LIVER DISEASE: LOOKING AFTER YOUR LIVER

Video transcript:
Fibrosis
So if we start with a healthy liver and injury it in some way, the liver will respond to
that injury and try and repair it. This leads to scarring or fibrosis, which will resolve if
the injury goes away. For example, if an infections is cleared. But if the injury
persists, maybe in an inherited autoimmune condition, chronic fibrosis can persist
until cirrhosis develops. And this can take up to 50 years in some people.

Now, whatever the cause of that causes injury, be it toxic damage to hepatocytes or
an autoimmune attack on biliary cells, these damaged cells will release chemical
signals. These signals will activate the stellate cells, which change their nature and
start to divide and grow, and they produce the scar tissue. Now when the balance of
scar tissue production and its normal breakdown is upset in this way, chronic
disease develops ultimately leading to cirrhosis.
Well, liver fibrosis is a process whereby the liver becomes damaged. Now that can
either be very quickly or it can be over a long period of time. And the liver's response
to damage is to produce scar tissue. And it's very like the scar tissue that you might
see on someone's skin after a bad cut or after a burn. It's hard and it's thick and it
actually has no function. So, the liver starts to get replaced by thick scar tissue that
doesn't actually work like liver anymore.
So in the beginning, scarring or fibrosis is something that the patient would have no
symptoms from. And that's one the problems with liver disease, is that you often
have no symptoms in the early stages of disease. As that scar tissue builds up, that's
at the expense of useful cells like hepatocytes that function to do all the things that
liver requires. And so, you actually find that you have lots of scar tissue and fewer

functioning cells. And you start to find the liver begins to stop working.
So fibrosis is scarring. That's exactly what it means. But there are stages. And you
might have a stage where there's just a little bit of scar tissue, and that wouldn't be a
problem. But you can have a stage where there's so much scar tissue that the liver
actually begins to lose its function.
So cirrhosis is the end stage of that. Now, cirrhosis is just a descriptive term. And so
if you said to someone in the public, "What is cirrhosis?", they say, well cirrhosis is
what you get when you drink too much. But that's not necessarily true because
cirrhosis is what happens whichever liver injury you get. And it's kind of the endpoint
that all liver diseases reach.
And it's just a description of a stage of scarring, or fibrosis, that is so extensive that it
changes the architecture, or the map, of how the liver looks underneath a
microscope. And in its more advanced phases, cirrhosis is associated with this loss
of function. Mainly because you lose all of the useful working liver cells because
they're replaced by scar tissue or isolated by the scar tissue into little islands.
There are several stages to the fibrotic process. Doctor Holt mentioned architectural
disruption of the liver in cirrhosis in the previous video. The image below builds on an
example of the lobular organisation of liver tissue, which we used our Meet the Cells
of the liver activity. We have shown the scar tissue in red in the illustration below.
The first signs of mild fibrosis are evident when fibrous expansions are observed in
the portal areas of the liver. Persistent damage can increase scar tissue deposits,
which may join up between hexagonal liver lobules, forming bridges.
Severe disease is seen when lots of bridges start to cause destruction of liver
lobules. During cirrhosis, the hexagonal lobular structures are disrupted by excessive
scar tissue, that separates hepatocytes into isolated islands. A pathologist would
examine biopsy specimens and grade the quantity and location of fibrosis to come
up with a score for a patient with liver disease. F0 represents no fibrosis, whilst F4 is
cirrhosis.
Cirrhosis has dramatic effects in the body. Development of advanced cirrhosis has
consequences for many organs and systems other than the liver, itself. The built up
of scar tissue makes it hard for blood to get into the liver and the pressure builds up.
Similar to your home plumbing, increased resistance to flow leads to the
development of back pressure, which alters the behaviour of veins in your abdomen.
This can lead to the development of varices-- which are like varicose veins-- damage
to other organs like your kidneys, and increased leakage of fluid into your abdomen
which is causing ascites. All of these complications can be life-threatening.
Researchers are working hard to pursue multiple targets that may help patients with
fibrotic livers. The primary target are hepatic stellate cells that produce fibrous
deposits. Drugs can be potentially formulated to eliminate stellate cells, prevent their
activation, or reverse it. Another valuable intervention would be to develop
therapeutic agents that can break down scar tissue or stop it from forming.

As secondary targets, scientists are looking to inhibit the accumulation of immune

cells in the liver during inflammation, as these cells can activate stellate cells and
cause scar tissue formation. The blue circles show examples of drugs and their
mode of action. If you would like to know more, please have a look at the weblink's
further use of resources and the review we supplied in PDF.