Non-Invasive Test Developed for NASH and Liver Fibrosis

Researchers in the UK have created a highly accurate, sensitive and specific liquid biopsy test for major liver diseases non-alcoholic steato-hepatitis (NASH) and liver fibrosis. The test also allows for doctors to determine the staging of both diseases without the need for invasive liver biopsies.

NASH is the most severe form of non-alcoholic fatty liver disease (NAFLD) and is diagnosed in approximately 60% of NAFLD patients. NASH puts people at risk of progressing to advanced liver diseases such as liver fibrosis, cirrhosis, and liver cancer. NAFLD affects approximately 52 million people in Europe and 64 million people in the US, costing $138 billion annually to the European and US healthcare systems combined.

Currently, NASH can only be diagnosed through liver biopsy, which is the standard of diagnosis but is invasive, expensive, and has co-morbidities and complications. There are also no reliable blood (i.e., liquid biopsy) tests for these diseases because of low sensitivity and specificity. Current blood tests are also unable to reliably predict NASH and fibrosis staging.

The new test is based on two protein biomarkers, PLIN2 and RAB14, that were used as part of algorithms to identify people with NASH and/or liver fibrosis. Professor Geltrude Mingrone, from King’s College London and Catholic University of Rome, Italy, and colleagues evaluated the ability for these proteins to detect NASH was tested in cohorts of people with either biopsy-confirmed NASH or liver fibrosis.

The algorithms, which are based on artificial intelligence and described in more detail in the journal Gut, gave favorable results, including sensitivity of 88-95%, specificity of 90%-100%, and overall accuracy of 92-93% for NASH. For fibrosis, the results were even better, with sensitivity of 99%-100%, specificity of 90%-96%, and accuracy of 98%-99%. This is much more accurate than all other currently available biomarkers.

"This blood test will allow to define the real prevalence of NASH in large and small populations, including children and adolescents, avoiding the need for invasive liver biopsy,” says Mingrone. “Importantly, it will also allow to monitor the efficacy of NASH treatments over time, reducing screen failures and helping generate better drugs."

These results show that the PLIN2/RAB14-based liquid biopsy can provide rapid and cost-effective testing to combat the growing epidemic of NASH and liver fibrosis. This will be an invaluable tool in diagnosing and monitoring cases of liver diseases, enabling people to receive earlier treatment.

The authors also believe that the testing will allow for the improved capacity for researchers to study NASH and liver fibrosis in the general population, including disease progression, and record the effects of treatment, from lifestyle to surgical and pharmacological interventions. No NASH drug has been approved by the FDA or EMA due to the lack of an accurate, reliable, and non-invasive test. Between 65-73% of patients that currently enroll in clinical trials for NASH-related therapies are found to be ineligible for the trial due to screen failure.

The test, which was developed in collaboration with Metadeq Corp., is expected to significantly reduce screen failures in clinical trials and improve the chances of new life-saving drugs reaching the market.