 10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 55/64 (85.9%) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log 10 IU/ml and 2.38 log 10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients. Conclusions: In difficult-to-treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.

AB - Background & Aims: Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in multidrug-resistant (MDR) CHB patients. Methods: In this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks. Results: A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2–6) were included. At baseline, median age was 47.0 years, 89.1% were HBeAg(+), and median HBV DNA was 4.24 (range, 2.11–6.73) log 10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 55/64 (85.9%) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log 10 IU/ml and 2.38 log 10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients. Conclusions: In difficult-to-treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.

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