Nonalcoholic fatty liver disease: use of diagnostic biomarkers and modalities in clinical practice

ABSTRACT

Introduction:

The global burden of liver disease is increasing, and nonalcoholic fatty liver disease (NAFLD) is among the most common chronic liver diseases in Asia, Europe, North and South America. The field of noninvasive diagnostic and their role in staging, but also predicting outcome is evolving rapidly. There is a high-unmet need to stage patients with NAFLD and to identify the subset of patients at risk of progression to end-stage liver disease.

Areas covered:

The review covers all established diagnostic blood-based and imaging biomarkers to stage and grade NAFLD. Noninvasive surrogate scores are put into perspective of the available evidence and recommended use. The outlook includes genetics, combined algorithms, and artificial intelligence that will allow clinicians to guide and support the management in both early and later disease stages.

Expert opinion:

In the future, these diagnostics tests will help clinicians to establish patient care pathways and support the identification of relevant subgroups for monitoring and pharmacotherapy. In addition, researchers will be guided to better understand available scores and support the development of future prediction systems. These will likely include multiparametric aspects of the disease and machine learning algorithms will refine their use and integration with large datasets.

KEYWORDS:

• Noninvasive tests
• advanced liver fibrosis
• liver disease
• diagnostic biomarker
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis
• cirrhosis
• test accuracy
• machine learning

Abbreviations

Non-invasive tests (NITs); Nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH); type 2 diabetes (T2D); Hepatic Steatosis Index (HSI); aspartate transaminase (AST); alanine transaminase (ALT), BMI (Body Mass Index); area under the receiver-operating characteristic curve (AUROC); gamma-glutamyl transferase (GGT); NAFLD Liver Fat Score (NLFS); Lipid Accumulation Product (LAP); Magnet resonance imaging (MRI); AI’s (Artificial Intelligence); H-MRS (Proton Magnetic Resonance Spectroscopy); negative predictive value (NPV); Computer Tomography (CT); Controlled Attenuation Parameter (CAP); MRS (Magnetic Resonance Spectroscopy); MRI-proton density fat fraction (MRI-PDFF); cytokeratin 18 (CK18); interleukin (IL); C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), cathepsin D (CatD); Patatin-like phospholipase domain-containing protein 3 (PNPLA3); NAFLD Activity Score (NAS); NAFLD Fibrosis Score (NFS); vibration-controlled transient elastography (VCTE); transient elastography (TE); magnetic resonance elastography (MRE); liver multiscan (LMS); NASH-CRN (Clinical Research Network); Fibrosis-4 Score (FIB-4); positive predictive value (PPV); AST-to-Platelet Ratio Index (APRI); Enhanced Liver Fibrosis (ELF) Score; tissue inhibitor of metalloproteinase 1 (TIMP-1); procollagen III amino-terminal peptide (PIIINP); Procollagen-3 (PRO-C3); shear wave elastography (SWE); acoustic radial force imaging (ARFI); Advanced Fibrosis (AF); point-SWE (pSWE); transmembrane 6 superfamily member 2 (TM6SF2); membrane-bound O-acetyltransferase domain-containing protein 7 (MBOAT7); glucokinase regulatory protein (GCKR).

Article Highlights

• NAFLD can be staged using non-invasive tests (NITs)

• The references standard liver histology in NAFLD will be abandoned in clinical practice, but is required as surrogate endpoint in regulatory trials

• Binary surrogate scores guide in ruling-in and ruling-out advanced fibrosis from NAFLD

• Sequential testing strategies are employed to rescue indeterminate ranges

• Artificial intelligence will refine and improve the testing and diagnosis strategies

Declaration of interest

JMS reports Consultancy: Boehringer Ingelheim, BMS, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Madrigal, Novartis, Novo Nordisk, Nordic Bioscience, Pfizer, Roche, Sanofi, Siemens Healthcare GmbH . Research Funding: Gilead Sciences, Boehringer Ingelheim. Speakers Bureau: Falk Foundation MSD Sharp & Dohme GmbH.

Reviewer disclosures

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

Additional information

Funding

JMS is partly funded by the European Union Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement 777377: LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) and the ‘LiverScreen’ project (grant agreement No 847989).