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Pathway to global elimination of hepatitis B:
HBV cure is just the first step
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Hepatology Sept 2023
"Implementation of future HBV cure will be a challenge, hampered by the chronic nature of infection, high levels of endemicity in low- and middle-income countries, and the likely requirement for multiple agents from different drug classes possibly with parenteral routes of administration to achieve cure.
Global rates of diagnosis, linkage to care, and treatment remain well below what is required to achieve the WHO 2030 targets and scale-up future HBV cure globally.
HBV cure will likely take the form of a synergistic combination of drugs with different mechanisms of action to reduce high levels of HBV replication, restore HBV-specific immune function, and counter virological resistance.5,8,9 The current main drug classes under investigation are outlined in Table 1 and include direct antivirals that target multiple aspects of the HBV lifecycle and immune-stimulating therapies. These agents target HBsAg production, reduce HBV DNA and RNA transcription, or directly stimulate the host immune response against HBV via innate or adaptive immune signaling pathways.8,9
Currently, several early-phase drugs for HBV cure are delivered subcutaneously or intravenously,5 which would present major barriers to universal delivery in most countries with intermediate to high HBV prevalence. Moreover, immunotherapies may require personalized approaches and/or frequent monitoring of treatment to prevent unwanted hepatic flares."
A treat-all strategy is already the mainstay of therapy for people with HBV-HIV coinfection, where it is often started in the immune-tolerant phase, including in childhood. 79 Importantly, among coinfected people who commenced tenofovir before the age of 46 years, annual HCC incidence is very low, well below the current annual incidence threshold where HCC surveillance is considered cost-effective.79 This suggests that significant HCC surveillance costs may be averted by early treatment of HBV in childhood or early adulthood."
CONCLUSIONS
The path toward HBV elimination is becoming clearer, illuminated by promising HBV cure research. However, the cure is only one part of the solution to achieve HBV elimination globally. The groundwork for a cure must begin now with the optimization of current tools to improve the HBV cascade of care and facilitate rapid upscale of cure when it becomes available. However, we must also continue to work toward HBV elimination with the safe, effective, and affordable vaccine and treatments that we already have to achieve HBV mortality targets by 2030. We must proactively prepare, but not wait, for the HBV cure.
Abstract
Hepatitis B (HBV) is a major cause of global morbidity and mortality, and the leading cause of liver cancer worldwide. Significant advances have recently been made toward the development of a finite HBV treatment that achieves permanent loss of HBsAg and HBV DNA (so-called "HBV cure"), which could provide the means to eliminate HBV as a public health threat. However, the HBV cure is just one step toward achieving WHO HBV elimination targets by 2030, and much work must be done now to prepare for the successful implementation of the HBV cure. In this review, we describe the required steps to rapidly scale-up future HBV cure equitably. We present key actions required for successful HBV cure implementation, integrated within the World Health Organization (WHO) Global Health Sector Strategy (GHSS) 2022–2030 framework. Finally, we highlight what can be done now to progress toward the 2030 HBV elimination targets using available tools to ensure that we are preparing, but not waiting, for the cure.
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