The “Perfect” NASH Biomarker: An Unrealistic Pursuit?

Seeking the perfect NASH biomarker may be unrealistic; versatility is key. A diverse biomarker pool adapts to varied clinical contexts and settings. FIB-4, a cost-effective marker, can be supplemented by complex multimarkers for NASH therapeutic trials. Embracing diagnostic imperfections is crucial for flexible biomarker algorithms.
PUBLISHED IN: Lancet Gastroenterol Hepatol 2023


The rise of obesity and type 2 diabetes during the past 20 years has been accompanied by an increase in their associated multiorgan impairments. Non-alcoholic fatty liver disease (NAFLD) is one such complication. As a complex multisystem disease, it is characterised by fibrosis as well as cross-talk between the liver and extrahepatic organs, thereby heightening the risk of adverse clinical outcomes.

However, only a small proportion of NAFLD patients progress to non-alcoholic steatohepatitis (NASH) or advanced liver fibrosis, two clinically relevant endpoints with the highest risk of adverse liver-associated events. To identify these at-risk patients, a plethora of studies have attempted to discover the ideal NASH biomarker.

This study aimed to critically assess the purpose of quests for the perfect NASH biomarker at the expense of biomarker versatility. 

Key learnings:

Although the discovery of a perfect biomarker able to identify all four histological components of NASH is promising, it may be more realistic to remain versatile. Under current epidemiological circumstances, gastrohepatologists may benefit from establishing a widely available biomarker pool able to be adapted to disparate clinical contexts and settings.

FIB-4 is a cheap and straightforward NASH biomarker that may represent a balance during wider case-finding efforts, and its efficacy may be supplemented by more expensive and complex multimarkers when identifying patients for inclusion in NASH therapeutic trials.

Maintaining a balanced perspective which is both versatile and mindful of the diagnostic imperfections of liver histology as well as the rising burden of NAFLD is thus of paramount importance to establishing flexible biomarker algorithms.

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S Duarte, BSc

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