[MUSIC] In NAFLD, there's no single test, which can tell us if the patient has NAFLD. The diagnosis requires careful review of the medical history, the physical examination and diagnostic tests. I have therefore asked Professor Flemming Bendtsen, from the gastro unit at Hvidovre Hospital, about the current evidence and guidelines for clinical practice. So Flemming, thank you very much for taking time to talk to us about diagnostic tests in NAFLD. What I'd like to know is what are the first steps that you do when you want to assess if a patient who comes to your clinic has NAFLD. Unfortunately, NAFLD is not characterized by specific symptoms or by a specific clinical presentation. So often we base it on what we get of information from the patients together with a physical examination, and then we have a need of also to take some blood tests. There's not a single blood test, which is able to define NAFLD, so it's often a combination of the three findings, of the clinical examination, the symptoms and also a variety of blood tests. So we try to combine all these and we also look for comorbidities in the patient because they can be very meaningful in the diagnosis, and we also get a good history of previous medication because medication can influence on the liver function and also on blood tests. Liver blood tests are used to evaluate liver function and the extent of damage and inflammation in the liver. These tests were previously referred to as liver function tests, but research show that many patients with elevated liver blood tests have a normal liver function. The main liver blood tests express enzymes, proteins and other substances that are produced in the liver. Two of the most commonly used tests are the two enzymes, alanine aminotransferase and aspartate aminotransferase, or ALT and AST which are produced in the hepatocytes and leaked into the bloodstream when the liver cells are damaged. ALTs are almost exclusively produced in the liver and is more specific than the AST, which we can find in other organs. This means that an increased concentration is more likely to be false positive. One example is muscle damage which can lead to elevated AST. Elevation of the enzymes alkaline phosphatase and gammaglutamyl-transferase can indicate obstruction or cholestatic liver disease. Bilirubin, which is produced following the breakdown of red blood cells and excreted into the bile can also indicate cholestatic liver disease as well as severe inflammation or affected liver function, such as alcoholic hepatitis. Albumin, which is a protein and the INR or the prothrombin time, which are clotting factors are also produced in the liver. Assessment of the albumin and INR levels are important when evaluating patients with liver disease because abnormal results indicate an impaired liver function. The fibrosis-4 or FIB-4 score is calculated based on the age, multiplied by the AST and divided by the platelet count, multiplied by the square root of the ALT. If your patient has NAFLD, a FIB-4 score below 1.45 indicates that the patient is unlikely to have significant fibrosis. A score higher than 2.67 indicates a high risk of significant fibrosis or cirrhosis. And we know that fibrosis of the liver is the most important prognostic sign. So we follow the patients and often repeatedly with an analysis of the FOUR scores. There's also other scores, but that's the most used by us, and you can quite easily go on the internet and find calculation of the FOUR score. The abdominal ultrasound is often the first step used when assessing patients with elevated liver blood tests. For patients with at least 20% steatosis, the ultrasound can identify steatosis and provide essential information to guide the diagnostic plan. Sonographic signs of NAFLD include bright hepatic echoes, increased hepatorenal echogenicity and vascular blurring of the portal or hepatic veins. The fiber scan is a specialized ultrasound machine, which uses shear wave velocity. A 50 megahertz wave is passed into the liver from a small transducer on the end of the ultrasound probe. The probe measures the velocity of the shear wave when it passes through the liver. The shear wave velocity can then be converted into liver stiffness, which is associated with the degree of fibrosis or scarring of the liver. The fibroscan can also be used to assess the degree of steatosis via the ultrasound attenuation. The measurement is expressed by the Controlled Attenuation Parameter or CAP, which ranges from 150 - 400. Patients with NAFLD values from about 300 - 400. The percutaneous liver biopsy is used to acquire tissue for histology assessment. Before the biopsy, the position, and needle entry point is determined with an ultrasound. Potential complications include pain and bleeding. The transjuguler liver biopsy is associated with a low risk of bleeding, and can be undertaken in patients with an increased risk of bleeding as well as patients with ascites. Initially, the right jugular vein is identified with ultrasound guidance. Subsequently, a catheter is inserted into the jugular vein and guided to the hepatic vein with x-ray guidance. A liver biopsy can subsequently be collected. So there are other options apart from the blood test diagnostic imaging. Do you sometimes combine that with your blood tests? When we get patients referred, we normally always combine it with imaging. The first imaging we will do, that would be an ultrasound of the liver. Ultrasound is not that sensitive because you need to have at least presence of 20% infiltration of fat in the liver before an ultrasound show signs of steatosis. So there just needs to be a significant amount of fat in the liver before it shows that, and it cannot be used for inflammation or presence for fibrosis. Sometimes you can see if there is cirrhosis on the ultrasound. So the ultrasound again cannot stand alone. We often combine it with fibroscan or elastography, and that's a special tool. By that you send a wave through the liver, and the reflection of the wave measures how the elasticity of the liver is. If you come over a certain threshold you can be sure that there is actually presence of what you can call F3 or F4. So it's good to show significant fibrosis. We almost all use it in all of our patients referred for fatty liver disease. What about mild fibrosis, is it good? It's not that good in the diagnosis of mild fibrosis. It's quite good when you have a normal architecture of the liver and it's also good to discriminate patients with F3 or F4, that will say severe fibrosis or presence of cirrhosis. Are there any other imaging techniques that you sometimes use? Some people use MRI magnetic resonance imaging Yeah, we also do that or maybe not that often in clinical practice, but MRI elastography might have an even higher sensitivity for the presence of fibrosis, than the elastography by fibroscan. And also, you can combine it with MR spectroscopy, which can show the fat infiltration in the liver and has a quite higher sensitivity than ultrasound in the diagnosis of fatty liver disease, without inflammation or presence of fibrosis. So Flemming, when you add up all of this information from your scans and your blood samples, and you suspect that a patient has advanced fibrosis, how do you proceed? First of all, I need to be sure that I've excluded all other causes of liver disease, for example, autoimmune liver disease. Then if I see a patient, if a patient has clinical signs like FIB-4 score or if they have elastography, showing that they have signs of F3 or F4, I would normally always go further with a biopsy of the liver to confirm the presence of the fibrosis but also to exclude other causes of liver diseases which might be present. And when I have my biopsy, the biopsy of the patients, I will decide how to follow this patient up to optimize the medication or even change medication and finally to make a follow-up program for the patient. Because these patients, they need to be followed up in long term in the outpatient clinic. Thank you very much Flemming. It was a pleasure. [MUSIC]
