HBV elimination in Africa—Current status and challenges

Abstract

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INTRODUCTION

HBV is endemic in Africa. Worldwide, 9 of the 17 countries accounting for 75% of the global HBV burden, are found in Africa.¹ In 2022, an estimated 64.8 (95% uncertainty interval [UI]: 52.8–80.8) million people were chronically infected, with an HBsAg-positive prevalence of 5.4% (95% UI: 4.4%–6.8%) in the WHO Africa region.¹ Of these, 3.6 (95% UI: 2.9–4.9) million children under the age of 5 years were HBsAg positive with a 1.7% (95% UI: 1.3–2.3) prevalence. This reflects a failure of maternal and child health services to effectively prevent mother-to-child transmission and early childhood HBV acquisition, associated with a chronicity risk of 90% and 30%–60%, respectively, as well as the ensuing later complications of cirrhosis and HCC.²

DISEASE BURDEN OF HEPATITIS B IN AFRICA

In Africa, 25% of people currently living with HBV are younger than 20 years of age. The spectrum of disease and natural history of chronic HBV infection are varied, with some remaining HBsAg-positive for life with no disease progression; others develop progressive liver fibrosis, cirrhosis, and end-stage liver disease. The risk of HCC is elevated.² Longitudinal study data suggest that, if left untreated, an 8%–20% cumulative risk of developing cirrhosis over 5 years exists.^3–6 Equally, HCC risk is high and ranges from a <1% to 5% annual risk. HCC survival in Africa is extraordinarily poor, with some recent data suggesting a median survival of 1.5 months after diagnosis.^7–9 Decompensated cirrhosis equally carries a poor prognosis, with 15%–40% survival at 5 years.¹⁰ Several host and viral factors alter risk and prognosis. These include male sex, a family history of HCC, cirrhosis, persistent HBeAg positivity, elevated HBsAg concentration, high HBV DNA viral load, HBV core-related antigen, HBV genotypes (genotype A subtype A1, genotype E, and genotype D), pre-core mutations (1862G→T and 1896G→A), basal core promoter mutations (1762A→T and 1764G→A), and aflatoxin exposure. All increase the rate of disease progression and the risk of developing HCC.^10–14

HIV-HBV and hepatitis D-HBV coinfection substantially increase the risk of cirrhosis and HCC. Almost 1.9 million people living with HIV-HBV and 1.6 million (95% CI: 1.1–2.5) living with hepatitis D-HBV coinfection reside in Africa, further increasing the HBV disease burden.¹⁵

The 2017 Global Burden of Disease study confirmed that sub-Saharan Africa (SSA) has the highest cirrhosis-related age-standardized death rate in the Global Burden of Disease super-regions with 32.2 (95% UI: 25.8–38.6) deaths per 100,000 with HBV being the leading causative factor.¹⁶ In Africa, 48.9% of cirrhotic deaths in Western Africa, 31.2% in Central Africa, 25.9% in Eastern Africa, and 21.9% in Southern Africa are HBV-related.¹⁶

HBV-related HCC presents at a median age of 42 years (34–51), is often aggressive with an overall mortality-to-incidence ratio of 0.95, and is frequently multifocal with vascular invasion at the time of presentation.¹⁷ A 2021 systematic analysis of 272 studies indicated that chronic hepatitis B accounted for 65.8% (95% CI: 39.1–68.3) and HBV-hepatitis D coinfection accounted for 14.8% (95% CI: 8.7–18.4) of viral hepatitis-related HCC in SSA.¹⁸ The age-standardized incident rates (per 100,000 individuals) of HBV-related HCC are highest in Western Africa at 4.35 (95% UI: 3.61–5.46), followed by Southern Africa (2.05; 95% UI: 1.84–2.31), Eastern Africa (1.89; 95% UI: 1.53–2.32), and Central Africa (1.76; 95% UI: 1.25–2.71). Palliative interventions are invariably the only management option available.¹⁹

CURRENT HEPATITIS B ELIMINATION PROGRESS IN AFRICA

Failure to prevent, diagnose, and treat chronic HBV infection are the major factors contributing to cirrhosis and HCC burden in Africa. Nucleoside analog treatment with the currently recommended tenofovir disoproxil fumarate or entecavir is highly effective and can delay the progression of cirrhosis, reduce the incidence of HCC, and improve long-term survival.¹¹ Furthermore, despite the HBV vaccine being available for more than 40 years, an estimated 990,000 (95% UI: 660,000–600,000) new HBV infections and 80,000 (95% UI: 47,000–110,000) HBV-related deaths occurred in 2019 in the WHO Africa region.²⁰

In 2023, the WHO AFRO region failed to reach the 2020 WHO Hepatitis B elimination goals targeting prevention, diagnosis, and treatment of hepatitis B of 30% diagnosed and treated, <1% HBsAg positivity in children under 5 years, 50% timely hepatitis B birth dose coverage, and 90% full 3-dose hepatitis B vaccine coverage, with the aim of reducing new chronic HBV infections to 20 per 100,000 and mortality to 10 per 100,000.²¹ This requires active identification and linkage to the care of those who live with HBV. It is mostly dependent on access to affordable diagnostics, particularly point-of-care tests for HBsAg and HBV DNA quantification molecular assays at the primary care level with clear pathways of referral for initiating and maintaining care.²²

The cornerstone of preventing HBV infection is the prevention of mother-to-child transmission and early childhood acquisition. Concerningly, in 2022, <1% of pregnant women with chronic hepatitis B have been treated. Only 14 (29%) African countries have implemented the hepatitis B birth dose vaccination with only 14% of neonates receiving timely hepatitis B birth dose coverage.^21,23 Full 3-dose hepatitis B vaccine coverage is 82%.¹ Projections for achieving targets of <0.1% HBsAg positivity in children <5 years of age by 2030 indicate that most countries globally not achieving this will be in Africa.

