Hello, everyone. We’re now moving on to a particularly significant liver disease, which is becoming increasingly important, internationally. So we’ve decided to move from our interview-type format and, instead, show you some key facts, in this video. We’re going to consider nonalcoholic fatty liver disease, or NAFLD, which is a condition where too much fat accumulates in your liver. Think of the fatty foie-gras livers which are eaten by some; it’s the same kind of situation. So what causes a liver to become fatty? Essentially, it’s a buildup of lipids or triglycerides in the tissue. And you’ll remember, from our earlier activities, that triglycerides can be stored in the liver and either broken down to release energy or sent into the body, for use elsewhere.
Now, alcohol consumption can increase the production of triglycerides in the liver and cause a similar fatty accumulation. But, here, we’re specifically considering disease which appears in the absence of significant drinking. So an imbalance in this normal uptake, utilisation, and release of lipids from the liver leads to the fat accumulation. So, put simply, if you put too much fat in– maybe from a poor diet, or if you don’t exercise enough and use up your calories– that fat accumulates. Insulin resistance, in conditions like diabetes, could also slow down the breakdown of fat, and some drugs like steroids and other anti-inflammatory treatments, like methotrexate and sulfasalazine, can also upset this balance.
This fat appears as little bubbles of lipid in the tissue, in the hepatocytes, and we saw this in our video with Professor Hubscher, and you can also see it in the image on the right. Now, for many years, this fat accumulation was thought to be harmless. But we now know that this can trigger the activation of both immune cells and stellate cells, which causes liver fibrosis. And patients can then progress to more severe disease, called NASH, or nonalcoholic steatohepatitis, which can lead to cirrhosis and liver failure. So who is likely to get NAFLD? Well, as you might expect, it’s closely associated with diabetes and obesity, where that balance of lipid handling is upset.
Polycystic ovary disease is also, sometimes, associated with insulin resistance. So ladies with this condition are more likely to develop fatty livers. Also, people with other components of the metabolic syndrome, such as hyperlipidemia and cardiovascular risks, such as high blood pressure, are more likely to get NAFLD. Patients taking the kind of anti-inflammatory drugs we just mentioned may also have an increased risk. And interestingly, some patients with viral hepatitis are also susceptible, as some viruses also alter the way the liver exports lipids.
So the next question is, how do you know you have fatty liver disease? Well, this is quite tricky. Patients with steatosis, or fatty liver, alone, may exhibit no symptoms at all, in the early stages, although some might experience mild pain or tiredness. And, often, patients are only diagnosed when blood tests for an unrelated condition showed that their liver is injured. And this is a worry, because there are probably thousands of people with steatosis who don’t know about it and may not know, until their liver injury is more severe and they’ve developed full-blown NASH. Once this has occurred, the symptoms such as jaundice, itchiness, and cirrhosis accompany the failure of the liver.
So how can we identify patients with NAFLD at the stage when they can be treated easily? Well, often blood tests can give the clue. Some of the metabolic enzymes which line the hepatocytes can leak out into the bloodstream, when these cells get damaged. And these form the basis of the commonly performed liver function tests, or LFTs. A patient with an unexpectedly high result in this test, who has no other obvious cause of liver disease, such as viral infection or alcohol damage, may then be referred to a liver unit, for extra tests. Most commonly, ultrasound, MRI scans, or other imaging tests will show the presence of fat in the liver, and this can, then, be confirmed with a liver biopsy.
Once NAFLD has been diagnosed, the early stages can be managed effectively with simple moderation of diet and some exercise. In patients with other problems which have caused the fatty liver, such as diabetes or viral infection, the treatment of these conditions often helps the liver fat, too. There aren’t yet any good treatments that can specifically target fatty liver disease, but some agents which can modify how you handle fats– like statins in insulin sensitizers– are being investigated. Patients who have progressed to significant fibrosis, however, are harder to treat, and they may require liver transplantation.
So this brings us to our final question. Why should we be worried about fatty liver disease? Well, it’s because the rates are increasing so fast, and, as of yet, it’s hard to treat. Some data estimates that up to 50% of people in the European Union are obese and, thus, at risk of developing the disease. And this means that as many as 44% of the general population– which does include children– could be at risk. And this is significantly higher in the diabetic population. Patients with NAFLD have a significantly increased risk of dying from liver failure or cardiovascular disease. And also, the management of these patients is costly for health care providers. So NAFLD represents a significant global problem.
We’ll hear more about this, and the other global incidence of liver disease, next week.
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