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Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study
BACKGROUND & AIMS: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. METHODS: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC tr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362794/ https://www.ncbi.nlm.nih.gov/pubmed/37484211 http://dx.doi.org/10.1016/j.jhepr.2023.100790 |
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author | Sonneveld, Milan J. Chiu, Shao-Ming Park, Jun Yong Brakenhoff, Sylvia M. Kaewdech, Apichat Seto, Wai-Kay Tanaka, Yasuhito Carey, Ivana Papatheodoridi, Margarita Colombatto, Piero van Bömmel, Florian Berg, Thomas Zoulim, Fabien Ahn, Sang Hoon Dalekos, George N. Erler, Nicole S. Brunetto, Maurizia Wedemeyer, Heiner Cornberg, Markus Yuen, Man-Fung Agarwal, Kosh Boonstra, Andre Buti, Maria Piratvisuth, Teerha Papatheodoridis, George Chen, Chien-Hung Maasoumy, Benjamin |
author_facet | Sonneveld, Milan J. Chiu, Shao-Ming Park, Jun Yong Brakenhoff, Sylvia M. Kaewdech, Apichat Seto, Wai-Kay Tanaka, Yasuhito Carey, Ivana Papatheodoridi, Margarita Colombatto, Piero van Bömmel, Florian Berg, Thomas Zoulim, Fabien Ahn, Sang Hoon Dalekos, George N. Erler, Nicole S. Brunetto, Maurizia Wedemeyer, Heiner Cornberg, Markus Yuen, Man-Fung Agarwal, Kosh Boonstra, Andre Buti, Maria Piratvisuth, Teerha Papatheodoridis, George Chen, Chien-Hung Maasoumy, Benjamin |
author_sort | Sonneveld, Milan J. |
collection | PubMed |
description | BACKGROUND & AIMS: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. METHODS: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA >2,000 IU/ml + alanine aminotransferase >2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal. RESULTS: We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (<20,000 IU/ml) in 150 (20%) and high (>20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels <20,000 IU/ml vs. 60% among patients with pretreatment HBV DNA levels >20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p <0.001). In multivariable analysis, pretreatment HBV DNA levels <20,000 IU/ml were independently associated with a reduced likelihood of clinical relapse (adjusted hazard ratio 0.379, p <0.001) and with an increased chance of HBsAg loss (adjusted hazard ratio 2.872, p <0.001). CONCLUSIONS: Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of end-of-treatment viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations. IMPACT AND IMPLICATIONS: A subgroup of patients with chronic hepatitis B may not require retreatment after stopping antiviral therapy. In this study, comprising 757 patients with chronic hepatitis B from Europe and Asia, we found that higher viral load before initiation of treatment was a risk factor for relapse after stopping treatment. Patients with a low HBV DNA level before starting antiviral therapy had the lowest risk of relapse, and a high chance of HBsAg loss, after stopping treatment. These findings can help select patients for treatment withdrawal and guide intensity of off-treatment monitoring. |
format | Online Article Text |
id | pubmed-10362794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103627942023-07-23 Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study Sonneveld, Milan J. Chiu, Shao-Ming Park, Jun Yong Brakenhoff, Sylvia M. Kaewdech, Apichat Seto, Wai-Kay Tanaka, Yasuhito Carey, Ivana Papatheodoridi, Margarita Colombatto, Piero van Bömmel, Florian Berg, Thomas Zoulim, Fabien Ahn, Sang Hoon Dalekos, George N. Erler, Nicole S. Brunetto, Maurizia Wedemeyer, Heiner Cornberg, Markus Yuen, Man-Fung Agarwal, Kosh Boonstra, Andre Buti, Maria Piratvisuth, Teerha Papatheodoridis, George Chen, Chien-Hung Maasoumy, Benjamin JHEP Rep Research Article BACKGROUND & AIMS: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. METHODS: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA >2,000 IU/ml + alanine aminotransferase >2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal. RESULTS: We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (<20,000 IU/ml) in 150 (20%) and high (>20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels <20,000 IU/ml vs. 60% among patients with pretreatment HBV DNA levels >20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p <0.001). In multivariable analysis, pretreatment HBV DNA levels <20,000 IU/ml were independently associated with a reduced likelihood of clinical relapse (adjusted hazard ratio 0.379, p <0.001) and with an increased chance of HBsAg loss (adjusted hazard ratio 2.872, p <0.001). CONCLUSIONS: Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of end-of-treatment viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations. IMPACT AND IMPLICATIONS: A subgroup of patients with chronic hepatitis B may not require retreatment after stopping antiviral therapy. In this study, comprising 757 patients with chronic hepatitis B from Europe and Asia, we found that higher viral load before initiation of treatment was a risk factor for relapse after stopping treatment. Patients with a low HBV DNA level before starting antiviral therapy had the lowest risk of relapse, and a high chance of HBsAg loss, after stopping treatment. These findings can help select patients for treatment withdrawal and guide intensity of off-treatment monitoring. Elsevier 2023-05-12 /pmc/articles/PMC10362794/ /pubmed/37484211 http://dx.doi.org/10.1016/j.jhepr.2023.100790 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Sonneveld, Milan J. Chiu, Shao-Ming Park, Jun Yong Brakenhoff, Sylvia M. Kaewdech, Apichat Seto, Wai-Kay Tanaka, Yasuhito Carey, Ivana Papatheodoridi, Margarita Colombatto, Piero van Bömmel, Florian Berg, Thomas Zoulim, Fabien Ahn, Sang Hoon Dalekos, George N. Erler, Nicole S. Brunetto, Maurizia Wedemeyer, Heiner Cornberg, Markus Yuen, Man-Fung Agarwal, Kosh Boonstra, Andre Buti, Maria Piratvisuth, Teerha Papatheodoridis, George Chen, Chien-Hung Maasoumy, Benjamin Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study |
title | Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study |
title_full | Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study |
title_fullStr | Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study |
title_full_unstemmed | Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study |
title_short | Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study |
title_sort | lower pretreatment hbv dna levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with hbeag-negative chronic hepatitis b: a multicentre cohort study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362794/ https://www.ncbi.nlm.nih.gov/pubmed/37484211 http://dx.doi.org/10.1016/j.jhepr.2023.100790 |
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