Epidemiology, presentation, and therapeutic approaches for hepatitis D infections

ABSTRACT

Introduction

Chronic Hepatitis D virus (HDV) infection remains an important global public health problem, with a changing epidemiological landscape over the past decade along with widespread implementation of hepatitis B vaccination and human migration. The landscape of HDV treatments has been changing, with therapies that have been under development for the last decade now in late stage clinical trials. The anticipated availability of these new therapies will hopefully replace the current therapies which are minimally effective.

Areas covered

This narrative review discusses the clinical course, screening and diagnosis, transmission risk factors, epidemiology, current and investigational therapies, and liver transplantation in HDV. Literature review was performed using PubMed and ClinicalTrials.gov and includes relevant articles from 1977 to 2022.

Expert opinion

HDV infection is an important global public health issue with a true prevalence that is still unknown. The distribution of HDV infection has changed globally with the availability of HBV vaccination and patterns of human migration. As HDV infection is associated with accelerated disease courses and poor outcomes, the global community needs to agree upon a uniform HDV screening strategy to understand the truth of global prevalence such that new therapies can target appropriate individuals as they become available in the future.

KEYWORDS:

• Anti-viral therapy
• Epidemiology
• Hepatitis Delta
• Bulevirtide
• Interferon

Article highlights

• New and improved hepatitis D screening and diagnostic tests have been developed, including those that can detect all genotypes.

• The epidemiology of hepatitis D infection is changing with the variability of hepatitis B vaccination implementation and patterns of human migration.

• There are no FDA-approved therapies against chronic hepatitis D infection, which accelerates cirrhosis and can lead to hepatocellular carcinoma. The traditional therapeutic approach towards chronic HDV infection of interferons was adopted from other chronic hepatitis viral infections. Interferons have significant adverse effects and a known late relapse off-therapy.

• Bulevirtide, an entry inhibitor, has been granted conditional marketing authorization by European Medicines Agency approval but has yet to be authorized for use in the United States.

• Several new investigational agents ranging from lonafarnib to immune checkpoint inhibitors are being studied against HDV, raising hopes for the availability of more effective therapies in the near future.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

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

Author Contributions

Guarantor of article: CK. Concept and Design: HB, MK, TH, CK. Acquisition of Data: HB, MK, TH, CK. Statistical Analysis and Interpretation of Data: HB, MK, TH, CK. Drafting and Revision of Manuscript: HB, MK, TH, CK

Additional information

Funding

This paper was funded by the Intramural Research Programs of the National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health.