Hepatitis is an inflammatory disease affecting the liver. The disease is either caused by a viral infection, excessive consumption of alcohol, or an autoimmune disorder.  Chronic hepatitis can cause long-term liver damage and liver cancer. There are five different types of viruses that cause hepatitis: Hepatitis A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV). Each of these viruses is transmitted in different ways.

According to the World Health Organisation (WHO), approximately 1.3 million people have died from HBV and HCV, with 304 million people living with chronic HBV and HCV as of 2022. This highlights the urgent need for the development of efficient testing and vaccine programs to catch the virus early and provide treatment to prevent its spread.

The theme for this year’s is: Take Action. Test, treat, vaccinate. In this article, we explore the different types of hepatitis transmission, vaccines for hepatitis, and the current research on developing a vaccine against HCV. We will also look at the current state of testing and screening in some countries around the world.

Transmission of hepatitis

As mentioned, the different types of hepatitis viruses are transmitted in different ways. HAV and HEV are transmitted via the fecal-oral route and infection usually occurs through the consumption of food or water where the virus is present. This mostly occurs in countries where sanitization is poor. HCV is a bloodborne virus and is transmitted through the blood of an infected person. This means that the virus can be commonly spread through needles that haven’t been sterilized, or receiving blood that has not been screened properly. It can also be spread from infected mothers to babies.

Similarly, HBV is also spread through blood but is also present in semen and other body fluids. Therefore, the virus is either spread through sharing unclean needles, sexually transmitted, spread from pregnant mothers to their babies, or from child to child.

Infection of HDV can only occur when the person is already infected with the HBV virus. Therefore, vaccines against HBV are the only way to prevent HDV infection. The co-infection of both HBV and HDV, however, can be more detrimental than the infection of HDV alone. Like HAV, HEV is also spread in areas with poor sanitization and is present in low- and middle-income countries. These are places in which access to clean water and health services is limited.

Vaccines against hepatitis

There are currently vaccines against 3 types of hepatitis: HAV, HBV, and HEV. The USA’s Centre for Disease Control and Prevention (CDC) recommends the HBV vaccine be given to infants shortly after they are born. Similarly, the UK’s National Health Service (NHS) provides the HBV vaccine to babies as part of the national vaccination program, as well as adults who are not already vaccinated against the virus.

The HAV vaccine, however, is usually only taken under specific criteria. Importantly, this includes if a person is traveling to countries where HAV is prevalent, like in parts of Africa and Asia and Central and South America. Instilling efficient sanitization is essential to reduce the spread of HAV. This remains difficult in poorer, developing countries that struggle economically. In the case of protecting against HEV, a vaccine that is currently approved for human use is the HEV 239 Hecolin vaccine. However, it is not available worldwide and is only licensed for use in China.

The health burden of HCV infection is undeniable, with over 1.5 million new infections occurring each year and 75% with the possibility of resulting in chronic hepatitis.

Vaccinations are the best way to protect the population against the spread of disease. Hepatitis vaccines have been instrumental in protecting populations from viral-induced hepatitis. However, there is still a need for the development of vaccines against HCV.

Development of an HCV vaccine

The health burden of HCV infection is undeniable, with over 1.5 million new infections occurring each year and 75% with a possibility of resulting in chronic hepatitis. Chronic infection increases the potential of developing liver cirrhosis and liver cancer. There are currently only anti-viral medications developed for HCV, called direct acting-antivirals, or DAAs. These are very efficient in eliminating HCV in the infected person, but are not protective against the disease and are not always accessible to everyone.

HCV is highly variable, making it difficult to develop a vaccine against the virus. The rapid accumulation of viral mutations means that new vaccines need to constantly be designed to trigger the same immune response as the newly mutated virus. To bypass this issue, a consistent viral component needs to be identified. This means that even if the HCV virus mutates, the body’s immune response can still recognize the virus and quickly mount an immune response.

E1 & E2 glycoproteins as a vaccine target

E1 and E2 are key glycoproteins that are present on the surface of HCVs and have been extensively analyzed as a potential target for vaccines. These surface structures enable the virus to bind and enter the target cell. However, they have very diverse sequences, making it difficult to develop a vaccine that targets them. Despite this challenge, targeting these components has shown to be effective in clearing the virus by inducing the production of neutralizing antibodies.

