Non-Invasive biomarkers (blood tests) for NAFLD (non-alcoholic fatty liver disease)

The diagnostic modalities for NAFLD have recently been reviewed in an accepted paper issued by AASLD Emerging Trend Conference on NASH on the state of diagnostic modalities for NASH and fibrosis (awaiting full publication). This post tries to put this into context for the non-specialist.

Click on the image to enlarge (with links).

In a previous post we addressed the silent epidemic of NAFLD. NAFLD includes both NASH (non-alcoholic steatohepatitis) and NAFL (fatty liver without inflammation).  Fatty infiltration of the liver is an increasingly more common imaging finding on ultrasound and CT scans. In fact, it is now so frequent that it is often ignored. While in most cases only fatty liver without inflammation (NAFL) is present, some patient will have NASH, non-alcoholic steatohepatitis, a disease that can progress to end-stage liver disease. How does one make the distinction? First off, most patients with fatty liver should have a standard liver disease panel done, especially if the transaminases are elevated, other causes of liver disease needs to be ruled out before a diagnosis of NAFLD is made. As part of this process, a liver disease etiology panel should be obtained.

NASH or just fatty liver?

Once a diagnosis of NAFLD has solidified, a distinction between NASH and simple fatty liver (NAFL) needs to be attempted. Without a liver biopsy this can sometimes be hard. Normal imaging cannot tell what caused the fatty liver, whether there is steatohepatitis (NASH) or not, and if fibrosis, an important prognosis factor, is present.  Not everybody with mildly elevated transaminase will have NASH, and, conversely, if the transaminases are normal, NASH can still be present. It is important to take diseases that define the metabolic syndrome into consideration as those increase the risk of having NASH.


Liver biopsy is the gold standard – what are the alternatives?

Liver biopsy is the only fully reliable test that can differentiate NASH from NAFL and assess the degree of fibrosis in NASH, an important prognostic factor. However, there are many reasons why liver biopsy is not a high priority, both from a patient’s and physician’s perspective. Magnetic resonance elastography and US elastography (transient elastography, acoustic radiation force impulse imaging, supersonic shear-wave imaging, and real-time tissue elastography) are modalities that are helpful in assessing fibrosis. At the time of this writing these tests are not available in San Luis Obispo County.  This leaves us, and most patients anywhere, with serum biomarkers.

Serum biomarkers (blood tests) for fibrosis in NAFLD

Please refer to the dynamic image (clickable links) that accompanies this post.  Serum biomarkers can be classified in many ways. Of great practical significance is whether they purport to diagnose NASH (left side of panel), an endeavor which has largely failed so far, and whether they try to assess the degree of fibrosis (“Fibrosis Markers”), which is more promising. Some of them are multi-panel tests that measure several biomarkers that reflect collagen turnover (“Collagen Turnover”) offered by commercial labs, and those which reflect fibrosis indirectly and consists of standard laboratory tests and other information that is readily available (NAFLD Fibrosis score, FIB4 score). Especially the NAFLD Fibrosis score can be helpful in clinical practice: Using a low cut-off (< -1.455), advanced fibrosis can be ruled out (NPV 93%). A high cut-off (>0.676) detects advanced fibrosis with accuracy (PPV 90%). This may reduce the need for liver biopsy by 75 %.

Dr. Klaus Gottlieb is a gastroenterologist with a special interest in liver disease.  He practices in San Luis Obispo, CA, and Templeton, CA. Follow this link to make an appointment.



Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwander‐Tetri BA, Serfaty L, Negro F, Caldwell SH, Ratziu V. Diagnostic Modalities for Non‐alcoholic Fatty Liver Disease (NAFLD), Non‐alcoholic Steatohepatitis (NASH) and Associated Fibrosis. Hepatology. 2017 Dec 9. Manuscript online, awaiting full publication. DOI: 10.1002/hep.29721





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