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.
ليست هناك تعليقات:
إرسال تعليق