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Editorial: further evidence for the use of advanced magnetic resonance imaging techniques to monitor NAFLD – authors’ reply

We thank Drs. Mansour and McPherson for their editorial summary and insightful comments on our paper exploring the utility of advanced magnetic resonance imaging (MRI) measures in assessing for treatment response in non-alcoholic steatohepatitis. 2 As they have pointed out, the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) has profound public health implications, spawning numerous clinical trials over the past decade. In order to transcend the various shortcomings of the liver biopsy and minimise the risks involved to patients, we believe MRI techniques may be the next gold standard for assessing steatosis and fibrosis. In our previous work, we have compared several novel imaging modalities to liver biopsy for the assessment of steatosis, including quantitative ultrasound and MRI-proton density fat fraction (PDFF). In a previous study, we showed that MRI-PDFF is more sensitive than liver histology for detecting incremental, longitudinal changes in hepatic fat content. Our present student expands on this trend, looking at total liver volume (TLV) and the total liver fat index (TLFI), derived from the same scan. We agree with the editorial authors that the lack of relationship between change in histological steatosis and total liver volume may be in part due to methodology, whereby our histological grade of steatosis was categorical (grade 1–3) rather than continuous (percentage steatosis). In future studies, we will consider this nuance and expand our methodology, and sample size, to further examine this relationship. We agree that fibrosis is a major determinant for classifying high-risk patients. Both the degree and trend of fibrosis in these patients with NASH – especially as we study potential therapies – is an increasingly important endpoint. Indeed, various studies are showing that the risk of liver-related mortality increase exponentially with higher fibrosis stages. While transient elastography (TE, or “FibroScan”) is generally more accessible, body habitus and volume overload (findings frequently found among this patient group often with cardiovascular comorbidities) can affect its overall accuracy. While this study did not show a statistically significant relationship between PDFF, TLV, and TLFI with histological fibrosis, we have studied in other trials the utility of MR elastography, a different type of MRI-based exam involving shear waves to evaluate liver stiffness. It has been shown to be more accurate for measuring fibrosis than TE when compared with histology, with an AUROC of 0.957 when compared with eight other clinical prediction rules for advanced fibrosis. The nuances between the various advanced MRI techniques remain to be fully elucidated. As we continue to unravel these nuances, we recently showed that 3D-MRE may be more accurate than 2D-MRE in assessing advanced fibrosis. With our present study, we believe there may be utility in assessing (changes) in liver volume and calculating total liver fat burden as well.