Published online Feb 21, 2021. doi: 10.3748/wjg.v27.i7.609
Peer-review started: August 28, 2020
First decision: November 3, 2020
Revised: November 17, 2020
Accepted: December 28, 2020
Article in press: December 28, 2020
Published online: February 21, 2021
Processing time: 175 Days and 8.8 Hours
Non-alcoholic fatty liver disease affects 25% of the population worldwide and up to 30% in the Japanese population, and in some can progress to non-alcoholic steatohepatitis (NASH), a leading cause of liver transplant due to its strong propensity to develop into cirrhosis and hepatocellular carcinoma.
Liver biopsy is the current reference standard for a clinical diagnosis of NASH, a method that is expensive, invasive and suffers from great observer variability. Non-invasive and scalable alternatives are required in order to meet the burgeoning demands of the disease on clinical caseloads across the globe.
The main objectives of the study were to evaluate the diagnostic performance of non-invasive, image derived metrics to identify patients with suspected NASH. The metrics under investigation included two quantitative multi-parametric magnetic resonance imaging (MRI) measures, iron corrected T1 mapping [(cT1), a marker of fibro-inflammation] and proton density liver fat fraction (a marker of liver fat), magnetic resonance elastography and ultrasound based transient elastography (vibration-controlled transient elastography and 2D shear-wave elastography), both markers of liver stiffness.
In an observational study of patients who were being screened clinically on suspicion of NASH, n = 145 individuals underwent liver biopsy and concomitant imaging measures of liver health. Diagnosis of NASH was based on histology, graded using the NAS- Clinical Research Network scoring system and diagnostic accuracy of the image-derived metrics assessed using area under receiver operator characteristic curve. In addition, the biopsy slides were read by 2 further pathologists and comparisons made to explore the level of agreement on diagnosis between individual doctors.
In this study assessing the ability of different non-invasive biomarkers to detect NASH, MR liver fat and cT1 were superior to the other metrics investigated. Crucially however, the composite marker of cT1 and MR liver fat showed the greatest diagnostic accuracy for identifying those with NASH and also those with NASH with fibrosis. These measures also had very few technical failures. This is the first assessment and direct comparison of these technologies in a Japanese cohort. We also observed discordance between different pathologists across the four cardinal pathological features (steatosis, ballooning, lobular inflammation and fibrosis), with no common pattern of agreement seen between any two pathologists.
These results demonstrate the clinical utility of quantitative multiparametric magnetic resonance imaging (mpMRI) for the identification and stratification of patients with NASH from those with evidence of NAFLD and encourages mpMRI use as a non-invasive alternative to biopsy in the clinical care pathway. Quantitative mpMRI metrics showed the strongest correlation to the histological components of NASH with fewer technical failures. mpMRI also out-performed magnetic resonance elastography and ultrasound-based elastography methods in the identification of patients with NASH and fibrosis. Liver biopsy suffered from high levels of inter-reading disagreement, highlighting the pressing need for alternative diagnostic tests for NASH.
The ability to risk stratify patients in a single non-invasive test is a particular strength of mpMRI, offering a safe and cost-effective alternative to liver biopsy. Future work should be focused on validating these findings further and on longer term outcomes studies to investigate the prognostic natures of these measurements in a Japanese population.