LiverMultiScan® could be an alternative to liver biopsy for NASH clinical trials.
- February 04, 2021
Oxford, United Kingdom, February 4th, 2021. A recent study demonstrates the potential for non-invasive measures of liver fibro-inflammation and fat, provided by Perspectum’s LiverMultiScan®, to detect pharmacodynamic changes in non-alcoholic steatohepatitis (NASH), potentially offering a safe alternative to liver biopsy for late-stage clinical trials.
Non-alcoholic fatty liver disease (NAFLD) and its more severe sub-type, NASH, are growing health concerns worldwide. The estimated worldwide prevalence is reported to be 25% and 3%-5% for NAFLD and NASH, respectively [1,2]. Driven primarily by lifestyle, obesity and type 2 diabetes, these figures are predicted to grow. Furthermore, NASH is already reported to be the fastest-growing cause of primary liver cancer and liver transplant in the USA.
Currently, the definitive diagnosis of NASH relies on a liver biopsy, which is also required by the FDA as the primary endpoint for late-stage NASH clinical trials. Although liver biopsy is currently the gold standard, it has well-reported limitations including not only pain, but also risk of complications from the procedure itself and errors in the measurement. Given the high and growing prevalence of NASH and the invasive nature of the procedure, liver biopsy is not a scalable solution to diagnose a large population of patients or routinely evaluate disease progression in participants throughout a clinical trial or in clinical practice. Safer and more patient-friendly alternatives to biopsy are needed both for higher clinical throughput and more effective clinical development. Such needs are further corroborated by critical multi-stakeholder initiatives such as the LITMUS [3,4] and NIMBLE  consortia, including interest from global regulatory agencies to support such goals toward a non-invasive approach to diagnose, monitor, and care for patients with NASH. However, to ensure that such non-invasive alternate measures are accurate and precise, they must be validated using liver biopsy results.
A potential alternative is LiverMultiScan, a non-invasive MRI-based technology that measures liver fibro-inflammation (using cT1) and fat (using PDFF) — both hallmark features of NASH. This recent study, published in Frontiers of Endocrinology, showed that in 264 patients with suspected NAFLD or NASH, cT1 and PDFF were both correlated with all features of the biopsy-based NAFLD activity score (NAS), including steatosis, inflammation and ballooning. Specifically, an estimated difference of 88 msec in cT1 or 21% relative difference in PDFF was related to a two-point difference in overall NAS. This evidence supports the potential utility of LiverMultiScan as a non-invasive and accurate test for evaluating changes in liver health in response to treatment. Notably, cT1 was independently associated with inflammation and fibrosis – pathological hallmarks that correlate the most to clinical outcomes - offering further advantage for use as a biomarker to monitor treatment response .
“Non-invasive tests have great promise as alternatives to liver biopsy for primary endpoints in late-stage NASH clinical trials, said Manu Chakravarthy, MD, PhD, one of the co-authors of the trial and Chief Medical Officer at Axcella Health. “As clinical researchers and drug developers, we are always looking for ways to improve the experience of our trial participants while collecting more robust data that will allow us to make informed decisions on efficacy and safety with a sight toward improved clinical outcomes. This study shows how one such test, LiverMultiScan, can accurately measure the hallmark disease characteristics of NASH using cT1 and PDFF that are correlated to histologically relevant endpoints, allowing us to reliably assess changes in disease state more frequently. Ultimately, emerging data such as these may enable a paradigm shift in the investigation and treatment of NASH to better understand an individual’s response to a given treatment throughout a clinical trial and in real-world practice.”
The results of this study show how LiverMultiScan could be a safer, more scalable alternative to liver biopsy. It has proven accuracy, strong correlation to histological changes, ability to detect early liver disease and predict clinical outcomes as demonstrated in a previous study . LiverMultiScan has the potential to enhance the screening, enrichment, and monitoring capabilities of sponsors running NASH clinical trials for improved patient welfare, reduced costs and accelerated drug development.
Read the full paper here.
2. Marcellin P, Kutala BK. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38(Suppl. 1):2–6. https://doi.org/10.1111/liv.13682
3. Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS). https://litmus-project.eu/
5. Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE). https://fnih.org/nimble