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Unlocking the power of the immune system to get ahead of hepatitis B

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22 June 2022

The liver performs over 500 tasks each day that help keep us alive and healthy and has the unique ability to regenerate itself when it becomes damaged.1 Yet some people’s livers harbour an infection that could impact liver function and may cause the organ to fail: hepatitis B.

Hepatitis B virus infection is caused by a virus that is spread through blood and bodily fluids and localises in the liver. Estimates suggest that one in every three people has been exposed to the hepatitis B virus at some point in their lives, but many of these people will develop natural immunity to the infection.2 However, up to 10% of adults and nearly all babies infected via their mother during birth will experience an inadequate immune response to the virus causing them to develop chronic, or lifelong, hepatitis B virus infection. The World Health Organization (WHO) estimates that over 296 million people live with chronic hepatitis B virus infection worldwide, making it a major global health problem.3

What is chronic hepatitis B?

Watch this animation to learn more about hepatitis B, who it affects, and how we are getting ahead of chronic hepatitis B together.

At GSK, we have been working hard to get ahead of hepatitis B for decades. Vaccines that help prevent hepatitis B virus infection now exist, and antiviral therapies are available to help control the infection. Yet the burden for many remains. We are using our expertise to advance research to help reduce this burden.

“Even when treated, chronic hepatitis B can progress to liver failure and liver cancer, which results in nearly 900,000 deaths per year.3 Current antiviral treatments for chronic hepatitis B may need to be taken for life, and regular monitoring is often required to check for any further liver problems, presenting the need for longer-lasting solutions.”

Great progress has been made in treating the virus, though more can be done

There is currently no cure for people living with chronic hepatitis B virus infection. Those unable to naturally fight off the virus may live with it for many years without experiencing any symptoms until the liver becomes damaged. Because of this, people diagnosed with chronic hepatitis B virus infection need to be regularly tested and monitored to watch out for liver damage.

Additionally, we recognise that people living with chronic hepatitis B virus infection may also endure significant psychological pain and social stigma. Although most transmission occurs from mother to child during birth, there are other routes of transmission which can cause people to view their condition as something shameful, potentially reducing their likelihood to seek care and their quality of life.4,5

Current hepatitis B treatments work to suppress the activity of the virus, keeping it inactive with antiviral therapies. These treatments can help protect the liver but rarely clear the virus completely. This means many people with hepatitis B require treatment for the rest of their lives.

To get ahead of hepatitis B, scientists are looking at innovative ways to address both the viral infection and the resulting immune dysfunction which allows the virus to persist in the body long term. With hepatitis B virus infection, the virus both embeds its DNA into our liver cells and hijacks the cell’s own processes to produce proteins for the virus.6 Current treatments seek to minimise the effects of the virus by focusing on the viral DNA replication process.

Scientists are now looking to go one step further by switching the focus to the virus’ RNA. They have discovered that interfering with the RNA not only stops viral replication but also halts the production of viral proteins and allows for an opportunity to investigate whether this can stop hepatitis B in its tracks.

Unlocking the immune system to control hepatitis B

By using investigational technologies, researchers hope to harness the power of the liver to reduce the proteins made by the virus in its effort to evade the immune system. Scientists are pursuing a new approach that recruits enzymes present in all cells to break apart hepatitis B viral RNA so that it no longer works.

One sequence of the viral RNA code can contribute to several different hepatitis B virus proteins and also to viral replication. By targeting that sequence for ‘clean out’ there is a potential broad impact on viral protein production, with the goal of eliminating the proteins’ effects on the immune system. This could set the stage for the immune system to take over and keep the virus suppressed for the long term without the need for ongoing medication.

What is functional cure for chronic hepatitis B virus infection?

Watch this animation to discover what a ‘functional cure’ means for people living with hepatitis B.

Whilst the ultimate aspiration is to find a cure for hepatitis B, this approach could lead to what is called a ‘functional cure,’ where the virus is undetectable in blood and at a low enough level in the liver that it can be controlled by the immune system without medication, meaning liver damage is less likely to progress and the burden of the disease on people will be reduced. Scientists hope this new approach will control the hepatitis B virus and lead to longer-lasting solutions for the 296 million people currently living with this disease.3

“Hepatitis B has been causing death and disability on a global scale for many years. We are committed to following the science to explore new approaches to address unmet needs and provide longer-lasting solutions for patients with this potentially life-threatening liver infection.”

References

  1. John Hopkins Medicine. Liver: Anatomy and Functions. Available online at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/liver-anatomy-and-functions. Last accessed: May 2022.
  2. World Health Organization Regional Office For Europe. Hepatitis Data and Statistics. Available online at: https://www.euro.who.int/en/health-topics/communicable-diseases/hepatitis/data-and-statistics. Las accessed: May 2022.
  3. World Health Organisation, Hepatitis B Key Facts, June 2022
  4. Le Gautier, R, Wallace, J, Richmond, JA, Pitts, M. The personal and social impact of chronic hepatitis B: A qualitative study of Vietnamese and Chinese participants in Australia. Health Soc Care Community. 2020; 00: 1– 9. https://doi.org/10.1111/hsc.13197
  5. Tu T, Block JM, Wang S, Cohen C, Douglas MW. The Lived Experience of Chronic Hepatitis B: A Broader View of Its Impacts and Why We Need a Cure. Viruses. 2020;12(5):515. Published 2020 May 7. doi:10.3390/v12050515#
  6. Delaney WE, et al. Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus. Antimicrob Agents Chemother. 2006;50(7):2471-2477. doi:10.1128/AAC.00138-06
  7. Lok, A.S., Zoulim, F., Dusheiko, G. and Ghany, M.G. (2017), Hepatitis B cure: From discovery to regulatory approval. Hepatology, 66: 1296-1313

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