Imaging-Based Assessment of Steatosis, Inflammation and Fibrosis in NAFLD

Curr Hepatology Rep https://doi.org/10.1007/s11901-017-0368-4 FATTY LIVER DISEASE (S HARRISON AND J GEORGE, SECTION EDITORS) Imaging-Based Assessment of Steatosis, Inflammation and Fibrosis in NAFLD Timothy Hardy 1,2 & Stuart McPherson 2,3 # The Author(s) 2017. This article is an open access publication Abstract Purpose of Review Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world. Invasive liver biopsy remains the gold standard method for the diagnosis and staging of NAFLD. The aim of this review is to summarize recent research regarding imagingbased assessment of NAFLD. Recent Findings Novel methods such as controlled attenuation parameter (CAP) and magnetic resonance imaging proton-derived fat fraction (MRI-PDFF) appear promising for steatosis assessment and are currently undergoing validation in NAFLD. Fibrosis can be non-invasively assessed by transient elastography (TE), which is currently the best validated test in NAFLD. MR elastography (MRE) appears very sensitive for fibrosis detection. No imaging technique can accurately detect NASH. Summary TE is inexpensive and relatively widely available and can reliably exclude advanced fibrosis in NAFLD. MRI offers the most promise for steatosis and fibrosis quantification, but further validation of these techniques is needed. This article is part of the Topical Collection on Fatty Liver Disease * Stuart McPherson 1 Gastroenterology, North Tees University Hospital, Stockton, UK 2 Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK 3 Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Level 6, Freeman Road, Newcastle Upon Tyne NE7 7DN, UK Keywords NAFLD . Steatosis . Fibrosis . Magnetic resonance imaging . Transient elastography . Imaging . Non-invasive test . Ultrasound Introduction Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide and is estimated to affect 25% of the global population [1]. NAFLD is strongly associated with obesity, and its prevalence has dramatically increased in the last few decades in parallel with rates of obesity. The histological definition of NAFLD is the presence of triacylglycerol (TAG) droplets in > 5% of hepatocytes, in the absence of excessive alcohol consumption or the use of steatogenic drugs [2]. Histologically, NAFLD ranges in severity from steatosis alone (frequently know as non-alcoholic fatty liver; NAFL) to steatohepatitis (known as non-alcoholic steatohepatitis; NASH), where steatosis is associated with hepatocellular injury, inflammation and fibrosis. Approximately 40% of patients with NAFLD will develop progressive fibrosis, which can result in cirrhosis [3, 4]. The incidence of NAFLD-related cirrhosis complications, such as hepatocellular carcinoma and portal hypertension, is increasing, and as a result, NAFLD is projected to be the primary indication for liver transplantation in the US by 2020 [5]. NAFLD has a variable prognosis with the majority of patients having benign disease without associated liverrelated morbidity or mortality. It has been recently determined that the key factor predicting long-term prognosis in patients with NAFLD is the stage of liver fibrosis [6, 7]. Recent studies have shown that individuals with advanced fibrosis (F3–F4) due to NAFLD have a > 3-fold increased risk of all-cause mortality, compared with a reference Curr Hepatology Rep population [6, 7]. Therefore, assessment of liver fibrosis is critical in all patients with NAFLD to determine prognosis and appropriate management. Liver biopsy remains the gold standard test to diagnose and stage NAFLD, but it has many well-documented limitations including the risk of complications, sampling error, inter- and intra-observer variability in reading the histology and the expense of the procedure [8]. Given the large burden of NAFLD worldwide, there is a critical need for simple and accurate non-invasive tests to diagnose hepatic steatosis and stage liver fibrosis. This will help identify individuals at the highest risk of progression so they can be targeted for more aggressive lifestyle interventions or treatments to slow disease progression. There is also an urgent need for accurate quantitative non-invasive tests for steatosis, hepatic inflammation and fibrosis to monitor response to treatment. This is particularly important with the recent development of several new drugs for NAFLD that are going through advanced-phase clinical trials. Currently, there is reliance on liver biopsy to monitor patients in the clinical trials, but this will not be practical once these drugs are widely used. There have been a number of recent advances in imaging-based assessment of steatosis and fibrosis which are likely to impact on clinical practice. This review aims to highlight some of the recent, important advances in this field and to discuss how these may change clinical practice. Radiographic Assessment of Steatosis Ultrasound Due to its wide availability and low cost, conventional ultrasound is the most common first line tool for the assessment of hepatic steatosis. A fatty liver appears “bright” compared with surrounding structures due to hepatic TAG deposition, resulting in increased acoustic interfaces. A recent meta-analysis including 2815 patients from 34 studies assessed the diagnostic accuracy of ultrasound compared with histology in patients with NAFLD. Overall, ultrasound had reasonable sensitivity and specificity (84.8 and 93.6%, respectively) for detecting > 20– 30% steatosis [9]. The sensitivity of ultrasound for detecting milder steatosis (5–10%) on liver biopsy was lower, with values as low as 65% [9]. Ultrasound was also inaccurate in differentiating fatty liver alone, from NASH and liver fibrosis [9]. A clear limitation of ultrasound is its operator dependency, and future studies should include detailed reliability assessments, which are currently lacking. Despite this, ultrasound remains a good first line imaging modality for the assessment of fatty liver. However, as ultrasound is insensitive for mild steatosis, if an individual is strongly suspected of having NAFLD clinically and the ultrasound is reported as normal, then second line imaging modalities should be considered to reduce missed diagnoses. Controlled Attenuation Parameter Grading and Staging of Liver Histology as the Reference Standard Table 1 shows the histological grading system for NAFLD that is used as the reference standard in most of the recent imaging studies. In the majority, imaging is compared with liver biopsy using semi-quantitative scales for grading steatosis (S0–3) and staging fibrosis (F0–4). Table 1 Histological grading of steatosis and staging fibrosis, according to the NASH CRN [60] Steatosis grade (S0–3) Fibrosis (F0–4) S0: 0–5% S1: 5–33% F0: None F1a: Zone 3 mild perisinusoidal F1b: Zone 3 moderate perisinusoidal F1c: Periportal/portal o (...truncated)