Systematic review of performance of non‐invasive biomarkers in the evaluation of non‐alcoholic fatty liver disease

This systematic review evaluates the many studies carried out to discover and evaluate non‐invasive markers of non‐alcoholic fatty liver disease (NAFLD). Many different strategies and methods have been used in this task, from the discovery of new markers by global ‘shotgun’ studies to hypothesis‐driven approaches, to the development of algorithm tests based on routinely available clinical and biochemical parameters. We examined the various different approaches, summarising the findings in an attempt to give an overview of the field of non‐invasive markers in NAFLD, encompassing markers of steatosis, necro‐inflammation and fibrosis. The body of literature surrounding this topic is complex and varied, encompassing not only different methodologies but also different patient characteristics, different disease definitions, as well as different end points. This reflects the heterogeneity of NAFLD, which, however, introduces considerably difficulty when trying to draw a conclusion between studies. We have divided this review into three main chapters based on the characteristics of the studies. The Genomics/Proteomics chapter reviews studies using a non‐hypothesis‐driven approach to biomarker discovery. Thereafter, we evaluate studies of association – studies that target‐specific markers, comparing levels between disease and control groups. Finally, we examine the algorithm tests – mathematical systems developed on the basis of previously described markers and assessed, usually, by receiver operator curve analysis. While radiological examination and investigations offer important diagnostic information, such studies are not discussed in this review – the body of literature surrounding blood and anthropological markers is complex and varied, demanding close attention.