Novel developments of hepatitis B: treatment goals, agents and monitoring tools

ABSTRACT

Introduction: Chronic hepatitis B (CHB) infection causes considerable morbidity and mortality and hence should be a target for global elimination. In recent years, advances have been made in understanding the disease pathophysiology and the relationship to clinical outcome. Novel treatment targets are actively being sought in the hope of improving the treatment outlook.

Areas covered: We discussed the cascade of cure of CHB with respect to the degree of persistence of viral genome and proteins. Several novel antiviral agents either targeting the virus or the host are in different clinical phases of development. Serum hepatitis B core-related antigen and HBV RNA are novel markers, which might have a role in the prediction of specific clinical outcomes such as development of hepatocellular carcinoma or virological relapse after cessation of antiviral therapy. These markers may also be used to monitor treatment response in the drug trials.

Expert commentary: Global elimination of CHB is challenged by extremely low awareness of illness and poor access to care. CHB and its related complications can be reduced by birth dose vaccine, antiviral therapy, and alleviated by complication screening. Treatment options for CHB will expand in the next decade and early functional cure is not an impractical goal.

KEYWORDS:

• Antiviral therapy
• cirrhosis
• core protein allosteric modulator
• covalently closed circular DNA
• cure
• genome editing
• global elimination
• hepatitis B core-related antigen
• hepatitis B virus
• hepatocellular carcinoma
• HBV RNA
• immunomodulator
• integrated DNA
• prevention
• programmed cell death protein 1
• RNA interfering gene silencer
• therapeutic vaccine
• vaccination
• viral entry inhibitor

Article highlights

• Globally, the challenge of elimination chronic hepatitis B (CHB) is largely contributed by poor awareness of the infection and limited access to care.

• Prevention of CHB and its related complications can be facilitated by birth-dose vaccine, antiviral prophylaxis in viremic mothers, effective antiviral therapy, and regular complication screening.

• Treatment endpoints of CHB are defined in a cascade of cure: partial cure, functional cure, complete cure, and sterilizing cure.

• Novel antiviral agents with alternative mechanisms of action are in clinical phase of development to enhance functional cure of CHB.

• Novel markers, including hepatitis B core-related antigen (HBcrAg) and HBV RNA, are invaluable for treatment monitoring in drug trials, as well as the prediction of disease outcomes in CHB.

Declaration of interest

WK Seto is an advisory board member of Gilead Sciences and Bristol-Myers Squibb and received speaker fees from Gilead Sciences, Bristol-Myers Squibb and Novartis. J Fung received research funding from Novartis. MF Yuen received speaker fees from GlaxoSmithKline, Bristol-Myers Squibb, Novartis, and Gilead Sciences; and received research funding and is an advisory board member of Bristol-Myers Squibb, Novartis and Gilead Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.