COVID-19 is hampering progress in eliminating hepatitis B virus (HBV) by 2030, less than 10 years away. According to a new modelling study conducted by Imperial College London in collaboration with World Health Organisation (WHO), disruptions to the hepatitis B vaccination programme due to the pandemic could have a serious impact on efforts to reach the targets of the global strategy.
Under a worst-case scenario, with high levels of disruptions of both the birth dose and childhood HBV immunisation (by 60% and 20% for one year respectively), as well as a delay and slow recovery in the expansion of the vaccination programme towards the planned 2030 WHO-targets in the post-COVID-19 period, there will be a projected 5.3 million additional chronic HBV infections among children born between 2020 and 2030 and one million additional HBV-related deaths among those children later on. Missing opportunities to prevent new HBV infections will have a long-lasting and life-impacting effect.
The proportion of children under five years of age chronically infected with hepatitis B dropped to just under one percent in 2019 down from around five percent in the pre-vaccine era (the period between the 1980s and the early 2000s), according to new estimates from WHO.
This marks the achievement of one of the milestone targets to eliminate viral hepatitis in the Sustainable Development Goals ─ to reach under one percent prevalence of HBV infections in children under five years of age by 2020.
“No infant should grow up only to die of hepatitis B because they were not vaccinated ─ today’s milestone means that we have dramatically reduced the number of cases of liver damage and liver cancer in future generations”, says Dr Tedros Adhanom Ghebreyesus.
“Preventing mother-to-child transmission of hepatitis B is the most important strategy for controlling the disease and saving lives. Even in the midst of the COVID-19 pandemic, we must ensure that mothers and newborns have access to life-saving services including hepatitis B vaccinations.”
On World Hepatitis Day 2020, WHO was calling for united and stepped-up action to build on this achievement through intensified efforts to prevent mother-to-child transmission of HBV through testing pregnant women and provision of antiviral prophylaxis to those who need it and maintaining and expanding access to hepatitis B immunization and birth dose vaccine.
Globally, more than 250 million people are living with chronic HBV infection. Infants are especially vulnerable: about 90% of children infected with HBV in their first year of life become chronic HBV carriers.
HBV attacks the liver and claims the lives of nearly 900 000 people each year.
Preventing hepatitis B
Infants can be protected from HBV through a safe and effective vaccine that provides over 95% protection against infection. WHO recommends that all infants receive a first dose of the hepatitis B vaccine as soon as possible after birth – preferably within 24 hours – followed by at least 2 additional doses.
The scale-up of hepatitis B vaccine worldwide over the last two decades, which has been in large part due to the support provided by Gavi, the Vaccine Alliance, has been a great public health success story and contributed to the decrease in HBV infections among children.
In 2019, coverage of three doses of the hepatitis B vaccine during childhood reached 85% worldwide, up from around 30% in 2000. However, access to the first critical dose within 24 hours of birth remains uneven. Global coverage of this birth dose is 43%, but this drops to 34% in the WHO Eastern Mediterranean Region and only 6% in the WHO African Region.
Director of Global HIV, Hepatitis and STI Programmes, Dr Meg Doherty, says “expanding access to a timely birth dose of the hepatitis B vaccine is the cornerstone of efforts to prevent mother-to-children transmission of HBV. For countries especially in regions such as Sub-Saharan Africa, where the birth dose of hepatitis B vaccine has not yet been introduced, it is a priority to assure that protection as early as possible.”
An additional way to protect children is to provide pregnant women with antiviral treatment to reduce mother-to-child transmission of HBV. WHO already recommends routine testing of all pregnant women for HBV, as well as HIV and syphilis as early as possible in their pregnancy. In view of new evidence on the safety and efficacy of antiviral prophylaxis in pregnant women and their children, WHO has issued two new recommendations.
Pregnant women who test positive for hepatitis B infection and have a high level of HBV in the blood (known as HBV viral load) should receive preventive antiviral therapy with tenofovir from the 28th week of pregnancy until birth. The antiviral drug, tenofovir is available at low cost in many countries of the world for less than $3.00 per month.
