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Liver Biopsy in Advanced Fibrosis Due to NASH


Expert clinicians remark on the current role of the liver biopsy in the diagnosis of advanced fibrosis due to nonalcoholic steatohepatitis and highlight considerations for utilizing newer, noninvasive testing procedures instead.


Viviana Figueroa Diaz, MD: For the diagnosis of NASH [nonalcoholic steatohepatitis], you need a liver biopsy because, by definition, it’s nonalcoholic steatohepatitis, and that’s a word that you can use only if you have a pathology sample. Otherwise, we call it nonalcoholic fatty liver disease [NAFLD]. It depends what stage you are in, in regard to diagnosing or screening the patient. You can use noninvasive tools to look for advanced fibrosis.

Liver biopsy, in general, to diagnose anything in liver disease, including NASH, can have complications like any invasive procedure that we do to our bodies. Some of the complications include bleeding, infection, and perforation of other organs, depending on the direction of the needle. Right now, those risks are low. Those risks are small because we use radiology to guide the needle, but otherwise those are some of the things that could happen in terms of complications.

Mazen Noureddin, MD: Some of the complications that are associated with a liver biopsy include having pain, bleeding, and very rarely death. However, patients are really scared of it. They don’t want to go through the pain and/or rare episodes of bleeding. In addition, a liver biopsy is costly. It requires radiology. It requires going to an outpatient procedure. The patient is kept for a few hours, which may be a huge inconvenience for them. That’s why none of these tests has been investigated thoroughly.

Although it might be available in many areas, there are multiple issues with it as well, like the availability of the pathologist who’s going to read it. This pathologist should be familiar with NAFLD and NASH. As I said, there are very large number of these patients. Once therapies become available, it might become impractical to do liver biopsies on these patients. It’s costly, and it is not accessible to everyone. That’s why the research for noninvasive testing has been very active and has shown good results.

Some of the noninvasive diagnostic tests that have been used in NAFLD and NASH, especially to look for advanced fibrosis, can be divided into 2 categories. The first is imaging based, and the second is serum based. Let’s start with those that are endorsed by the American Association for the Study of Liver Diseases. They endorsed FIB-4 [fibrosis 4], the NAFLD fibrosis score, transient elastography, and MR [magnetic resonance] elastography. If we want to talk about imaging, the most common are transient elastography and MR elastography. Transient elastography is an ultrasound machine that can detect steatosis, as well as fibrosis, or stiffness. It gives you a quantitative measure of these 2 components: steatosis and fibrosis. In addition, you can follow these measurements longitudinally to see if there are any changes.

MR elastography is an MRI [magnetic resonance imaging]—based test that uses special software to detect stiffness of the liver that reflects fibrosis. Actually, it can be combined with another software called MRI proton density fat fraction [PDFF] that quantifies fat as well. Combining these methods can also give you an accurate idea about steatosis and fibrosis reflected by stiffness.

Pros and cons: One of the problems with the MR elastography and PDFF is that they are costly and require the participation of specialized centers. If we’re going to talk about the serum-based, FIB-4, and NAFLD fibrosis score, they’re endorsed by American Association for the Study of Liver Diseases. FIB-4 relies on simple blood testing—platelet count, ALT [alanine aminotransferase], AST [aspartate aminotransferase]—and patient’s age. So does the NAFLD fibrosis score, which also includes the addition of diabetes status. It can be calculated via the labs that you have in regular visits.

Viviana Figueroa Diaz, MD: Noninvasive testing is actually pretty effective. We use transient elastography and MR elastography, for example. They tend to be pretty accurate. Having said that, they are still noninvasive methods, so they can have overestimation and even underestimation, in some cases, of fibrosis.

In terms of blood testing for trying to determine how much fibrosis there is, you could use a liver panel that includes the liver enzymes and also look at a CBC [complete blood count] panel with platelets. There are other more commercialized blood samples you could use. With algorithms, you can combine the results of those numbers and determine if there could be advanced fibrosis without having to do a liver biopsy—or even a transient elastography, which is a noninvasive method.

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