Hepatitis B virus RNA decline without concomitant viral antigen decrease is associated with a low probability of sustained response and hepatitis B surface antigen loss
Sylvia M Brakenhoff 1 , Robert A de Man 1 , André Boonstra 1 , Margo J H van Campenhout 1 , Robert J de Knegt 1 , Florian van Bömmel 2 , Annemiek A van der Eijk 3 , Thomas Berg 2 , Bettina E Hansen 4 5 , Harry L A Janssen 4 , Milan J Sonneveld 1
Affiliations
Affiliations
1
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
2
Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
3
Department of Viroscience, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
4
Toronto Center for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, ON, Canada.
5
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
PMID: 33222190 DOI: 10.1111/apt.16172
Abstract
Background: Serum hepatitis B virus (HBV) RNA may reflect intrahepatic HBV replication. Novel anti-viral drugs have shown potent HBV RNA decline without concomitant hepatitis B surface antigen (HBsAg) decrease. How this relates to off-treatment response is yet unclear.
Aim: To study the degree of on-treatment viral antigen decline among patients with pronounced HBV RNA decrease in relation to off-treatment sustained response and HBsAg loss.
Methods: HBV RNA, HBsAg and hepatitis B core-related antigen (HBcrAg) were quantified in patients with chronic hepatitis B who participated in two randomised controlled trials of peginterferon-based therapy. Sustained response (HBV DNA <2000 IU/mL) and/or HBsAg loss were assessed in patients with and without on-treatment HBV RNA response (either >2 log HBV RNA decline or >1 log decline resulting in an undetectable value at on-treatment week 24), stratified by concomitant HBsAg decline (<0.5/0.5-1/>1 log).
Results: We enrolled 279 patients; 176 were hepatitis B e antigen (HBeAg)-positive, and 103 were HBeAg-negative. Sustained response was achieved in 20.4% of patients. At on-treatment week 24, HBV RNA response was associated with higher sustained response rates (27.4% vs 13.0% in non-responders, P = 0.004). However, among patients with an HBV RNA response (n = 135), 56.4% did not experience >0.5 log HBsAg decline. Among HBV RNA responders, sustained response was achieved in 47.6% of those with >1 log HBsAg decline (n = 20/42), vs 16.0% with <0.5 log decline (n = 12/75, P = 0.001). Similar results were obtained with HBcrAg and when response was defined as HBsAg loss.
Conclusions: In this cohort, many patients with HBV RNA response during peginterferon-based treatment did not experience HBsAg and/or HBcrAg decline. The absence of concomitant decline in these viral antigens was associated with low rates of treatment response and HBsAg loss. Future trials should therefore consider kinetics of combined biomarkers to assess anti-viral efficacy. Trial registration, ClinicalTrials.gov: NCT00114361, NCT00146705.
乙型肝炎病毒RNA下降而病毒抗原没有减少的情况与持续应答和乙型肝炎表面抗原丢失的可能性低相关
西尔维亚·M·布雷肯霍夫（Sylvia M Brakenhoff）1，罗伯特·阿德曼（Robert A de Man）1，安德烈·邦斯特拉（AndréBoonstra）1，玛格·霍格（Margo JH van Campenhout）1，罗伯特·德·克内格特（Robert J de Knegt）1，弗洛里安·范博默尔（Florian vanBömmel）2，安妮米克·范·范·艾克（Annemiek A van der Eijk）3，托马斯·伯格2，贝蒂娜·汉森（Bettina E Hansen）4 5，哈里洛杉矶詹森4号，米兰·索内维尔德1
隶属关系
隶属关系