CURRENT CASCADE OF CARE AND TREATMENT IN AFRICA

In 2022, an estimated 5% of the almost 65 million people with chronic HBV infection in Africa were diagnosed, and of these, 2% were on treatment.¹ This equates to 2.61 million people with HBV diagnosed, and only 142,000 or 1% on treatment with an estimated 14.1 million eligible for treatment based on current criteria.²⁴ The consequence is that in 2022 almost 300,000 deaths occurred due to chronic HBV infection and its complications.¹

Screening and testing for hepatitis B remain wholly inadequate. To enhance screening, several upscaled interventions are required. A greater use of affordable and quality point-of-care HBV testing (several HBsAg tests are WHO prequalified) with this testing mostly happening at a capacitated primary level of care being essential. Defining who needs treatment requires HBV DNA point-of-care testing to stratify patients and link them to care more rapidly. Even so, capacity for HBV DNA quantification exists in that almost 7000 Xpert platforms are distributed in the African region, used mostly for Mycobacterium tuberculosis diagnostics (personal communication, 2024, Cepheid). These platforms are capable of running hepatitis B and C viral load quantification. Markers such as hepatitis B core-related antigen to guide care and offer an alternative have been assessed for use in practice in countries such as The Gambia in West Africa.²² Simplified models of care are required and countries, such as China, have embarked upon such strategies to upscale treatment by simplifying eligibility criteria.²⁵ A “treat all” or “test and treat” strategy based solely on HBsAg positivity has been suggested.²⁶ This has the appeal of vastly upscaling the initiation of patients on tenofovir. However, several barriers exist, including a lack of longitudinal data on the long-term retention in care of patients with chronic HBV, availability and access to tenofovir, and the limited ability of many health systems to accommodate an increased patient load, notably at the primary care level.^27,28. New guidance for the management of hepatitis B for low and middle-income countries, as anticipated, was published by the WHO in March 2024. It expands treatment criteria allowing for simplification of care at a primary level. and aims to extend treatment eligibility to an additional 50% of those requiring therapy.²⁹

Consequent to upscaled testing is the assessment of liver fibrosis. Real-time tools such as transient elastography, for example, FibroScan (Echosens) are available. In SSA, there are currently 88 machines available in 24 countries, but the equipment remains prohibitively expensive. Most North African countries have FibroScan available. The use of AST to Platelet Ratio Index and Fibrosis-4 scores is more readily available; however, most cutoff values for ruling in and ruling out cirrhosis have not included African populations in their validation. Recently, using a SSA cohort, an AST to Platelet Ratio IndexI rule-in threshold of >0.65 (set for transient elastography liver stiffness measurement >12.2 kPa) had a sensitivity of 56.2% and a specificity of 90% for predicting cirrhosis. A rule-out threshold of <0.6 had a sensitivity of 80.6% and a specificity of 64.3%.³⁰

The cost of the available generic nucleoside antivirals, such as tenofovir and entecavir, is no longer an absolute limiting factor for HBV management in Africa. Notably, tenofovir cost has declined; however, it is not always accessible or available to mono-infected patients with HBV given its use in externally funded HIV programs. Mono-infected patients with HBV often struggle to access tenofovir and incur out-of-pocket expenditures. In contrast, combination tenofovir/emtricitabine (eg, Truvada) used for HIV pre-exposure prophylaxis programs have been scaled up, enabling over 1 million people to access HIV pre-exposure prophylaxis in Africa.³¹ This does however offer a potential opportunity to enhance access and care to those with HBV mono-infection. The provision of HIV pre-exposure prophylaxis offers protection against HIV in an already high prevalence region while simultaneously offering HBV therapy. This approach requires increased investment in the infrastructure required to manage the additional caseload of patients and due caution to not overburden HIV services. It also provides a framework for the development of triple elimination services where HIV, HBV, and HCV screening and linkage to care can occur.³²

Hepatitis B in Africa is endemic, the burden substantial, and the current cascade of care suboptimal. While the tools to achieve elimination exist, success is only possible through a coordinated effort between governments, policymakers, and civil and patient advocacy groups, to overcome the current barriers to care. In 2018, 28 countries in Africa had national viral hepatitis elimination plans, with countries such as Rwanda leading the way on what can be achieved.³³ With Africa possessing the youngest population in the world (70% are <30 years old), the imperative to achieve a hepatitis B–free generation is immense (Table 1).

TABLE 1.

A snapshot of HBV in Africa

• 65 million Africans have chronic HBV infection • 3.6 million children <5 years of age are HBsAg positive • Most HBV transmission occurs horizontally before age 5 years among children with some contribution from vertical mother-to-child transmission • Almost 1 million new HBV infections occur annually • The highest age-standardized cirrhosis-related death rate is in sub-Saharan Africa • HCC risk is significant, clinical presentation late, and survival rates poor • 5% are diagnosed—2% are on treatment • <1% of pregnant women are on treatment • 14 African countries (29%) have introduced Hep B birth dose vaccination • Elimination targets for 2030 will not be achieved • Focused and novel interventions are required to improve diagnosis, linkage to treatment, and expansion of prevention of mother-to-child transmission