Tag: hepatitis B

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Interventions to Eliminate Vertical Transmission of Hepatitis B in Africa

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Photo by William Fortunato on Pexels

Researchers at the University of Liverpool have conducted a large-scale analysis that sheds light on the critical steps needed to combat the vertical transmission of chronic hepatitis B virus (HBV) in Africa.

Almost two thirds of all new hepatitis B infections globally occur in Africa. The newly published paper in The Lancet Global Health shows the importance of giving the hepatitis B birth dose vaccine (HepB-BD) within 24 hours of birth, and the potential impact of providing antiviral therapy (antiviral prophylaxis) to mothers during pregnancy. The study estimates for the first time that hepatitis B vertical transmission (passed from mother to baby) could be eliminated in Africa, with increased coverage of these two key interventions.

Chronic hepatitis B is the leading cause of liver cancer and liver cirrhosis in Africa and deaths are rising. Most cases of liver cancer are diagnosed late and are associated with a very poor prognosis in the region. Vertical transmission is one of the commonest routes of infection and is associated with an increased lifetime risk of severe liver disease.

Dr Alexander Stockdale, Senior Clinical Lecturer at the University’s Department of Clinical Infection, Microbiology and Immunology, based at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme, together with Dr Nicholas Riches at Liverpool School of Tropical Medicine, led the comprehensive analysis of more than 113 individual studies which reported on the prevalence of hepatitis B in more than 190 000 women and investigated rates of vertical transmission.

The World Health Organization (WHO) African region faces a significant burden, accounting for 63% of the global total of new infections. This amounted to 771 000 new infections and 272 000 deaths in 2022. Among children under 5 years, the prevalence of HBV stands at 2.5% in the WHO African region – the highest globally.

Dr Alexander Stockdale said: “This study makes the case for investment in birth dose vaccination and maternal antiviral prophylaxis, in view of the exciting potential for elimination of vertical transmission in the WHO African region in our lifetime. Vertical transmission is a key route of new hepatitis B infections. Due to limited implementation of interventions, elimination targets are not currently being met. We project that expanding HepB-BD vaccination coverage to 90% could reduce transmission events by 44%, and adding maternal antiviral prophylaxis for 90% of eligible women could further reduce transmission by 86% and achieve the WHO targets for elimination.”

Dr Stockdale and colleagues have also recently been awarded £3million funding from the National Institute of Health and Care Research to conduct implementation research in Malawi and The Gambia. The NIHR Global Health Research Grant will allow researchers in Malawi, led by Dr Stockdale and in The Gambia, led by Professor Maud Lemoine and Dr Gibril Ndow, to evaluate the effectiveness, safety, feasibility and cost-effectiveness of giving antiviral treatment (tenofovir) to all pregnant women living with chronic hepatitis B to prevent transmission. This study will provide vital evidence on the potential impact of this strategy to guide public health policy in Africa, which has been recognised as a key knowledge gap by the WHO in the 2024 hepatitis B guidelines.

Source: University of Liverpool

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Why are Humans Susceptible to Hepatitis B Virus – But not Monkeys?

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Photo by Andre Mouton on Unsplash

Hepatitis B virus (HBV) infection is a leading cause of chronic liver diseases, that spreads among individuals through blood or body fluids. According to the World Health Organization, globally 1.2 million new HBV infections are reported every year – most in low- and middle-income countries. HBV infections are limited to a few species, including humans and chimpanzees. Despite their close evolutionary relationship with these animals, old-world monkeys are not susceptible to HBV infections.

In a new study published in Nature Communications, scientists led by Visiting Professor Koichi Watashi from the Tokyo University of Science to uncover why monkeys are naturally resistant to HBV infection.

Using cryo-electron microscopy, scientists solved the structure of a membrane receptor found in liver cells called the sodium taurocholate co-transporting polypeptide (NTCP) in macaques. HBV binds to human NTCP using its preS1 region in the surface protein. Prof Watashi explains, “We identified a binding mode for NTCP-preS1 where two functional sites are involved in human NTCP (hNTCP). In contrast, macaque NTCP (mNTCP) loses both binding functions due to steric hindrance and instability in the preS1 binding state.”

To understand this ‘interspecies barrier’ against viral transmission, Prof Watashi and his team compared the structures of hNTCP and mNTCP, identifying differences in amino acid residues critical for HBV binding and entry into liver cells. hNTCP and mNTCP share 96% amino acid homology, with 14 amino acids distinct between the two receptors. A key distinction among these differences is the bulky side chain of arginine at position 158 in mNTCP, which prevents deep preS1 insertion into the NTCP bile acid pocket. For successful viral entry into liver cells, a smaller amino acid like glycine, as found in hNTCP, is necessary.

