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Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139‐Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection
The nucleic acid polymer REP 2139 inhibits assembly/secretion of hepatitis B virus (HBV) subviral particles. Previously, REP 2139‐Ca and pegylated interferon (pegIFN) in HBV/hepatitis delta virus (HDV) coinfection achieved high rates of HDV RNA and hepatitis B surface antigen (HBsAg) loss/seroconver...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850315/ https://www.ncbi.nlm.nih.gov/pubmed/33553968 http://dx.doi.org/10.1002/hep4.1633 |
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author | Bazinet, Michel Pântea, Victor Cebotarescu, Valentin Cojuhari, Lilia Jimbei, Pavlina Anderson, Mark Gersch, Jeff Holzmayer, Vera Elsner, Carina Krawczyk, Adalbert Kuhns, Mary C. Cloherty, Gavin Dittmer, Ulf Vaillant, Andrew |
author_facet | Bazinet, Michel Pântea, Victor Cebotarescu, Valentin Cojuhari, Lilia Jimbei, Pavlina Anderson, Mark Gersch, Jeff Holzmayer, Vera Elsner, Carina Krawczyk, Adalbert Kuhns, Mary C. Cloherty, Gavin Dittmer, Ulf Vaillant, Andrew |
author_sort | Bazinet, Michel |
collection | PubMed |
description | The nucleic acid polymer REP 2139 inhibits assembly/secretion of hepatitis B virus (HBV) subviral particles. Previously, REP 2139‐Ca and pegylated interferon (pegIFN) in HBV/hepatitis delta virus (HDV) coinfection achieved high rates of HDV RNA and hepatitis B surface antigen (HBsAg) loss/seroconversion in the REP 301 study (NCT02233075). The REP 301‐LTF study (NCT02876419) examined safety and efficacy during 3.5 years of follow‐up. In the current study, participants completing therapy in the REP 301 study were followed for 3.5 years. Primary outcomes were safety and tolerability, and secondary outcomes were HDV functional cure (HDV RNA target not detected [TND], normal alanine aminotransferase [ALT]), HBV virologic control (HBV DNA ≤2,000 IU/mL, normal ALT), HBV functional cure (HBV DNA TND; HBsAg <0.05 IU/mL, normal ALT), and HBsAg seroconversion. Supplemental analysis included high‐sensitivity HBsAg (Abbott ARCHITECT HBsAg NEXT), HBV pregenomic RNA (pgRNA), HBsAg/hepatitis B surface antibody (anti‐HBs) immune complexes (HBsAg ICs), and hepatitis B core‐related antigen (HBcrAg). Asymptomatic grade 1‐2 ALT elevations occurred in 2 participants accompanying viral rebound; no other safety or tolerability issues were observed. During therapy and follow‐up, HBsAg reductions to <0.05 IU/mL were also <0.005 IU/mL. HBsAg ICs declined in 7 of 11 participants during REP 2139‐Ca monotherapy and in 10 of 11 participants during follow‐up. HDV functional cure persisted in 7 of 11 participants; HBV virologic control persisted in 3 and functional cure (with HBsAg seroconversion) persisted in 4 of these participants. Functional cure of HBV was accompanied by HBV pgRNA TND and HBcrAg <lower limit of quantitation. Conclusion: REP 2139‐Ca + pegIFN is not associated with long‐term safety or tolerability issues. The establishment of HDV functional cure and HBV virologic control/functional cure and HBsAg seroconversion are durable over 3.5 years and may reflect removal of integrated HBV DNA from the liver. Further investigation is warranted in larger studies. |
format | Online Article Text |
id | pubmed-7850315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78503152021-02-05 Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139‐Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection Bazinet, Michel Pântea, Victor Cebotarescu, Valentin Cojuhari, Lilia Jimbei, Pavlina Anderson, Mark Gersch, Jeff Holzmayer, Vera Elsner, Carina Krawczyk, Adalbert Kuhns, Mary C. Cloherty, Gavin Dittmer, Ulf Vaillant, Andrew Hepatol Commun Original Articles The nucleic acid polymer REP 2139 inhibits assembly/secretion of hepatitis B virus (HBV) subviral particles. Previously, REP 2139‐Ca and pegylated interferon (pegIFN) in HBV/hepatitis delta virus (HDV) coinfection achieved high rates of HDV RNA and hepatitis B surface antigen (HBsAg) loss/seroconversion in the REP 301 study (NCT02233075). The REP 301‐LTF study (NCT02876419) examined safety and efficacy during 3.5 years of follow‐up. In the current study, participants completing therapy in the REP 301 study were followed for 3.5 years. Primary outcomes were safety and tolerability, and secondary outcomes were HDV functional cure (HDV RNA target not detected [TND], normal alanine aminotransferase [ALT]), HBV virologic control (HBV DNA ≤2,000 IU/mL, normal ALT), HBV functional cure (HBV DNA TND; HBsAg <0.05 IU/mL, normal ALT), and HBsAg seroconversion. Supplemental analysis included high‐sensitivity HBsAg (Abbott ARCHITECT HBsAg NEXT), HBV pregenomic RNA (pgRNA), HBsAg/hepatitis B surface antibody (anti‐HBs) immune complexes (HBsAg ICs), and hepatitis B core‐related antigen (HBcrAg). Asymptomatic grade 1‐2 ALT elevations occurred in 2 participants accompanying viral rebound; no other safety or tolerability issues were observed. During therapy and follow‐up, HBsAg reductions to <0.05 IU/mL were also <0.005 IU/mL. HBsAg ICs declined in 7 of 11 participants during REP 2139‐Ca monotherapy and in 10 of 11 participants during follow‐up. HDV functional cure persisted in 7 of 11 participants; HBV virologic control persisted in 3 and functional cure (with HBsAg seroconversion) persisted in 4 of these participants. Functional cure of HBV was accompanied by HBV pgRNA TND and HBcrAg <lower limit of quantitation. Conclusion: REP 2139‐Ca + pegIFN is not associated with long‐term safety or tolerability issues. The establishment of HDV functional cure and HBV virologic control/functional cure and HBsAg seroconversion are durable over 3.5 years and may reflect removal of integrated HBV DNA from the liver. Further investigation is warranted in larger studies. John Wiley and Sons Inc. 2020-11-13 /pmc/articles/PMC7850315/ /pubmed/33553968 http://dx.doi.org/10.1002/hep4.1633 Text en © 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Bazinet, Michel Pântea, Victor Cebotarescu, Valentin Cojuhari, Lilia Jimbei, Pavlina Anderson, Mark Gersch, Jeff Holzmayer, Vera Elsner, Carina Krawczyk, Adalbert Kuhns, Mary C. Cloherty, Gavin Dittmer, Ulf Vaillant, Andrew Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139‐Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection |
title | Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139‐Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection |
title_full | Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139‐Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection |
title_fullStr | Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139‐Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection |
title_full_unstemmed | Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139‐Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection |
title_short | Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139‐Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection |
title_sort | persistent control of hepatitis b virus and hepatitis delta virus infection following rep 2139‐ca and pegylated interferon therapy in chronic hepatitis b virus/hepatitis delta virus coinfection |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850315/ https://www.ncbi.nlm.nih.gov/pubmed/33553968 http://dx.doi.org/10.1002/hep4.1633 |
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