The Past, Present and Future of Hepatitis B

an overview - by Maia Sissons

Maia Sissons attended “The Liver Meeting”  organised by the American Association for the Study of Liver Disease  in Boston at the beginning of November. The following article is an account of the conferences she attended, which are listed at the bottom. All information and opinions in this article were provided by the speakers.


A History of Hepatitis B

The Hepatitis B virus was discovered by Baruch Blumberg at the Fox Chase Cancer Centre in Philadelphia in 1967. Blumberg and his team were working on a wide-ranging investigation into inherited susceptibility to disease. At this time, the human genome was yet to be sequenced, but it was possible to look at variation in serum proteins. While studying the serum of people who had undergone multiple blood transfusions, Blumberg discovered the ‘Australia antigen’. He then identified this as the Hepatitis B surface antigen, or HBsAg.

On further investigation of this “new” virus, Blumberg noted that - unusually - in addition to the production of the whole virus, the liver also produced cells which were only part of the surface of the virus. These cells could be used to produce a vaccine.

Within two years of the discovery of Hepatitis B (or HBV), trials for a vaccine were underway. Blumberg had also identified a link between Hepatitis B and primary liver cancer, and he had developed a programme to screen donor blood for the virus.

Blumberg was awarded the Nobel Prize for Medicine in 1976.


Vaccination

In trials, the new vaccine was shown to be safe and effective using only a few thousand test cases (compared to more than 1.2 million used in the trials for the Polio vaccine). The vaccine has been proven to be 95% effective.

A vaccination programme commenced in the US in the early 1980s, followed by a dramatic drop in the number of HBV carriers, and a significant drop in the incidence of primary liver cancer.

In 1992, the World Health Organisation set a goal that by 1997 all countries should have integrated the HBV vaccine into their infant immunisation programmes. Despite initial support for this initiative, only 66% of member countries had complied by 2001. It is estimated that currently only 55% of infants worldwide have completed the course of the vaccine.

It is estimated that 3.5 million lives in China have already been saved as a result of vaccination, but that due to an incomplete programme of immunisation, there are 6,000 new cases in the country every 24 hours.

The UK is one of a tiny minority of countries that still does not have a universal vaccination programme for infants, although immunisation is offered to “high risk” individuals.





Hepatitis B today

Hepatitis B is “one of the most neglected pandemics in the world.” There are an estimated 350 million carriers of the Hepatitis B virus worldwide (compared to 35 million carriers of HIV). This is the equivalent of the entire population of the US and Canada, or approximately 1 in 20 of the world’s population.

It is estimated that as many as 2 in 3 people who are chronically infected are unaware that they have the virus. This means that they are unable to receive the care they need, and also that they are more likely to pass the virus on to others. Without care, around 1 in 4 of Hepatitis B carriers will die from cirrhosis or liver cancer, which has a survival rate of less than 1 in 10. It is estimated that around 1 million people every year die as a result of liver failure due to HBV. Many of these are relatively young people, who contracted the virus in infancy from an infected parent.

Even in countries where the HBV vaccine is offered at birth, such as the US, there are still significant numbers of carriers, largely due to immigration from areas where the virus is more prevalent.

A lack of understanding of how the virus is transmitted sometimes leads to discrimination, which, in turn, discourages people from being tested and even treated.


Hope for Hepatitis B

Hepatitis B, and the liver diseases associated with it are, in theory, entirely preventable.

For those who are already chronically infected, there is hope in the form of increasingly effective anti-viral drugs. Chronic HBV patients are only likely to develop liver diseases when there are high levels of the virus being produced in their liver. Anti-viral drugs can decrease the amounts of virus being replicated, and this will have a positive and long-term effect on the health of the liver.

A recent study using Entecavir, for example, has shown long-term improvements in the following ways:

    1.    Potent, long-term viral suppression - 94% of patients maintaining an undetectable viral lode after 5 years.

   2.    High genetic barrier to resistance - only 1.2% of patients developed a resistance to the drug after 6 years.

    3.    Improved liver function and reversal of liver damage - 92% of patients experienced improvement, some experienced reversal of cirrhosis.

In a recent study in Italy, a small number of patients using Entecavir began to produce their own antibodies, meaning that they were able to stop treatment completely.

While for most patients, treatment with anti-viral drugs is likely to continue throughout their lives, it has a better outcome and is significantly more cost-effective than treating progressive liver disease. In most countries, there is a desperate shortage of donor livers - the situation has been compared to “lifeboats on the Titanic.” If the anti-viral drugs that are available can simply prevent worsening of the disease, they will prevent the need for liver transplants for a great number of patients.

In order to help patients before disease progresses too far, it is vital that there is in place an effective screening and monitoring programme. If people are aware that they have Hepatitis B, the virus can be monitored and treated when appropriate.

If a universal immunisation programme were to be carried out thoroughly, there would, eventually, be no need to screen, monitor or treat Hepatitis B. In 1980, the smallpox virus was eliminated - there has not been a single case worldwide since then. Why not Hepatitis B?


Conferences

40 Years of Hepatitis B: A Retrospective
Baruch Blumberg, MD, PhD
1976 Winner of the Nobel Prize in Medicine
Fox Chase Cancer Center, Philadelphia, USA

Hepatitis B: The “Forgotten Disease”
Samuel So, MD, FACS
Director, Asian Liver Center
Director, Liver Cancer Program
Stanford University School of Medicine, USA

Combating Hepatitis B Through Public Health Initiatives
John Ward, MD
Director of Viral Hepatitis Program, US Centers for Disease Control and Prevention

Progress in Hepatitis B Treatment
Hugo Cheinquer, MD, PhD
Division of Gastroenterology and Hepatology
Universidade Federal Do Rio Grande Do Sul
Porto Alegre, Brazil

Baraclude in the Real-Life Setting
Professor Lampertico
Division of Gastroenterology
University of Milan, Italy

	New research in Entecavir	New NICE appraisal