• NONALCOHOLIC STEATOHEPATITIS
• MACROPHAGES
• INFLAMMATION
• FIBROSIS

Clinical diagnosis, selection of patients in non-alcoholic steatohepatitis (NASH) clinical trials and evaluation of both disease progression and the impact of therapeutic strategies rely on histological assessment of disease activity and fibrosis stage. Disease activity drives fibrosis progression and is reflected in the NAFLD Activity Score (NAS) and Steatosis, Activity and Fibrosis (SAF)-A histological scores, which sum steatosis, lobular inflammation and hepatocellular ballooning. Fibrosis stage reflects the accumulation of fibrosis and progression to cirrhosis and is associated with liver-related clinical outcomes.1 Liver biopsy is invasive, carries a small but measurable risk of complications, is unsuitable for wide screening at the population level, and is subject to sampling heterogeneity and interobserver and intraobserver discrepancies, which lead to errors in diagnosis and staging, as well as to high rates of screening failure in NASH clinical trials.1 Several non-invasive methods to quantify NASH disease activity and fibrosis have been developed.2 MRI-estimated proton density fat fraction (PDFF) accurately quantifies hepatic steatosis and is used in clinical trials to measure treatment response. Shear wave elastography (SWE; FibroScan, pSWE/Acoustic Radiation Force Impulse (ARFI), two-dimensional (2D) SWE) and magnetic resonance elastography (MRE) identify F3–F4 advanced fibrosis, but their use may be limited by the patients’ body habitus, as well as their costs and availability. Serum-based protein assays (eg, cytokeratin-18 fragments, collagen neoepitope PRO-C3), multiparameter …