In settings where HBV viral load testing is not available, WHO recommends the use of an alternative low-cost test (HBeAg) to determine whether a woman is eligible for preventive antiviral therapy.
In countries that have already achieved high coverage of hepatitis B immunization, including timely birth dose, routine testing for HBV infection among pregnant women and antiviral prophylaxis for those in need is an additional opportunity to prevent onward transmission from mother to child.
“Stopping vertical transmission of HBV is a key pillar of the global ‘triple elimination’ initiative, which seeks to eliminate mother-to-child transmission of three infections that are prevalent in low- and middle-income countries: HIV, syphilis and hepatitis B virus”, adds Dr Doherty.
Eliminating mother-to-child transmission of HBV is also an important stepping stone for reaching the targets of WHO’s global hepatitis strategy, which aims to reduce new hepatitis infections by 90% and deaths by 65%, compared to 2015 levels.
WHO has announced additional efforts to eliminate hepatitis by 2030. The overall strategy calls for the prevention of new infections through the universal implementation of the hepatitis B birth dose vaccine. It also calls for full vaccine coverage, and access to affordable diagnostics to identify and care for infected individuals.
This is the first global health sector strategy on viral hepatitis, a strategy that contributes to the achievement of the 2030 Agenda for Sustainable Development.
It covers the first six years of the post-2015 health agenda, 2016–2021, building on the Prevention and Control of Viral Hepatitis Infection: Framework for Global Action, and on two resolutions on viral hepatitis adopted by the World Health Assembly in 2010 and in 2014.
The strategy addresses all five hepatitis viruses (hepatitis A, B, C, D and E), with a particular focus on hepatitis B and C, owing to the relative public health burden they represent.
Hepatitis refers to the inflammation of the liver and is commonly caused by viral infections. It is a major global public health problem, accounting for more than 1.4 million deaths every year. It can also be caused by medications, substance abuse, toxins, alcohol and autoimmune conditions.
There are different strains of the virus, causing hepatitis A, B, C, D, and E. Of major concern in sub-Saharan Africa is hepatitis B. With a prevalence of 6.1%, it is more common in the region than HIV, which stands at the prevalence of 4.9%. In the WHO African region, mother-to-child transmission and horizontal transmission during early childhood are the leading causes of hepatitis B infection.
Early protection is vital
Women who have hepatitis B are more than 10 times more likely to pass on the infection to their newborns. The risk of becoming a chronic carrier of hepatitis B stands at 95% for infections acquired during the perinatal period.
The current WHO strategy to end mother-to-child transmission of hepatitis B includes a routine screening of all pregnant women, the treatment of highly infectious infected mothers, birth dose vaccination and the administration of hepatitis B immunoglobulin for exposed infants.
Infant vaccination has been shown to reduce the risk of developing hepatitis B by more than three times. This is particularly the case if the vaccine is administered within the first three days after birth.
But none of these practices are rigorously enforced in many parts of Africa. This is because of the absence of evidence-based policies.
A major challenge in the control of hepatitis globally is the limited attention that it has received in the past from governments and funding agencies. This is largely due to the difficulty in the attribution of death as a result of infections.
A recurring question about viral hepatitis is why it receives so little funding and attention from global health policymakers and donors. For example, the Sustainable Development Goals have a goal to “end the epidemics of” HIV, tuberculosis, and malaria by 2030 while only “combating” hepatitis, despite the fact that hepatitis accounts for more deaths than each of those infections individually1, 2.
One reason for this is the difficulty in accurately quantifying and explaining the morbidity and mortality related to viral hepatitis. This difficulty stems from the fact that hepatitis deaths are caused by five distinct viruses (hepatitis A–E) with different routes of transmission, that death occurs decades after infection, and that when people die with hepatitis-related liver cancer and cirrhosis, these deaths are not always linked to the underlying infection3.
In The Lancet, Jeffrey Stanaway and colleagues4 have made a major advance in addressing these challenges. Using the Global Burden of Disease (GBD) Study approach, which estimates the causes of mortality and morbidity and their relative importance, they have assessed the burden of disease caused by viral hepatitis from 1990 to 2013 at the country, regional, and global levels.
