Biomarkers of liver fibrosis: what lies beneath the receiver operating characteristic curve?

Noninvasive biomarkers of liver fibrosis represent an intense area of research with the goals of improving patient care, disease stratification, and aiding the development of future antifibrotic therapies. Despite the rapid progress in recent years, there remain questions about how diagnostic studies are designed, statistical methods to account for spectrum bias, clinically relevant thresholds of fibrosis that should be delineated, how diagnostics can be improved, and strengthening the reference test to judge emerging biomarkers. This review discusses the current methods to address these issues and where further progress is needed.