Role of Core/Capsid Inhibitors in Functional Cure Strategies for Chronic Hepatitis B
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HEPATITIS B (JK LIM, SECTION EDITOR)
Role of Core/Capsid Inhibitors in Functional Cure Strategies for Chronic Hepatitis B Rex Wan-Hin Hui 1 & Lung-Yi Mak 1 & Wai-Kay Seto 1,2 & Man-Fung Yuen 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Functional cure of chronic hepatitis B (CHB), defined as sustained hepatitis B surface antigen (HBsAg) seroclearance, is associated with favourable clinical outcomes. Nonetheless, the functional cure is rarely achievable by current treatment modalities. Core/capsid inhibitors (core protein allosteric modulators, CpAMs) are a novel drug class that targets the hepatitis B core protein and may have a potential impact on the functional cure. This article reviews the preclinical and clinical results of CpAMs. Recent Findings CpAMs interfere with the hepatitis B virus (HBV) nucleocapsid assembly and also exert a secondary action on covalently closed circular DNA replenishment. CpAMs are able to sustainably suppress hepatitis B viral load and viral antigens in in vivo studies. In phase I/II clinical trials, CpAMs are well tolerated and are efficacious in suppressing viral replication. CpAMs also have synergistic antiviral effects when combined with nucleoside analogues or pegylated interferon. The clinical data has yet to demonstrate the capability of CpAMs in inducing HBsAg seroclearance, possibly due to the short follow-up period of current studies. There is emerging data showing initial viral antigen reduction with the continuation of CpAMs for more than 24 weeks. Summary CpAMs have shown promising preclinical and phase I/II clinical data. Data from long-term phase III trials and from combination therapies with other antiviral agents are keenly anticipated. Keywords Antiviral therapy . Chronic hepatitis B . Core protein allosteric modulator . Functional cure . Hepatitis B core antigen
Background Chronic hepatitis B infection (CHB) has a global prevalence of 3.9% (292 million patients) [1] and causes substantial liverrelated morbidity and mortality [2]. In 2016, the World Health Organization (WHO) established the goal for the elimination of viral hepatitis (including hepatitis B) as a public health threat by 2030 [3]. Preventive strategies, particularly through hepatitis B vaccination and hepatitis B immunoglobulin, have been successful in reducing the incidence of newly acquired This article is part of the Topical Collection on Hepatitis B * Man-Fung Yuen [email protected] 1
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Road 102, Pokfulam, Hong Kong
2
State Key Laboratory of Liver Research, The University of Hong Kong, Road 102, Pokfulam, Hong Kong
hepatitis B infection, and the prevalence of CHB in children younger than 5 years old has dropped from 4.7 to 1.3% [4]. With effective preventive strategies in place, the relative importance of treating currently infected CHB patients will rise correspondingly. The complete cure of CHB is difficult due to the persistence of hepatitis B virus (HBV) cova
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