Emerging concepts in the detection of liver fibrosis in non-alcoholic fatty liver disease

ABSTRACT

Introduction

The non-invasive identification of liver fibrosis related to Non-Alcoholic Fatty Liver Disease is crucial for risk-stratification of patients. Currently, the reference standard to stage hepatic fibrosis relies on liver biopsy, but multiple approaches are developed to allow for non-invasive diagnosis and risk stratification. Non-invasive tests, including blood-based scores and vibration-controlled transient elastography, have been widely validated and represent a good surrogate for risk stratification according to recent European and American guidelines.

Areas covered

Novel approaches are based on ‘liquid’ biomarkers of liver fibrogenesis, including collagen-derived markers (PRO-C3 or PRO-C6), or ‘multi-omics’ technologies (e.g. proteomic-based molecules or miRNA testing), bearing the advantage of tailoring the intrahepatic disease activity. Alternative approaches are based on ‘dry’ biomarkers, including magnetic resonance-based tools (including proton density fat fraction, magnetic resonance elastography, or corrected T1), which reach similar accuracy of liver histology and will potentially help identify the best candidates for pharmacological treatment of fibrosing non-alcoholic steatohepatitis.

Expert opinion

In the near future, the sequential use of non-invasive tests, as well as the complimentary use of liquid and dry biomarkers according to the clinical need (diagnosis, risk stratification, and prognosis, or treatment response) will guide and improve the management of this liver disease.

KEYWORDS:

• collagen-derived biomarkers
• liver fibrosis
• Non-Alcoholic Fatty Liver Disease
• non-invasive test
• magnetic resonance elastography
• PRO-C3
• PRO-C6
• proteomics

Article highlights

• In the Non-Alcoholic Fatty Liver Disease (NAFLD) landscape, liver fibrosis detection still requires liver biopsy, but multiple non-invasive approaches are being investigated;

• Current paradigms are based on the sequential use of non-invasive tests, mainly FIB-4 score followed by vibration-controlled transient elastography (VCTE), which is the most accurate non-invasive tool for the identification of significant liver fibrosis;

• Novel ‘liquid’ biomarkers include direct collagen-derived peptides (e.g. PRO-C3 and PRO-C6), which are promising tools for either the risk stratification or the prediction of treatment response;

• The use of advanced ‘dry’ markers, especially magnetic resonance-based tools (e.g. PDFF, MRE, and cT1) can identify with high accuracy steatosis grade and fibrosis stage and will help identify the best candidates for pharmacological treatments and support the prognostication.

Declaration of interest

Joern M. Schattenberg is a consultant for Apollo Endosurgery, Bayer, Boehringer Ingelheim, BMS, Gilead Sciences, GSK, Intercept, Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, and Siemens Healthineers. JMS has received research funding from Gilead Sciences, Boehringer Ingelheim, Siemens, and Healthcare GmbH. JMS has Stock Options in AGED diagnostics, Hepta Bio. JMS has received speaker honorarium from Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals, Histoindex, and MedPublico GmbH. JMS has received funding from the European Union Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under the grant agreement 777377: LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) and Screening for Liver Fibrosis. A population-based study in European countries. The ‘’LiverScreen’’ project (No 847989). Maurice Michel is supported by the Clinician Scientist Fellowship ‘Else Kröner Research College: 2018_Kolleg.0.’ The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.