Research shows specific regions within E1 and E2 glycoproteins that are highly conserved and that these regions are associated with viral clearance when incorporated into a vaccine.

A review published in the Open Access journal Viruses explores the HCV E1 and E2 proteins and their implications for vaccine development. The review explores the up-to-date research on the proteins and different vaccine compositions that may serve as effective protective treatments.

Research shows that there are specific regions within the E1 and E2 glycoproteins that are highly conserved and that some of these regions are associated with viral clearance when incorporated in a vaccine. The impressive discovery of the different nanostructures within the proteins was achieved through the use of cryogenic electron microscopy, or cryo-EM.

This revolutionary biological technique uses the process of flash-freezing biological specimens to cryogenic temperatures (-130 degrees Fahrenheit or less). Doing this results in obtaining a 3D image at an almost atomical resolution of the molecule. The technique has been essential in gaining knowledge of molecular structures and subsequent vaccine or drug development. The review explains how these structures will be key in developing a ‘structure-based vaccine design of an E1E2-based HCV vaccine’.

Eliminating hepatitis

A review published in the Open Access journal Pathogens on HCV vaccine development discusses how governments are key in the development of an HCV vaccine. This involves ensuring that there is a collaboration between government bodies with global vaccine initiatives, such as those led by the WHO. This would involve the development of efficient strategies and regulations to facilitate vaccine development advancement, as well as increasing their availability, safety, and efficacy.

Importantly, this incorporates efficient tests and screening programs for the public.

Importance of screening

For most diseases, testing and screening programs are a key method of reducing the frequency of disease in the population. This is also essential to stop the spread of infection with global efforts being made to reduce the frequency of disease. The WHO sets a target of eliminating hepatitis through the implementation of vaccination programs, efficient testing, and ensuring the right antiviral medicines are given as early as possible to those infected with HCV.

International and national efforts need to be made to comply with WHO guidelines so that we can work towards the goal of eliminating hepatitis.

Screening for HCV in Italy

A 2024 review published by Stasi et al. in the Open Access journal  Livers explores the current state of HCV screening programs in Italy. The authors mention how Italy has one of the highest percentages of HCV-related deaths in Europe, which is not in line with the targets expected by the WHO HCV elimination.

Considering there are currently no approved vaccines to protect against HCV, reducing the spread through implementing screening strategies remains of utmost importance. The authors of the review state that 4,707 patients in the Tuscany region who had chronic HCV infection were not treated with any type of anti-viral medication. Therefore, identifying individuals who have already been afflicted requires a strategy.

This initiated the launch of a program by the Tuscany Regional Authority which aimed to eradicate HCV in the region of Tuscany. As part of the strategy, targeted information programs were carried out, and health authorities put in place a call-to-action campaign for people who had previously been diagnosed with HCV but had not received DAA treatment. Most importantly, free screening was established for the population which is essential for monitoring and reducing the spread of the virus. They conclude how national as well as international collaborations are needed to overcome barriers that are still present even in high- and middle-income countries, such as Italy.

Screening in the UK and USA

Meanwhile, in the USA, laboratory tests screening for HBV are available for anyone 18 years or older. The data show that 880,000 people were living with chronic HBV from 2013 to 2018. The Hepatitis B  Foundation states that, in the USA, up to 24 million people are chronically infected but only 25% are aware they are infected. The CDC has published extensive guidelines and recommendations for a strategy to increase screening among adults and to minimize the stigma that may be associated with the tests.

In the UK, screening for HBV is recommended. According to data from 2021, around 206,000 people were living with chronic HBC infection, and 92,900 living with HCV infection. The tests are available for free at sexual health clinics and are encouraged for those who are more at risk of acquiring infection. As pregnant women have from 90 to 96% chance of transmitting HBV to the child, the test is also recommended during pregnancy.

Future work

There is still a lot to be done considering the barriers surrounding vaccine development and global screening. International and national efforts need to be made to comply with the WHO guidelines so that we can work towards the goal of eliminating hepatitis. Key aspects of this include research on vaccine development for HCV as a protective treatment against infection. It also includes research and collaboration with governments to implement public information campaigns and programs to boost testing and screening.

MDPI publishes Open Access research on hepatitis. To read more, you can see MDPI’s full list of journals which cover subjects including virology, vaccines, health policy and public health.