Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B

Antiviral responses and evolution of mutations

Hyung Joon Yim, Hyun Jung Lee, Sang Jun Suh, Yeon Seok Seo, Chang Wook Kim, Chang Don Lee, Sang Hoon Park, Myung Seok Lee, Choong Kee Park, Hee Bok Chae, Moonyoung Kim, Soonkoo Baik, Yun Soo Kim, Ju Hyun Kim, Jung Il Lee, Jin Woo Lee, Sun Pyo Hong, Soon Ho Um

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. Methods: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. Results: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). Conclusions: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

Original languageEnglish
Pages (from-to)239-247
Number of pages9
JournalIntervirology
Volume57
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

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Chronic Hepatitis B
Antiviral Agents
Hepatitis B virus
Mutation
Lamivudine
DNA
Therapeutics
Serum
lamivudine-adefovir combination
entecavir
Virus Diseases

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

Yim, Hyung Joon ; Lee, Hyun Jung ; Suh, Sang Jun ; Seo, Yeon Seok ; Kim, Chang Wook ; Lee, Chang Don ; Park, Sang Hoon ; Lee, Myung Seok ; Park, Choong Kee ; Chae, Hee Bok ; Kim, Moonyoung ; Baik, Soonkoo ; Kim, Yun Soo ; Kim, Ju Hyun ; Lee, Jung Il ; Lee, Jin Woo ; Hong, Sun Pyo ; Um, Soon Ho. / Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B : Antiviral responses and evolution of mutations. In: Intervirology. 2014 ; Vol. 57, No. 5. pp. 239-247.
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title = "Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B: Antiviral responses and evolution of mutations",
abstract = "Objective: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. Methods: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. Results: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50{\%}), rtS202G (25{\%}) and mixed ETV-resistant mutations (25{\%}) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5{\%}). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7{\%}). Conclusions: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.",
author = "Yim, {Hyung Joon} and Lee, {Hyun Jung} and Suh, {Sang Jun} and Seo, {Yeon Seok} and Kim, {Chang Wook} and Lee, {Chang Don} and Park, {Sang Hoon} and Lee, {Myung Seok} and Park, {Choong Kee} and Chae, {Hee Bok} and Moonyoung Kim and Soonkoo Baik and Kim, {Yun Soo} and Kim, {Ju Hyun} and Lee, {Jung Il} and Lee, {Jin Woo} and Hong, {Sun Pyo} and Um, {Soon Ho}",
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Yim, HJ, Lee, HJ, Suh, SJ, Seo, YS, Kim, CW, Lee, CD, Park, SH, Lee, MS, Park, CK, Chae, HB, Kim, M, Baik, S, Kim, YS, Kim, JH, Lee, JI, Lee, JW, Hong, SP & Um, SH 2014, 'Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B: Antiviral responses and evolution of mutations', Intervirology, vol. 57, no. 5, pp. 239-247. https://doi.org/10.1159/000360399

Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B : Antiviral responses and evolution of mutations. / Yim, Hyung Joon; Lee, Hyun Jung; Suh, Sang Jun; Seo, Yeon Seok; Kim, Chang Wook; Lee, Chang Don; Park, Sang Hoon; Lee, Myung Seok; Park, Choong Kee; Chae, Hee Bok; Kim, Moonyoung; Baik, Soonkoo; Kim, Yun Soo; Kim, Ju Hyun; Lee, Jung Il; Lee, Jin Woo; Hong, Sun Pyo; Um, Soon Ho.

In: Intervirology, Vol. 57, No. 5, 01.01.2014, p. 239-247.

Research output: Contribution to journalArticle

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T1 - Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B

T2 - Antiviral responses and evolution of mutations

AU - Yim, Hyung Joon

AU - Lee, Hyun Jung

AU - Suh, Sang Jun

AU - Seo, Yeon Seok

AU - Kim, Chang Wook

AU - Lee, Chang Don

AU - Park, Sang Hoon

AU - Lee, Myung Seok

AU - Park, Choong Kee

AU - Chae, Hee Bok

AU - Kim, Moonyoung

AU - Baik, Soonkoo

AU - Kim, Yun Soo

AU - Kim, Ju Hyun

AU - Lee, Jung Il

AU - Lee, Jin Woo

AU - Hong, Sun Pyo

AU - Um, Soon Ho

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objective: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. Methods: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. Results: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). Conclusions: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

AB - Objective: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. Methods: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. Results: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). Conclusions: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

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