so what is autoimmune liver disease, and what are the symptoms? Well they’re are a family of relatively rare liver diseases. Around– if we say 100 people with liver disease, around five of them will have an autoimmune liver disease. And by that we mean it’s a liver disease where their body attacks either their liver cells or their bile ducts. We like to think of them as a family of diseases, because they seem to be related, and often have symptoms and signs that are shared.
And the three diseases that we see as part of this family are autoimmune hepatitis– which we think of nestling in the middle of the family where the liver cells are inflamed and attacked by the immune system. And then there are two autoimmune bile duct diseases. The more common one is primary biliary cirrhosis, and that’s a disease that one in the 1,000 women over the age of 40 have. And that’s an immune attack on the small bile ducts, the so-called lymphocytic cholangitis. And then the rarer, large bile duct autoimmune disease is a disease that we give the name primary sclerosing cholangitis, and that’s a disease where there is fibrosis and sclerosis of the large bile ducts.
And very commonly, those patients also have inflammation in their bowel, inflammatory bowel disease. Many patients actually have no symptoms of these diseases, but when they do have symptoms, they’re often fatigued, and sometimes they itch. And quite commonly, they are identified when they go to their doctors for either abdominal pain or routine testing, and their liver enzymes are high. And as a result, when we’ve excluded more common liver diseases, like alcohol and viruses, we start to think about the autoimmune liver disease family, and that’s when we try and make a diagnosis for them. Right, so who can get autoimmune liver disease? So, I mean these three diseases are actually seen in all ages, and in both men and women.
So classically, primary biliary cirrhosis, that’s the small bile duct disease which is autoimmune, is seen in middle aged women in their 50s, and around 90% to 95% of patients are women. Primary sclerosing cholangitis is different. It can be seen in all ages, but the common age of presentation is between the age of 30 to 40. And it’s slightly more common in men. And as I said, the majority of patients, particularly if they’re white, will have inflammatory bowel disease. Autoimmune hepatitis can also be seen in all ages, so we have children with autoimmune hepatitis, and we have very elderly people with autoimmune hepatitis. But generally, people imagine that it’s a slightly more common disease in younger women.
Although, actually as we learn more about the disease and test more for it, we actually see it in all ages in both men and women. Probably about equal instance. Do we know what causes autoimmune liver disease? Well that’s the million dollar question. The answer is no. What we do know for sure is that autoimmune liver disease must occur for two reasons. One is that you’re predisposed to it genetically. And by that I mean in the loosest sense, you’ve got lots of different genes that predispose you to autoimmune attack on your liver. And then secondly, there must be something in the environment that triggers it.
So when we look at the autoimmune liver diseases, we see that the patients and their families have all got other autoimmune diseases, and that sort of highlights why we think there’s a genetic association or risk for these diseases. And certainly the genetic studies that have been done in all three diseases really do confirm that there’s an association with the HLA system, which is a very important part of the immune system for presenting foreign things to the immune system, as well as other genes that are very important immune pathways. In terms of the environment, we’re quite clear that there must be environmental triggers.
And we know that, for example, we see patients with autoimmune hepatitis that follows some kind of drug injury– they take a medicine like nitrofurantonin, and they get a liver injury that looks like autoimmune hepatitis. We know that, for example, patients with PBC are more likely to be smokers, suggesting that there might be something in smoking which is an environmental trigger. As I told you, we know that patients with PSC have got inflammatory bowel disease, which makes us really wonder what’s going on in their bowel which may trigger their immune attack on their liver. So it’s a mixture of genes plus environment, and then they come together.
And then once the immune system’s out of the box, we find it hard to squidge it back in. So what should one do, if one thinks that they may have autoimmune liver disease? Well the first thing is it’s a diagnosis of exclusion. So it’s an important diagnosis to make, because it’s important for patients to be treated early. We all know that with any liver disease, it’s much better to treat the patient before they’ve got lots of scarring, before they’ve got cirrhosis. You’ve got a much better chance of reversing the damage before the damage is too significant. So patients should have their liver tests followed up.
And if there isn’t an obvious cause, such as being overweight, such as drinking too much, such as viral hepatitis B or C, then you need to seriously think about autoimmune liver disease, and they’ll go and see their gastroenterologist, or their hepatologist, who will go through a panel of tests, and particularly will look for patterns of blood tests, and patterns of immune markers that might help them. So, for example, when you’ve got a bile duct disease, your alkaline phosphatase is very high, so that’s a pattern that suggests bile duct inflammation. Whereas when you’ve got hepatitis, your AST or ALT your transaminases are very high.
So your doctor will first of all say, well is it a hepatitis or a cholestasis, a biliary problem. And then they’ll either do some scans, ultrasounds or MRIs, and some immune tests. So, for example, we know that our patients have high globulins, and so if you have PBC your immunoglobulin M component is elevated. Whereas if you’ve got autoimmune hepatitis, it tends to be your immunoglobulin G. So that’s tests that they can do. And then, because these diseases are autoimmune diseases, some of them are associated with auto antibodies. So PBC, for example, 95% of our patients have got mitochondrial antibodies in their blood. In autoimmune hepatitis, we can pick up auto antibodies.
And so what their doctor does is put everything together, make sure what isn’t there, and then tries to work out whether it’s a bile duct problem, or a liver cell problem. Sometimes the patient still needs a liver biopsy. And liver biopsies are very important, because the pathologist can look under the microscope and can look at the pattern of inflammation and where it is, and try and work out what’s caused it. But more importantly tell you how severe it is. And once this is confirmed, what can one do to treat autoimmune hepatitis? Well, of all the autoimmune liver diseases, actually autoimmune hepatitis is the one that we can treat the best, although our patients don’t particularly always like the treatment.
So for autoimmune hepatitis, that’s the most responsive to therapy, because if you give a patient steroids, you have a big impact on the immune system’s attack on the liver cells, and you can switch it off completely, actually. And you can then put the disease into remission, and you can use drugs like azathioprine or mycophenolate, which are more subtle immuno suppressants to keep the disease in remission. The autoimmune bile duct diseases are a little bit harder, actually. And they’ve been less responsive. Now, although they are autoimmune diseases, when you give drugs like steroids to patients, they don’t actually work, which is an interesting paradox.
But for PBC, the more common bile duct disease, we give a drug called ursodeoxycholic acid, and that’s a very interesting drug, because actually that’s a bile acid that you make yourself. And we all have ursodeoxycholic acid in our bile, but it’s at a low level. And we supplement that pharmacologically, we make the urso levels quite high, and it’s a more nontoxic, less detergent, bile. And that seems very helpful for patients with PBC. It’s less helpful for patients with PSC. So currently, patients with PSC don’t have any therapies, and usually try and enter clinical trials. Patients with PBC only enter a clinical trial if they didn’t respond to ursodeoxycholic acid, which is about a third of patients.
And patients with autoimmune hepatitis would like new treatments, but they are trapped by the fact that it’s quite a rare disease, which is reasonably well treated with what we’ve got. But the patients don’t like the side effects, particularly of steroids.
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