MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of nonalcoholic steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms.

Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease

“…[23][24][25][26][27][28][29] Although MRI-based techniques have shown to be accurate and effective in patients with obesity, 30 they are more expensive and not widely available compared to TE. 31 A recent Japanese study by Imajo et al 32 directly compared and demonstrated that MRE and MRI-PDFF have higher accuracy than TE and CAP, respectively, for diagnosing fibrosis and steatosis in NAFLD patients. However, this study assessed TE using only the M probe.…”

Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis

“…Participants were considered to have NAFLD-related cirrhosis if they had NAFLD according to the definition above and had biopsy-proven cirrhosis (histology fibrosis stage 4). We have previously validated that a liver stiffness cut point greater than 3.63 kPa on MRE provides an accuracy of 0.92 for the detection of advanced fibrosis, and it is the most accurate noninvasive test for the diagnosis of advanced fibrosis (29,(37)(38)(39). Advanced fibrosis among first-degree relatives was determined by either imaging evidence of nodularity and presence of intraabdominal varices or other imaging evidence of portal hypertension or liver stiffness assessment with MRE threshold ≥3.63 kPa (28,29,34).…”

A Fibroblast Growth Factor 21–Pregnane X Receptor Pathway Downregulates Hepatic CYP3A4 in Nonalcoholic Fatty Liver Disease

“…In this regard, the development of methodologies such as magnetic resonance imaging and elastography (Dulai et al, 2016) that could replace the gold-standard liver biopsy for the diagnosis and staging of the disease will greatly facilitate future clinical studies aimed at examining the clinical relevance of lower CYP3A4 activity in the NAFLD population. Likewise, additional studies are necessary to confirm the role of FGF21 in regulating CYP3A4 in NAFLD.…”