The main conclusion from their analysis is that viral hepatitis accounted for 1.45 million deaths (95% uncertainty interval [UI] 1.38–1.54) in 2013, a 63% (95% UI 52–75) increase compared with the 0.89 million deaths in 1990. Morbidity also increased in terms of years lived with disability (from 0.65 million to 0.87 million and disability-adjusted life-years (DALYs; from 31.7 million to 42.5 million.
The biggest increase was noted for hepatitis C infection, for which the rate of DALYs increased by 43%. Most of the morbidity and mortality is caused by hepatitis B and C infections (96% of mortality and 91% of DALYs in 2013), because these two viruses cause chronic, life-long infections, resulting in progressive liver damage that leads to cirrhosis and hepatocellular carcinoma. Finally, the burden of disease was not equally distributed worldwide.
High mortality rates in Oceania, Africa and Asia
Hepatitis-related mortality was highest (≥33.50 deaths per 100 000 population per year) in Oceania, western Sub-Saharan Africa, and central Asia. However, in absolute numbers, east Asia and south Asia have the greatest number of hepatitis deaths (52% of the total number of deaths). Unlike HIV, which primarily occurs in low-income countries (mostly in Africa), 58% of hepatitis deaths occurred in upper-middle-income countries and high-income countries.
This work is an extension of an earlier global analysis of the GBD Study2 that for the first time combined deaths due to acute and chronic infection to provide an improved estimation of the true burden of viral hepatitis.
Both Stanaway and colleagues’ study4 and the earlier analysis2 used complex statistical methods that rely on several assumptions and on estimations of the incidence and prevalence of hepatitis infection, as well as the number of deaths recorded by death certification. Unfortunately, these measures are particularly weak for hepatitis, with widely varying estimates for the number of people living with hepatitis infection and documented under-reporting of deaths due to hepatitis-related cirrhosis and liver cancer3, 5.
Stanaway and colleagues’ study4 has several important implications. It provides convincing evidence that viral hepatitis is a major contributor to the global disease burden and shows that this disease requires a stronger national and international response. Such an effective response needs to combine interventions that prevent new infections (for example, immunization, safe health care, and harm reduction) and scaling up of testing and treatment to reduce mortality among the estimated 400 million people with chronic hepatitis B and C infection.
Addressing the global burden of hepatitis infection will require substantial additional resources. Since most of the hepatitis burden is in high-income countries and upper-middle-income countries that do not receive development assistance, in many countries, these resources will probably need to come from national health budgets. For low-income countries and lower-middle-income countries, it is hoped that the improved understanding of the high burden of hepatitis will lead to an increase in international development assistance.
There are indications that the momentum is building to better address viral hepatitis. Several countries – such as Egypt, Georgia, and Mongolia – have adopted elimination goals, and in May 2016, WHO adopted the first-ever global hepatitis strategy with a goal to eliminate viral hepatitis as a public health threat by 2030, defined as a reduction in incidence by 90% and mortality by 65%6.
Global estimates documenting the high level of hepatitis-related mortality were key in advocating for the global strategy and are now further supported by Stanaway and colleagues’ findings4. Improved national estimates are now needed to monitor the success of this strategy.
The complications that can result from hepatitis, such as liver cancer, generally get highlighted as a standalone cause of death. Hepatitis is not noted as the reason for death. As a result, more money has been invested in other areas of public health, such as HIV/AIDS and tuberculosis control. This is despite deaths due to hepatitis being more numerous than those caused by HIV/AIDS and comparable to those caused by tuberculosis in the world and in Sub-Saharan Africa in particular.
Last year, as many as 325 million people around the world are affected by the global epidemic of hepatitis B and C – more than ten times the 36.7 million people who are living with HIV. (1)
Sub-Saharan Africa has one of the highest burdens of disease with over 60 million living with chronic hepatitis B, 4.8 million of whom are children younger than five years old. The regional prevalence of hepatitis B (HBV) infection is about 6.1%, with approximately one in every 15 people (1:15) infected. Additionally, there are 10 million living with chronic hepatitis C infection (HCV), with a prevalence of less than 1% infected (i.e. one person in every 100).
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