TY - JOUR
T1 - Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants
AU - Thompson, Alexander J.
AU - Jackson, Kathy
AU - Bonanzinga, Sara
AU - Hall, Sam A.L.
AU - Hume, Simon
AU - Burns, Gareth S.
AU - Sundararajan, Vijaya
AU - Ratnam, Dilip
AU - Levy, Miriam T.
AU - Lubel, John
AU - Nicoll, Amanda J.
AU - Strasser, Simone I.
AU - Sievert, William
AU - Desmond, Paul V.
AU - Ngu, Meng C.
AU - Sinclair, Marie
AU - Meredith, Christopher
AU - Matthews, Gail
AU - Revill, Peter A.
AU - Littlejohn, Margaret
AU - Bowden, D. Scott
AU - Canchola, Jesse A.
AU - Torres, Jason
AU - Siew, Philip
AU - Lau, Jasmin
AU - Brot, Benjamin La
AU - Kuchta, Alison
AU - Visvanathan, Kumar
N1 - Funding Information:
The authors thank the patients who participated in the study. Manuscript preparation was supported by Data First Consulting, Inc. (Sebastopol, CA) and funded by Roche Molecular Systems.
Funding Information:
Amanda J. Nicoll advises and is on the speakers’ bureau for Ipsen, Eisai, Roche, and AstraZeneca. Simone I. Strasser advises and is on the speakers’ bureau for Gilead, Eisai, Norgine, Roche, Chiesi, and AstraZeneca. She advises Pfizer and MSD and is on the speakers’ bureau for Otsuka and AbbVie. Gail Matthews advises and received grants from Gilead and ViiV. She advises AstraZeneca and received grants from AbbVie. Kumar Visvanathan consults, advises, and is on the speakers’ bureau for Gilead. He advises ViiV. The remaining authors have no conflicts to report.
Funding Information:
The authors thank the patients who participated in the study. Manuscript preparation was supported by Data First Consulting, Inc. (Sebastopol, CA) and funded by Roche Molecular Systems. The clinical study was supported by the National Health and Medical Research Council of Australia Project Grant 1066536. Additional support for data extraction was provided by Roche Molecular Systems, Inc. Alexander Thompson received funding from the National Health and Medical Research Council of Australia (MRFF Practitioner Fellowship 1142976). cobas® 6800/8800 HBV RNA Investigational Assay reagents were provided by Roche Molecular Systems, Inc.
Funding Information:
The clinical study was supported by the National Health and Medical Research Council of Australia Project Grant 1066536. Additional support for data extraction was provided by Roche Molecular Systems, Inc. Alexander Thompson received funding from the National Health and Medical Research Council of Australia (MRFF Practitioner Fellowship 1142976). cobas® 6800/8800 HBV RNA Investigational Assay reagents were provided by Roche Molecular Systems, Inc.
Publisher Copyright:
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.
PY - 2023/8
Y1 - 2023/8
N2 - Background and Aims: HBV RNA in peripheral blood reflects HBV cccDNA transcriptional activity and may predict clinical outcomes. The prospective Melbourne HBV-STOP trial studied nucleot(s)ide analog discontinuation in HBeAg-negative non-cirrhotic participants with long-term virological suppression. Ninety-six weeks after stopping treatment, the proportion of participants with virological relapse (HBV DNA > 2000 IU/mL), biochemical relapse (ALT > 2 × ULN and HBV DNA > 2000 IU/mL), or hepatitis flare (ALT > 5 × ULN and HBV DNA > 2000 IU/mL) was 89%, 58%, and 38%, respectively. We evaluated the ability of serum HBV RNA levels to predict these outcomes. Approach & Results: HBV RNA levels were measured using the Roche cobas 6800/8800 HBV RNA Investigational Assay. Sixty-five participants had baseline and longitudinal off-treatment specimens available for RNA testing. HBV RNA was detectable at baseline in 25% of participants and was associated with a higher risk of biochemical relapse (81% vs. 51%, p value 0.04) and hepatitis flare (63% vs. 31%, p value 0.04). Participants who had undetectable serum HBV RNA as well as HBsAg ≤ 100 IU/mL at baseline were less likely to experience virological relapse (4 of 9, 44%) than participants with detectable HBV RNA and HBsAg level > 100 IU/mL (15/15, 100%; p value 0.0009). Off-treatment levels of HBV RNA were correlated with HBV DNA and were associated with the risk of hepatitis flare. Conclusions: Serum HBV RNA may be a useful biomarker for guiding clinical decision-making before stopping nucleot(s)ide analog therapy. Baseline HBV RNA and HBsAg levels are associated with the risk of clinical relapse, hepatitis flare, and disease remission off-treatment.
AB - Background and Aims: HBV RNA in peripheral blood reflects HBV cccDNA transcriptional activity and may predict clinical outcomes. The prospective Melbourne HBV-STOP trial studied nucleot(s)ide analog discontinuation in HBeAg-negative non-cirrhotic participants with long-term virological suppression. Ninety-six weeks after stopping treatment, the proportion of participants with virological relapse (HBV DNA > 2000 IU/mL), biochemical relapse (ALT > 2 × ULN and HBV DNA > 2000 IU/mL), or hepatitis flare (ALT > 5 × ULN and HBV DNA > 2000 IU/mL) was 89%, 58%, and 38%, respectively. We evaluated the ability of serum HBV RNA levels to predict these outcomes. Approach & Results: HBV RNA levels were measured using the Roche cobas 6800/8800 HBV RNA Investigational Assay. Sixty-five participants had baseline and longitudinal off-treatment specimens available for RNA testing. HBV RNA was detectable at baseline in 25% of participants and was associated with a higher risk of biochemical relapse (81% vs. 51%, p value 0.04) and hepatitis flare (63% vs. 31%, p value 0.04). Participants who had undetectable serum HBV RNA as well as HBsAg ≤ 100 IU/mL at baseline were less likely to experience virological relapse (4 of 9, 44%) than participants with detectable HBV RNA and HBsAg level > 100 IU/mL (15/15, 100%; p value 0.0009). Off-treatment levels of HBV RNA were correlated with HBV DNA and were associated with the risk of hepatitis flare. Conclusions: Serum HBV RNA may be a useful biomarker for guiding clinical decision-making before stopping nucleot(s)ide analog therapy. Baseline HBV RNA and HBsAg levels are associated with the risk of clinical relapse, hepatitis flare, and disease remission off-treatment.
KW - Humans Antiviral Agents/therapeutic use DNA, Viral Hepatitis B e Antigens Hepatitis B Surface Antigens Hepatitis B virus/genetics Hepatitis B, Chronic/drug therapy Nucleosides/therapeutic use Prospective Studies Rna Symptom Flare Up
UR - http://www.scopus.com/inward/record.url?scp=85188159570&partnerID=8YFLogxK
U2 - 10.1097/HC9.0000000000000188
DO - 10.1097/HC9.0000000000000188
M3 - Article
C2 - 37459199
AN - SCOPUS:85188159570
SN - 2471-254X
VL - 7
JO - Hepatology Communications
JF - Hepatology Communications
IS - 8
M1 - e0188
ER -