Interestingly, the substitution of Glycine by Arginine in mNTCP was at a position far away from the binding site for bile acid. Prof Watashi adds, “These animals probably evolved to acquire escape mechanisms from HBV infections without altering their bile acid transport capacity. Consistently, phylogenetic analysis showed strong positive selection at position 158 of NTCP, probably due to pressure from HBV. Such molecular evolution driven to escape virus infection has been reported for other virus receptors.” Further lab experiments and simulations revealed that an amino acid at position 86 is also critical for stabilising NTCP’s bound state with HBV’s preS1 domain. Non-susceptible species lack lysine at this position, which has a large side chain; macaques instead have asparagine, which contributes to HBV resistance.

The researchers also noted that bile acids and HBV’s preS1 competed to bind to NTCP, where the long tail-chain structure of the bile acid inhibited the binding of preS1. Commenting on these findings, Prof Watashi stated, “Bile acids with long conjugated chains exhibited anti-HBV potency. Development of bile acid-based anti-HBV compounds is underway and our results will be useful for the design of such anti-HBV entry inhibitors.”

By unravelling the structure of mNTCP and pinpointing the amino acids that facilitate viral entry into liver cells, researchers have opened the door to new therapeutic avenues. Furthermore, the implications extend beyond HBV, offering critical insights into other viruses, including SARS-CoV-2, and their potential to cross species barriers. This research not only enhances our understanding of viral dynamics but also serves as a crucial tool in the ongoing quest to predict and prevent future pandemics.

The future of global health hinges on these revelations, promising a path toward more equitable access to treatments and a stronger defence against emerging viral threats.

Source: Tokyo University of Science

Categories : VaccinesTags :

Hepatitis B Vaccine at Birth can Save Thousands of Lives

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By Daniel Steyn for GroundUp

The hepatitis B virus is estimated to cause about 820 000 deaths a year globally. It is one of the leading causes of liver cancer. One in 20 people in South Africa is infected with hepatitis B, yet few people know about or have been tested for the virus.

During a media briefing on Friday, organised by the Gastroenterology and Hepatology Association of Sub-Saharan Africa (GHASSA), a panel of experts stressed the need for urgent interventions to eliminate hepatitis.

There are clear solutions, the experts said: increase awareness, increase access to testing, and prevent childhood transmission through birth-dose vaccination and screening and treating pregnant women.

“We are way overdue on bringing hepatitis out of the shadows and into the light,” said Professor Mark Sonderup, from the University of Cape Town’s (UCT) academic hospital at Groote Schuur.

In South Africa, an estimated 2.8 million people have chronic hepatitis B. Liver cancer caused by hepatitis B is on the increase in Africa and worldwide. Besides cancer, the virus can cause serious liver disease.

Hepatitis B is transmitted through bodily fluids, including semen and blood. Antiretroviral treatment for chronic hepatitis B is available but only 22% of cases are diagnosed.

An estimated 76 000 children in South Africa under the age of five have hepatitis B. Children infected with hepatitis B are more likely to develop a chronic infection.

Children infect each other: the virus multiplies in the body without presenting symptoms and a drop of blood shared through play between children can transfer the virus.

“They walk around like ticking timebombs, spreading infections,” said Dr Neliswa Gogela, liver disease specialist at Groote Schuur. Hepatitis B is 100 times more infectious than HIV, said Gogela.

Children born in South Africa receive a hepatitis B vaccine at six, ten, and 14 weeks old. If a vaccine dose was given at birth, it would cut out the first six weeks during which a child could become infected. Birth-dose vaccines are government policy but it has not yet been implemented. Other African countries like Namibia have introduced birth-dose vaccines.

The virus can also be transmitted from mother to child during and after birth. Pregnant women should be screened as part of prenatal and antenatal healthcare services, said Professor Wendy Spearman, head of Hepatology at UCT. Those eligible for treatment should receive antiretrovirals to prevent transmission of the virus to the child.

Hepatitis B is a silent killer, said Professor Mashiko Sechedi, head of gastroenterology at Groote Schuur. The virus stays in the body and only presents symptoms when the disease is at an advanced stage. It can cause multifocal liver cancer which renders the liver inoperable. “In South Africa, we’re seeing young patients presenting with advanced disease,” said Sechedi.

Professor Eduard Jonas, a surgeon at Groote Schuur, said that half of the patients in Sub-Saharan Africa who are diagnosed with liver cancer die within two and a half months of diagnosis. Late diagnosis and lack of treatment capacity make liver cancer particularly deadly in Southern Africa, he said.

Screening and testing for hepatitis are not easily accessible, said Professor Geoff Dusheiko, from Kings College in London. Whereas anyone wanting to do an HIV test can go to any government clinic and receive a point-of-care rapid test, they cannot do so for hepatitis B.

Rapid tests for hepatitis B are available but have not been rolled out by the government, so the only way to do a hepatitis test through public health facilities is to take blood, which is sent to a laboratory for testing.

While HIV, malaria and TB have attracted significant attention and funding, hepatitis has not. “We need people living with hepatitis B demanding access to treatment,” said Spearman.

Republished from GroundUp under a Creative Commons Licence.

Source: GroundUp