TABLE 2.

Roadmap for discovery and validation of candidate biomarkers in AIH

	Discovery	Confirmation	Validation	Regulatory approval
Key Properties	Biologically plausible Noninvasive or from peripheral blood Correlation with clinical markers (ALT, IgG, histology) and disease state	Assay optimization, standard operating procedure (SOP)	Acceptable interassay variability	Utility in point‐of‐care testing Cost‐efficient and reproducible at routine clinical labs
Testing Setting	Single site/lab	Two/Three site/lab Transferability of assays	Multicenter, international sites/labs	Regulatory Agencies (EMA, FDA) Biomarker qualification process
Clinical Dataset for Correlation	Retrospective	Retrospective, Prospective	Prospective	Prospective Patient Registry
Outcome	Sensitivity and Specificity	Reliability	Sensitivity and Specificity	Correlation with relevant clinical outcomes
Theoretical Application to AIH	Metabolite of hepatic T cell activity measured in peripheral blood in adults with AIH	Metabolite accurately indicates histological activity despite normal ALT while on IST	Metabolite predicts relapse in adults and children with AIH	Metabolite is a biomarker of disease response to IST and can serve as a measurable datapoint in clinical trials

Abbreviations: AIH, autoimmune hepatitis; ALT, alanine aminotransferase; EMA, European Medicines Agency; FDA, Food and Drug Administration; IgG, immunoglobulin G; IST, immunosuppressive treatment.