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Non-invasive tests for metabolic dysfunction-associated steatohepatitis (MASH) may be a viable option for screening those at risk and avoiding unnecessary invasive testing, according to a study published in Liver International.¹

Clinical trials investigating drug therapy for MASH currently use invasive liver tissue sampling to determine MASH and staging of fibrosis in order to select histologically eligible study participants. 

鈥淲e have found that liver stiffness measurements combined with blood-based markers could reduce the proportion of potential participants by up to 80%,鈥� the researchers reported. 鈥淪uch performance could decrease the costs related to running clinical trials and thus accelerate drug development.鈥�¹

Because screen failure rates (SFRs) can be high when patients undergo biopsy during this recruitment process, non-invasive screening tests (NITs) could help to identify patients who are more likely to fulfill clinical trial eligibility criteria based on histology. NITs have been largely investigated as risk stratification tools in clinical practice, in which the primary goal is to circumvent liver biopsies (when possible), chiefly among individuals with low NIT scores and a low likelihood of clinically relevant liver fibrosis.

An international research team therefore sought to explore the utility of NITs as a screening component in MASH clinical trials for identifying appropriate patients for biopsy before study inclusion. These researchers previously performed a large individual participant data meta-analysis (IPDMA) to evaluate the diagnostic accuracy of NITs.²

For their most recent study they used the IPDMA data set to assess if widely accessible NITs could be applied in screening approaches to decrease the SFR in MASH clinical trials. 

Analyzing NIT utility

The performance of single NITs as well as sequential application of NITs were assessed in the IPDMA using data obtained from 2281 participants for whom FAST, FIB-4, and NFS could be calculated. Median age of the study cohort was 55 years; 50% of study participants were women, 49% had diabetes, and 38% had BMI 鈮�30 kg/m². 

The research team considered MASH plus significant fibrosis (F2-F4), or 鈥渁t-risk鈥� MASH, as the primary target condition. In other words, the primary aim was to assess the diagnostic performance of NITs as a screening tool for MASH plus F2-4 in which individuals with NIT values above a defined threshold were chosen to undergo biopsies. Secondary target conditions included MASH plus F2-3, MASH plus F4, F2-F4, and MASH. 

Index NITs included:

• FibroScan-AST (FAST) score
• Liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE)
• Fibrosis-4 score (FIB-4)
• Non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS)

The research team reported on area under the empirical receiver operating characteristic curves (AUROCs) and thresholds including those that yielded 34% SFR. 

Reducing resource utilization

As the authors pointed out in their report, the primary finding was that the diagnostic performance of simple NITs, like NFS or FIB-4, followed by LSM-VCTE or FAST was similar to that of LSM-VCTE or FAST alone as screening approaches for MASH plus F2-4.

The authors concluded from this observation, 鈥淪equential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.鈥� They added that sequential combinations of NITs may also reduce SFRs and the number of individuals who require biopsies.

Prevalence of MASH plus F2-4, MASH plus F2-3 and MASH plus F4 was 31%, 24% and 7%, respectively, reflecting that SFRs would be 69%, 76%, and 93%, respectively, if no initial screening was done. 

The research team calculated AUROCs, as a measure of diagnostic performance, to be:

• 0.78, 0.75, 0.68, and 0.57 for FAST, LSM-VCTE, FIB-4, and NFS, respectively, regarding MASH plus F2-4. 
• 0.73, 0.67, 0.60, and 0.58 for FAST, LSM-VCTE, FIB-4, and NFS, respectively, regarding MASH plus F2-3. 
• 0.79, 0.84, 0.81, and 0.76 for FAST, LSM-VCTE, FIB-4, and NFS, respectively, regarding MASH plus F4. 

The authors also pointed out that only small decreases in SFR could be obtained when NITs were applied as screening measures for MASH plus F2-3 or MASH plus F4. But, at the same time, fewer biopsies would need to be conducted. They emphasized 2 examples to illustrate this observation. 

First, as mentioned, the prevalence of MASH plus F2-3 was 24%. FAST cut-offs of 0.35 and 0.67 for choosing individuals for biopsy decreased the SFR from 76% to 72% and led to liver biopsies in only 35% of participants. Similarly, the prevalence of MASH plus F4 was 7% and applying a LSM-VCTE threshold of >10kPa for selecting individuals to undergo biopsies decreased the SFR from 93% to 84% and led to liver biopsies in only 36% of participants. 

鈥淪creening with NITs to identify patients at high risk of MASH+F2-3 and MASH+F4,鈥� the authors concluded, 鈥渃an lead to modest gains in SFR and sizeable reductions in the number of biopsies that need to be performed, a strategy that can carry favourable cost implications.鈥� 

Limitations of this study include a single data set from the U.S. and Australia, and possible analysis bias due to overlapping data with the study from which the FAST score was derived.³ Additionally, the investigators were unable to account for changes in the practice and use of NIT strategies occurring over the 10-year study period.

Published: May 15, 2024