The Australia Antigen

I feel a little left out some times on the internet as many (but certainly not all) of my bloggy friends are English or American. So, just to fill you in, the 26^th of January is Australia Day and it commemorates the landing of our first fleet in 1788 and the planting of the British flag in what was then known as New Holland and is now known as Sydney Cove, New South Wales, Australia. Most people celebrate the day with a public holiday, a beer or two, a barbi and the TripleJ Hottest 100.

We will get back to the Australiana theme in a moment but I want to take it down a notch first by talking about Hepatitis B virus.

Hepatitis diseases are not limited to those induce by viruses. In fact hepatitis just means inflammation of the liver from hepat(o)- for liver and –it is meaning inflammation of. This has led to the common misconception that the Hepatitis viruses (A, B, C, D, E) are related to each other, they’re not, but they do all cause liver inflammation. In fact according to the Balitmore Classification of viruses they fall in completely different families. Furthermore the run of letters, which also suggest relatedness, simply describe the order in which the viruses were identified.

The Baltimore Classification describes the lifecycle of all viruses based on their genome structure. Protein is produced based on the mRNA sequence so that’s why all lines flow back to mRNA.

While all are problematic in their own way for this post we are interested only in Hepatitis B virus (HBV), arguably the biggest problem in the (not) family of hepatitis inducing viruses.

How big a problem is HBV? Well, approximately 2 billion people worldwide are infected, greater than 350 million people are in the chronic phase of infection and its estimated that a quarter of these people will die of liver cancer or other complications directly caused by HBV.

Like many viruses encased in a membrane (a so called enveloped virus), HBV requires body liquid exchanges to transmit from person to person but is not necessarily picky as to which liquid and transmission has been observed by blood exchange, sexual contact and even maternal-foetal exchange across the placenta.

HBV disease is very well characterised and follows a fairly generalised route. Following transmission the viruses work their way into the blood stream and eventually find their way into the liver where they can attach and enter liver cells. Once inside the cells the virus and its components are very stable and viral replication kicks in resulting in huge numbers of virus being produced and seeking out new liver cells. This infection stage can last up to 6 months with almost no symptoms beyond generalised flu-like symptoms or a touch of jaundice.

Following initial viral replication there are three outcomes are possible. Best case scenario, you mount an early, strong and effective immune response that removes all the virus from your system. Worst case scenario #1 (short term), you develop a form of acute hepatitis called fulminant hepatitis which is caused by your immune system reacting too strongly and liquifiying your liver in an attempt to remove the virus resulting in a quick death. Worst case scenario #2 (long term), your immune response is slow or weak and the virus persists resulting in a chronic infection. An interesting little side note here is that if you are a child your chances of developing chronic hepatitis B skyrocket to 95% compared to the 5% chance to adults and at this stage we really don’t understand why.

So your either fine, dead or a time bomb and chronic sufferers can look forward to a life of medications attempting to prevent death. Having said that some chronic HBV patients go on and live lives free of complication or further symptoms but most end up with either a passive or active form of liver destruction depending on whether you show any symptoms or not respectively.

The destruction of the liver is immune mediated which mean the virus doesn’t actually kill liver cells but its presence activates the immune system inducing it to kill any cell with virus. As the liver can regrow your left with constant cell death and constant cell renewal but it all comes at a cost, scars. Scars in tissues are called scar tissue (duh) or more accurately fibroma. Fibromas are a problem as they impair organ function and when you develop too many the organ starts to die as blood cannot flow to all parts of the liver or promotes the liver to overcompensate and regenerate faster leading to cancer – hepatocellular carcinoma.

Pic courtesy of my good friend Thomas Tu from the wonderful blog Disease of the Week. In unvaccinated hosts this is the pathway through HBV infection.

So what can we do about HBV? Currently your best option is vaccination. Its pretty cheap (for me it was any way), very safe and really effective. As well as being the best option, its kind of the only option as all the anti-viral drugs currently available do not ‘cure’ the virus, they can only act to freeze or pause it. When you stop the drugs the virus un-pauses. As I will most definitely talk about at a later date vaccines are awesome, but at least for HBV they might not be the golden bullet they can be for other disease. Vertical transmission, mother to child, in the womb is impossible at this stage to prevent as you just cant vaccinate an embryo but effective vaccination of everyone else will prevent horizontal transmission between all other people.

So I started this with an Australian flavour and that is because I came across some terminology I have never heard before. It turns out the antigen that I've always called HBsAg (Hepatitis B surface antigen) was originally isolated from an Australian aborigine and so was commonly referred to as the Australia antigen. Whilst we do not call it that anymore this antigen is very important as it is used in current vaccines designed to prevent virus entry into cells.

So after a very long and round-about trip from Australia Day to HBV and (kind of back again) I wish you a very happy Aussie Day and encourage you to fulfil all the best Aussie stereotypes. Wear a cork hat (only found in souvenir shops), a blue singlet and very short shorts (only seen on 'Australian in movies'), drink a big Fosters (nobody drinks that rubbish here) and ride around on a kangaroo (one of natures truly most terrifying animals if you ask me). G’Day mates!

See those muscles, remember, he hops on his back legs…

EDIT - 27/1/11 - The very clever Thomas Tu who gave me on of the pics in this article, writes at the stupendous Disease of the Week! and is a HepB researcher has informed me that he thought my wording was a little sloppy. HepB doesn't really get transmitted vertically from mother to child as it is not passed across the placenta. Technically its still horizontal as the virus is passed in the fluids during birth. My point about vaccination in utero still stands but Thomas is right. Lets call is diagonal transmission and be done with it :)

References

Blumberg, B. (1984). Landmark article Feb 15, 1965: A "new" antigen in leukemia sera. By Baruch S. Blumberg, Harvey J. Alter, and Sam Visnich JAMA: The Journal of the American Medical Association, 252 (2), 252-257 DOI: 10.1001/jama.252.2.252
Lee WM (1997). Hepatitis B virus infection. The New England journal of medicine, 337 (24), 1733-45 PMID: 9392700