Among patients with non-alcoholic fatty liver disease (NAFLD), the assessment for the presence of non-alcoholic steatohepatitis (NASH) as well as the degree of fibrosis is clinically relevant as it guides prognosis, need for treatment, monitoring and influences eligibility for clinical trials. Unfortunately despite significant endeavours, there is currently a lack of accurate and validated biomarkers for determining NASH. This may in part be due to differing histological definitions of NASH and variability in pathologist interpretation and sampling error, leading to difficulty in establishing a ‘gold’ reference standard. Nonetheless, hypothesis free approaches using omics technology have identified a number of potential serum biomarkers including thrombospondin-2, which has also been shown to be predictive of clinical outcomes. Preliminary data also suggests imaging technologies including sonographic and magnetic resonance may be able to identify NASH. Further wide-spread validation of potential NASH biomarkers is required.

Non-invasive markers of fibrosis have been widely validated in NAFLD and are incorporated into clinical practice. Recent data has highlighted that combining serum markers (eg FIB-4) with vibration controlled transient elastography increases diagnostic accuracy and clinical utility. New serum markers quantifying neo-epitopes of pro-peptides formed during fibrinogenesis by cleavage of pro-collagen, have now been validated as accurate biomarkers in several cohorts of NAFLD patients. PRO-C3 is one candidate biomarker whose accuracy is further increased when combined with other covariates (eg age, diabetes, platelet count in the ADAPT score). Data for elastography techniques including point-sheer wave and 2-dimensional sheer wave elastography is increasing however diagnostic cut-offs require greater validation.