Study Suggests Value of Noninvasive FibroScan-AST Score for Ruling Out Fibrotic MASH

New research is providing clinicians with an overview of the utility of the FibroScan-aspartate aminotransferase (AST) score for ruling in and ruling out fibrotic metabolic dysfunction-associated steatohepatitis (MASH).¹

Findings from the systematic review and meta-analysis of 16 studies comprising more than 8000 participants suggest the FAST score performs better for ruling out fibrotic MASH compared with ruling in the target condition, although a sequential testing approach implemented after a FAST ≥ 0.67 may be a viable strategy to ruling in fibrotic MASH.¹

On March 14, 2024, the US Food and Drug Administration granted accelerated approval to resmetirom (Rezdiffra) for the treatment of noncirrhotic MASH with moderate to advanced fibrosis, making it the first FDA-approved MASH therapeutic.² With various other agents in the MASH pipeline, clinical development efforts have been limited by barriers to trial enrollment.¹

“Due to stringent histological criteria for patient inclusion, MASH clinical trials have screening failure rates exceeding 70%,” Konstantinos Malandris, MD, of the clinical research and evidence-based medicine unit at Aristotle University of Thessaloniki in Greece, and colleagues wrote.¹ “To address this issue and to mitigate unnecessary liver biopsies, Newsome et al. developed a noninvasive index, the FAST score, providing cutoff values for ruling-in and ruling-out fibrotic MASH.”

Derived from a combination of controlled attenuation parameter, liver stiffness measurements (LSM) by vibration-controlled transient elastography, and AST levels, the FAST score was developed to facilitate the noninvasive identification of patients at risk of progressive MASH for clinical trials or treatments, reducing unnecessary liver biopsy in patients unlikely to have significant disease.³

To assess the diagnostic accuracy of the FAST score for fibrotic MASH based on available evidence, investigators searched Medline, Cochrane Library, Web of Science, and Scopus for relevant studies from the first publication of the FAST score on February 3, 2020, up to January 11, 2024. Studies were eligible for inclusion if they assessed the accuracy of FAST score for detecting fibrotic MASH, defined as MASH with a NAFLD activity score ≥ 4 and fibrosis stage ≥ F2, using biopsy as the reference standard at previously reported thresholds (FAST ≥ 0.67 for ruling in and ≤ 0.35 for ruling out fibrotic MASH).¹

Initial literature searches yielded 1626 records, 1215 of which were screened at the title and abstract level and 63 of which were assessed in full text. In total, 16 studies with 8838 participants meeting eligibility criteria were included in the systematic review and meta-analysis.¹

Investigators noted most studies were multicenter (n = 11) following a prospective design (n = 9) with a recruitment period spanning from 2003 to 2021. Across the included studies, the mean age was 52.5 years and 45.2% of participants were male.¹

Of the 8838 participants, 2913 (32.9%) had fibrotic MASH with prevalence ranging from 14.1% to 55.0%. The overall prevalence of cirrhosis and significant fibrosis was 8.1% and 45%, respectively. Investigators noted 2721 (30.8%) participants had a FAST score between 0.35 and 0.67, putting them in the gray zone.¹

In total, 15 studies with 8342 participants assessed the accuracy of the FAST score for ruling in fibrotic MASH, with sensitivity and specificity ranging from 0.09 to 0.73 and from 0.67 to 0.98, respectively. Upon analysis, a FAST score ≥ 0.67 yielded a pooled sensitivity of 0.45 (0.39 to 0.52) and specificity of 0.87 (0.82 to 0.90), resulting in a positive likelihood ratio of 3.6.¹

In total, 16 studies with 8507 participants provided data for the accuracy of the FAST score for ruling out fibrotic MASH, with sensitivity and specificity ranging from 0.52 to 1.00 and from 0.14 to 0.79, respectively. A FAST score ≤ 0.35 yielded a pooled sensitivity of 0.88 (0.83 to 0.91) and specificity of 0.52 (0.45 to 0.60), corresponding to a negative likelihood ratio of 0.23.¹

At a prevalence of 30%, investigators pointed out the positive predictive value for ruling in fibrotic MASH was 60% while the negative predictive value for ruling out the target condition was 91%.¹

For ruling in fibrotic MASH, the number of pathologists reviewing biopsy specimens (P = .03) and the prevalence of cirrhosis (P = .03) were identified as potential sources of heterogeneity. For ruling out fibrotic MASH, greater AST levels tended to improve sensitivity estimates (P = .04).¹

Investigators pointed out the certainty of the evidence for both outcomes was low to very low, largely attributable to concerns regarding the risk of bias and imprecision. Of note, 12 studies were at high risk or at some concern for bias due to patient selection and/or suboptimal reporting of the blinding status with respect to biopsy results during interpretation of FAST score.¹

Investigators recognized this bias as a limitation to the study’s findings, also mentioning the heterogeneity among included studies; the limited number of studies included in the analysis; and the potential for overlap between cohorts included in the primary studies.¹

“Based on low to very low certainty of evidence, FAST score seems to perform better for ruling out fibrotic MASH compared with ruling in the target condition,” investigators concluded.¹ “FAST's low PPV even in high prevalence settings necessitates sequential testing for ruling in fibrotic MASH. Individual FAST components (especially LSM) should be taken into account when interpreting results even when aiming to rule out fibrotic MASH.”

References

1. ^{Malandris K, Arampidis D, Mainou M, et al. FibroScan-AST score for diagnosing fibrotic MASH: A systematic review and meta-analysis of diagnostic test accuracy studies. JGH. https://doi.org/10.1111/jgh.16770}
2. ^{Brooks, A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed October 15, 2024. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash}
3. ^{Newsome PN, Sasso M, Deeks JJ, et al. FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol. doi:10.1016/S2468-1253(19)30383-8.}