Q&A: FAST score, other noninvasive tests help identify, stratify at-risk MASH patients

Key takeaways:

• Researchers recommended the FibroScan-AST score to target those at risk for MASH.
• The score should be used with a cutoff point of 0.5 when HbA1c is at least 6.5% and 0.67 when HbA1c is less than 6.5%.

BOSTON — Researchers recommended the FibroScan-aspartate aminotransferase score as a noninvasive biomarker to stratify patients at risk for metabolic dysfunction-associated steatohepatitis, when used with different cutoff points for HbA1C.

“MASH represents a major economic burden on the worldwide health care systems and a high unmet medical need as there is no approved therapy yet,” Stephen A. Harrison, MD, FAASLD, founder of Pinnacle Clinical Research in San Antonio, told Healio. “At-risk MASH patients, defined as patients with MASH and moderate to significant fibrosis, have a high risk of comorbidity and mortality.”

To investigate the main predictors of at-risk MASH, Harrison and colleagues used screening data from seven phase 2 MASH trials and included 2,173 patients with centrally assessed liver biopsies, of whom 42% met histopathological criteria for at-risk MASH.

Here, Harrison breaks down the key results, which were presented at the Liver Meeting, and how they might inform patient care going forward.

Healio: Why did your team undertake this investigation?

Harrison: The current diagnostic gold standard is liver biopsy, which is also being used as a surrogate endpoint for conditional approval of drug candidates. However, this invasive procedure carries substantial variability in its assessment resulting in major hurdles in clinical trials, including but not limited to increased screen failure rate, study duration and cost.

Approximately 60% of patients having a liver biopsy in clinical trials are deemed ineligible. Thus, there is a need to enrich the population screened for clinical trials with patients presenting with a higher likelihood of disease. We were able to collect data from several clinical trials with the aim to identify the main predictors of at-risk MASH patients. We also assessed the performance of existing noninvasive tests for the stratification of at-risk MASH patients.

Healio: What were the most notable takeaways?

Harrison: The enrichment with a more severe population in clinical trials can be achieved by using simple noninvasive tests such as liver chemistry tests, HbA1c and transient elastography. AST, Fibrosis-4 (FIB-4), HbA1c, transient elastography and its derived score, FibroScan-AST (FAST), can be used to stratify at-risk MASH patients.

However, none of those tests exhibit excellent diagnostic accuracy and their respective cutoffs points seem to be significantly impacted by the level of glucose control as assessed by HbA1c. Consequently, we recommend using those noninvasive tests with different cutoff points according to glucose control.

For example, enrichment of the population in clinical trials could be achieved by using the FAST score — a combination of liver chemistry tests and transient elastography — with a cutoff point of 0.5 for patients with HbA1c of 6.5% or higher and 0.67 for patients with HbA1c below 6.5%.

Healio: How might these results inform patient care going forward?

Harrison: This study complements the body of evidence on noninvasive tests to stratify at-risk MASH patients and suggests that some of those tests, such as FIB-4, used in the current scientific guidelines may benefit from refinement in order to adapt their respective cutoff points according to glucose control.

Those simple noninvasive tools can be used to target at-risk MASH patients for specialists’ referral for further management.

Healio: What additional research is needed?

Harrison: There is a body of evidence on the diagnostic accuracy of several noninvasive tests to stratify at-risk MASH. However, none of them exhibit excellent accuracy. Further research is warranted to find better biomarkers.

The field would benefit significantly from the use of noninvasive tests instead of liver biopsy for regulatory approval but also for patients’ standard of care as this is unlikely that, when a drug will be approved, the health care systems can support the use of liver biopsy to define treatment indication.

Further research assessing the accuracy of these noninvasive biomarkers to predict major adverse liver outcomes and response to treatment is also of paramount importance to support their endorsement by all stakeholders.