Non-invasive methods for imaging hepatic steatosis and their clinical importance in NAFLD

Hepatic steatosis is a key histological feature of nonalcoholic fatty liver disease (NAFLD). The non-invasive quantification of liver fat is now possible due to advances in imaging modalities. Emerging data suggest that high levels of liver fat and its temporal change, as measured by quantitative non-invasive methods, might be associated with NAFLD progression. Ultrasound-based modalities have moderate diagnostic accuracy for liver fat content and are suitable for screening. However, of the non-invasive imaging modalities, MRI-derived proton density fat fraction (MRI-PDFF) has the highest diagnostic accuracy and is used for trial enrolment and to evaluate therapeutic effects in early-phase clinical trials in nonalcoholic steatohepatitis (NASH). In patients with NAFLD without advanced fibrosis, high levels of liver fat are associated with rapid disease progression. Furthermore, changes on MRI-PDFF (≥30% decline relative to baseline) are associated with NAFLD activity score improvement and fibrosis regression. However, an inverse association exists between liver fat and complications of cirrhosis. Liver fat decreases as liver fibrosis progresses towards cirrhosis, and the clinical importance of quantitative measurements of liver fat differs by NAFLD status. As such, patients with NAFLD should be stratified by fibrosis severity to investigate the utility of quantitative measurements of liver fat for assessing NAFLD progression and prognosis. Imaging modalities are now available that enable non-invasive quantitative measurements of liver fat content. This Review highlights the various modalities and their use in clinical trials, discusses the clinical importance of hepatic steatosis for progression of nonalcoholic fatty liver disease and proposes how the new modalities might be used going forward. Key points Ultrasound-based modalities for the quantification of liver fat content have moderate diagnostic accuracy for the degree of hepatic steatosis and are useful as a pre-screen strategy in clinical trials in nonalcoholic steatohepatitis (NASH). Compared with other imaging modalities, MRI-derived proton density fat fraction (MRI-PDFF) has the highest diagnostic accuracy for quantification of liver fat content and is commonly used in trials in NASH. Increased liver fat content (MRI-PDFF ≥15%) is associated with increased odds of fibrosis progression in patients with NAFLD at an early stage of fibrosis. In patients with NAFLD, change in MRI-PDFF (≥30% decline rel