Biomarker Strategies for Significant and Advanced Liver Disease at the Primary and Secondary Healthcare Levels

Metabolic dysfunction-associated steatotic liver disease (MASLD), is a chronic, asymptomatic, progressive condition affecting about 38% of the global population. It is characterized by substantial interpatient variability in disease severity and outcomes. MASLD is caused by a build-up of fat in the liver and includes a range of disease states, from isolated lipid accumulation or steatosis (metabolic dysfunctionassociated steatotic liver, MASL) to its active inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH).

Some points should be noted while setting the goal for diagnostic tests for advanced liver disease at the primary and secondary healthcare levels, such as:

• In primary care, there is a low prevalence of advanced (F3-4) diseases. So, severe cases should be excluded.
• On the other hand, the prevalence of advanced disease is increasing in secondary care.
• Hence, it is important to identify patients with ≥F2 for therapy and monitoring.
• Patients with F(3)4 should be identified for intensive therapy and surveillance.

Diagnosis and identification of the patients at different stages of the disease can be done with the help of biomarkers, which can be categorized into two groups, i.e., indirect and direct serum biomarkers and imaging biomarkers.

For example, in the enhanced liver fibrosis (ELF) test in MASLD, three direct markers of fibrosis are combined, such as procollagen III N-terminal peptide, hyaluronic acid and tissue inhibitor of metaproteinase 1 (TIMP1).

Some other key biomarker strategies that can help in diagnosing are:

• At present, the staged application of available ‘simple panel’ biomarkers, such as NFS, and FIB-4 followed by noninvasive tests, such as fibroscan, ELF and MR elastography helps to rule out cases that are unlikely to have significant disease.
• The biomarker field is developing rapidly, therefore, the objective assessment of biomarker performance for specific predefined context of use is important to understand their utility.
• There is an urgent need for more sensitive and specific, independently validated, and qualified biomarkers for use in MAFLD.
• Promising experimental biomarkers, include direct biomarkers related to ECM turnover, metabolomic profiling and miRNAs. However, they all require further validation.