Abstract

Hepatitis D is the smallest virus known to infect humans, the most aggressive, causing the most severe disease. It is considered a satellite or defective virus requiring the hepatitis B surface antigen (HBsAg) for its replication with approximately 10–70 million persons infected. Elimination of hepatitis D is, therefore, closely tied to hepatitis B elimination. There is a paucity of quality data in many resource-poor areas. Despite its aggressive natural history, treatment options for hepatitis D to date have been limited and, in many places, inaccessible. For decades, Pegylated interferon alpha (Peg IFN α) offered limited response rates (20%) where available. Developments in understanding viral replication pathways has meant that, for the first time in over three decades, specific therapy has been licensed for use in Europe. Bulevirtide (Hepcludex®) is an entry inhibitor approved for use in patients with confirmed viraemia and compensated disease. It can be combined with Peg IFN α and/or nucleos(t)ide analogue for hepatitis B. Early reports suggest response rates of over 50% with good tolerability profile. Additional agents showing promise include the prenylation inhibitor lonafarnib, inhibitors of viral release (nucleic acid polymers) and better tolerated Peg IFN lambda (λ). These agents remain out of reach for most resource limited areas where access to new therapies are delayed by decades. strategies to facilitate access to care for the most vulnerable should be actively sought by all stakeholders.

Highlights

  • Hepatitis delta virus (HDV), discovered over 40 years ago by Mario Rizzetto [1], is a small, enveloped RNA virus

  • The HDV virion consists of a shared envelope protein with hepatitis B virus (HBV), and a ribonucleoprotein containing the viral genome of circular single-stranded RNA [2]

  • HDV enters hepatocytes through the same mechanism as HBV due to their shared envelope protein [3]

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Summary

Introduction

Hepatitis delta virus (HDV), discovered over 40 years ago by Mario Rizzetto [1], is a small, enveloped RNA virus. There are approximately 250 million people worldwide with hepatitis B [4], and approximately 5% of HBsAg-positive individuals are estimated to have HDV [4]. Universal testing for HDV in HBsAg-positive individuals is not widely recommended or available, contributing to likely underestimates of its true prevalence. Guidelines from Europe (EASL) and the Asia Pacific Region (APASL) recommend testing for HDV for all HBsAg-positive individuals [8,9]. American guidelines (AASLD) recommend screening in key populations at risk of HDV such as those with risk factors or born in high endemic regions, or HBsAg-positive individuals with low or undetectable HBV DNA but elevated ALT levels [10]. We highlight the epidemiology, natural history, diagnostics, and treatment options for HDV, with a focus on resource-limited settings

Epidemiology
Natural History
Diagnosis
Treatment
Newer Treatments under Evaluation
Summary and Recommendations
Findings
Key Summary of Recommendations
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