NOVEL non-invasive liver disease assessments (NILDAs) are effective alternatives to liver biopsy for fibrosis assessment in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), a 2026 systematic review has found.
Diagnostic Techniques in Liver Fibrosis
Established NILDAs include the Fibrosis 4 (FIB-4) index, aspartate platelet ratio index, and liver stiffness measurement (LSM) by transient elastography (TE) and magnetic resonance elastography (MRE). Researchers found that they are limited by indeterminate ranges and variable performance across different patient demographics.
The review analysed more than 900 records from 2020 to 2025, 48 of which met the inclusion criteria, and a further 15 of which were tests omitted from recent American Association of the Study of Liver Disease (AASLD) guidelines supporting the use of NILDAs for liver fibrosis diagnosis.
Novel NILDAs
Of the 15 novel NILDAs analysed, several had good to excellent discrimination. These findings established that novel NILDAs can be used in place of liver biopsy for fibrosis assessment.
The AASLD guidelines suggested combining blood-based and imaging-based NILDAs for fibrosis identification. Patients with MASLD who have a FIB-4 index of at least 1.3 should undergo further evaluation with an imaging-based NILDA. Traditionally, this is done with LSM by TE or MRE.
Future Treatment
The systematic review suggested that novel NILDAs Agile 3+ and Agile 4 are used in place of LSM alone, for advanced fibrosis and cirrhosis respectively.
Agile 3+ and Agile 4 scores were initially developed for use in secondary and tertiary hepatology clinics, to identify patients with MASLD and advanced fibrosis and cirrhosis, respectively. They use indicators including LSM, platelet count, sex, and diabetes.
Advantages of Novel NILDA Use
The use of FIB-4 followed by Agile 3+ or Agile 4 can predict advanced fibrosis or cirrhosis, whilst also reducing rates of indeterminate results.
The Agile scores performed similarly to LSM by TE but gave fewer indeterminate results and improved accuracy in classification when used in conjunction with FIB-4.
Potential Limitations
There are, however, questions surrounding accessibility and cost-effectiveness. For example, some novel NILDAs (excluding Agile 3+ and Agile 4) include biomarkers that are not widely accessible.
Although, many utilise basic information such as demographic data, BMI and diabetes status, potentially giving traction to the prospect of home-based NILDAs.
Clinical Application
The review found that scores such as FIB-4 and TE might be optimal to screen for those who do not have advanced fibrosis. Whereas, novel NILDAs may be advantageous in better predicting who do have advanced fibrosis.
There is also scope for AI to aid the development of NILDAs, but further research is needed.
Reference
Grady JT et al. Novel Noninvasive Tests for Liver Fibrosis: Moving Beyond Simple Tests in Metabolic Dysfunction-associated Steatotic Liver Disease. Clin Gastroenterol Hepatol. 2026;24(2):342-54.
