Hepatology

Liver Fibrosis

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Imaging- and Blood-Based Markers of Hepatic Fibrosis and Cirrhosis

clinical topic updates by Raymond T. Chung, MD

Overview

Noninvasive tests for liver fibrosis are becoming increasingly validated in clinical practice and, in many cases, may supplant the performance of liver biopsy. Combining imaging- and blood-based tests can increase our confidence in the noninvasive assessment of liver fibrosis.

Expert Commentary

Raymond T. Chung, MD

Director of Hepatology and the Liver Center
Vice Chief of Gastroenterology
Massachusetts General Hospital
Professor of Medicine
Harvard Medical School
Boston, MA

“We are moving quickly toward a world in which biopsy could be obviated by the availability of noninvasive tests for fibrosis.”

Raymond Chung, MD

There is an increasing movement toward the use of noninvasive tests to assess fibrosis stage in patients with chronic liver disease. Liver biopsy, long considered to be the gold standard for the assessment of fibrosis, is logistically impractical and is associated with meaningful risk. Among the histologic information obtained from biopsy in NASH and other conditions, fibrosis is the single most important prognostic determinant of clinical outcome; therefore the, accurate assessment of fibrosis becomes paramount. 

Efforts in the serum space have included the Fibrosis-4 (FIB-4) score, a 4-variable index consisting of aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, and age, as well as the AST to Platelet Ratio Index (APRI). Both the FIB-4 and the APRI use routinely obtained variables and can easily be calculated without the need for a laboratory send out. These assays are accurate, particularly at the extremes of fibrosis (ie, early and advanced fibrosis). The FIB-4 and the APRI perform in a similar manner and have gained good uptake among practitioners. Other blood-based biomarker tests include FibroTest (Biopredictive Paris)/FibroSure (Labcorp) and the Enhanced Liver Fibrosis (ELF) test (Siemens Healthineers). These are proprietary tests that involve laboratory send outs that are billed to insurance. 

Simple serum-based tests such as the FIB-4 perform with good accuracy, although their utility principally resides in their negative predictive value in excluding patients with advanced fibrosis. In this regard, we can effectively obviate the need for screening for hepatocellular carcinoma and for portal hypertension. The FIB-4 performs well at the extremes, but not as well in the intermediate zones, between no to minimal fibrosis and advanced fibrosis.

In general, serum-based tests can be coupled with an imaging-based marker that reflects the stiffness of the liver using a technique known as elastography. Elastography can be performed through different modalities, including ultrasound, magnetic resonance imaging, and vibration-controlled transient elastography (FibroScan [Echosens]), the latter of which has gained widespread uptake in practice. FibroScan has very good accuracy and is straightforward to use, taking approximately 10 minutes in the office. As with serum tests, the performance of elastography is very accurate at the extremes of fibrosis and is less accurate in the intermediate zones. Sometimes an imaging-based study is coupled with a blood-based study, and, when results of both studies are concordant, this can increase our confidence that the results accurately characterize the fibrosis stage. Concordant results may also constitute a basis for longitudinal follow-up for tracking fibrosis progression.  

We are moving quickly toward a world in which biopsy could be obviated by the availability of noninvasive tests for fibrosis. Such testing is becoming increasingly validated in clinical practice and may supplant the performance of liver biopsy for patients with known liver disease. The argument has been made that one may obtain even more reliable information from an integrated assessment with the use of noninvasive imaging tests such as magnetic resonance elastography than what one might obtain with tissue biopsy, which may be subject to sampling error given the patchiness of fibrosis. Therefore, biopsy, our historical gold standard, may, in fact, not be so gold at the end of the day. Further, noninvasive assessment can be used not only for cross-sectional staging but also straightforwardly for longitudinal follow-up in patients with known liver disease. 

References

Ajmera V, Loomba R. Imaging biomarkers of NAFLD, NASH, and fibrosis. Mol Metab. 2021;50:101167. doi:10.1016/j.molmet.2021.101167

Gheorghe G, Bungău S, Ceobanu G, et al. The non-invasive assessment of hepatic fibrosis. J Formos Med Assoc. 2021;120(2):794-803. doi:10.1016/j.jfma.2020.08.019

Heyens LJM, Busschots D, Koek GH, Robaeys G, Francque S. Liver fibrosis in non-alcoholic fatty liver disease: from liver biopsy to non-invasive biomarkers in diagnosis and treatment. Front Med (Lausanne). 2021;8:615978. doi:10.3389/fmed.2021.615978

Masuzaki R, Kanda T, Sasaki R, et al. Noninvasive assessment of liver fibrosis: current and future clinical and molecular perspectives. Int J Mol Sci. 2020;21(14):4906. doi:10.3390/ijms21144906

Sanyal A, Shankar A, Yates K, et al. Primary results of the NIMBLE stage 1-NASH CRN study of circulating biomarkers for nonalcoholic steatohepatitis and its activity and fibrosis stage [abstract LO1]. Abstract presented at: AASLD The Liver Meeting; November 12-15, 2021.

Schuppan D, Myneni S, Surabattula R. Liquid biomarkers for fibrotic NASH – progress in a complex field. J Hepatol. 2022;76(1):5-7. doi:10.1016/j.jhep.2021.11.005 2021.

Raymond T. Chung, MD

Director of Hepatology and the Liver Center
Vice Chief of Gastroenterology
Massachusetts General Hospital
Professor of Medicine
Harvard Medical School
Boston, MA

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