Clinical value of serum PIIINP in liver fibrosis staging and establishment of a rapid time‑resolved fluorescence lateral flow assay

This study aimed to evaluate the clinical diagnostic performance of serum procollagen type III N‑terminal propeptide (PIIINP) for staging liver fibrosis, and to establish a time‑resolved fluorescence lateral flow assay (TRF‑LFA) for its rapid quantitative detection. This study consisted of two parts. Part 1 evaluated the diagnostic performance of PIIINP alone and in combination with HA, LN, and IV‑C for fibrosis staging (Scheuer ≥ S2 and ≥ S3) using CLIA in 486 patients. Part 2 developed and validated a Eu 3 ⁺‑labeled TRF‑LFA for PIIINP detection, assessing linear range, limit of detection, precision, and spike recovery, and compared its qualitative concordance with CLIA in 55 biopsy‑confirmed samples using 2 × 2 tables and Cohen ‘s kappa. In the diagnostic cohort, single PIIINP yielded AUC values of 0.781 for identifying significant fibrosis (Scheuer ≥ S2) and 0.857 for advanced fibrosis (Scheuer ≥ S3). Incorporating HA, LN, and IV‑C into the model increased these values to 0.852 and 0.930, respectively. For the analytical performance of the TRF‑LFA, the limit of detection was 4 ng/mL, with a linear range of 5–1000 ng/mL. The intra‑assay and inter‑assay coefficients of variation ranged from 1.85 to 2.34% and 3.38 to 4.27%, respectively. The overall mean matrix spike recovery reached 102.69%. Using each method’s respective reference interval as the qualitative cut-off, the overall concordance between TRF‑LFA and CLIA reached 90.91% (κ = 0.74, 95% CI: 0.53–0.96). Serum PIIINP is a reliable auxiliary biomarker for Scheuer‑based liver fibrosis staging, and its combination with HA, LN, and IV‑C further enhances diagnostic performance. The TRF‑LFA enables rapid and quantitative point‑of‑care testing (POCT) of PIIINP within 15 min, making it well‑suited for use in primary care and resource‑limited settings.