Cargando…

Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients

BACKGROUND: The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear. METH...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Heon Ju, Kim, Sang Jin, Kweon, Young Oh, Park, Soo Young, Heo, Jeong, Woo, Hyun Young, Hwang, Jae Seok, Chung, Woo Jin, Lee, Chang Hyeong, Kim, Byung Seok, Suh, Jeong Ill, Tak, Won Young, Jang, Byoung Kuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766122/
https://www.ncbi.nlm.nih.gov/pubmed/29329305
http://dx.doi.org/10.1371/journal.pone.0190581
_version_ 1783292317966270464
author Lee, Heon Ju
Kim, Sang Jin
Kweon, Young Oh
Park, Soo Young
Heo, Jeong
Woo, Hyun Young
Hwang, Jae Seok
Chung, Woo Jin
Lee, Chang Hyeong
Kim, Byung Seok
Suh, Jeong Ill
Tak, Won Young
Jang, Byoung Kuk
author_facet Lee, Heon Ju
Kim, Sang Jin
Kweon, Young Oh
Park, Soo Young
Heo, Jeong
Woo, Hyun Young
Hwang, Jae Seok
Chung, Woo Jin
Lee, Chang Hyeong
Kim, Byung Seok
Suh, Jeong Ill
Tak, Won Young
Jang, Byoung Kuk
author_sort Lee, Heon Ju
collection PubMed
description BACKGROUND: The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear. METHODS: In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96. RESULTS: Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84–5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m(2), p = 0.000) CONCLUSIONS: Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function. TRIAL REGISTRATION: ClinicalTrials.gov NCT01732367
format Online
Article
Text
id pubmed-5766122
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-57661222018-01-23 Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients Lee, Heon Ju Kim, Sang Jin Kweon, Young Oh Park, Soo Young Heo, Jeong Woo, Hyun Young Hwang, Jae Seok Chung, Woo Jin Lee, Chang Hyeong Kim, Byung Seok Suh, Jeong Ill Tak, Won Young Jang, Byoung Kuk PLoS One Research Article BACKGROUND: The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear. METHODS: In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96. RESULTS: Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84–5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m(2), p = 0.000) CONCLUSIONS: Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function. TRIAL REGISTRATION: ClinicalTrials.gov NCT01732367 Public Library of Science 2018-01-12 /pmc/articles/PMC5766122/ /pubmed/29329305 http://dx.doi.org/10.1371/journal.pone.0190581 Text en © 2018 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Heon Ju
Kim, Sang Jin
Kweon, Young Oh
Park, Soo Young
Heo, Jeong
Woo, Hyun Young
Hwang, Jae Seok
Chung, Woo Jin
Lee, Chang Hyeong
Kim, Byung Seok
Suh, Jeong Ill
Tak, Won Young
Jang, Byoung Kuk
Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients
title Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients
title_full Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients
title_fullStr Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients
title_full_unstemmed Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients
title_short Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients
title_sort evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis b patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766122/
https://www.ncbi.nlm.nih.gov/pubmed/29329305
http://dx.doi.org/10.1371/journal.pone.0190581
work_keys_str_mv AT leeheonju evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT kimsangjin evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT kweonyoungoh evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT parksooyoung evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT heojeong evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT woohyunyoung evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT hwangjaeseok evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT chungwoojin evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT leechanghyeong evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT kimbyungseok evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT suhjeongill evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT takwonyoung evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients
AT jangbyoungkuk evaluatingtheefficacyofswitchingfromlamivudineplusadefovirtotenofovirdisoproxilfumaratemonotherapyinlamivudineresistantstablehepatitisbpatients