Non-Alcoholic SteatoHepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD), which is characterised by inflammation and liver damage, including various stages of fibrosis.
NASH is massively under-diagnosed, partly because it is a silent disease with few, often-mild symptoms and partly because definitive diagnosis is by histopathology of a liver biopsy which the treating physician or patient may prefer not to perform and/or provide. Additionally, a liver biopsy will not represent the whole liver and it is critical to obtain as sizeable a specimen as possible.
The risk of performing a liver biopsy is therefore a hurdle for enrolment in many NASH studies. This is compounded by the current absence of approved therapies and thus the enticements to encourage patients to undergo a liver biopsy are currently comparatively limited.
Several groups are trying to address this by creating clinical diagnostic tools, including imaging solutions, that are less invasive and of comparable clinical accuracy thus eliminating the need for a liver biopsy. Other strategies include the use of non-invasive tools to pre-screen subjects to better predict those that are least likely to be suitable for the enrolment requirements of a clinical study and therefore should not proceed to a biopsy.
Another challenge that impacts site engagement and, consequently, enrolment rates is the analysis of the liver biopsy and the differences in assessments performed by the local pathologist and the central specialist pathologist. Improving communication between the local pathologist, investigator and the central pathologists is crucial to ensure uniformity of the study population and the consistency of assessment throughout the study.
ICON provides an extensive range of clinical research solutions, along with deep therapeutic area expertise to help you gain insights into the complexities of NASH. We are working to expand our network of NASH qualified clinicians and sites by helping them link up with specialists with the appropriate skills and equipment (e.g. MR imaging, radiologist for biopsies and Fibroscan to measure liver stiffness) as a means of optimising enrolment. To speak to one of our experts, please contact us.
This blog is an edited version of “NASH Clinical Trials: An Outlook on Challenges and Advances” which appeared in the Cardiometabolic Chronicle in October 2019, Vol. 2 Q4. To view the full article, please visit https://www.cardiometabolichealth.org.