Introduction: Metabolic-associated fatty liver disease is common, with fibrosis the major determinant of adverse outcomes. Population-based screening tools with high diagnostic accuracy for the staging of fibrosis are lacking.

Methods: Three independent cohorts, 2 with both liver biopsy and liver stiffness measurements (LSMs,≥F2) and advanced (≥F3) fibrosis.

Results: In the hospital-based cohorts, the N-terminal propeptide of type 3 collagen (Pro-C3) increased with fibrosis stage (P < 0.0001) and independently associated with advanced fibrosis (odds

Discussion: PRO-C3 and ADAPT reliably exclude advanced fibrosis in low-risk populations. The serial combination of ADAPT with LSM has high diagnostic accuracy with a low requirement for liver biopsy. The proposed algorithm would help stratify those who need biopsies and narrow down those patients who would need to be referred to specialty clinics.

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