Association of Serum Chitinase-3-Like Protein 1 with Liver Fibrosis Severity in Autoimmune Liver Diseases

Autoimmune liver diseases (AILDs) require precise fibrosis staging, but current non-invasive tools are limited. This study aimed to evaluate the diagnostic performance of serum chitinase-3-like protein 1 (CHI3L1) for liver fibrosis in AILDs.

This retrospective cohort study consecutively enrolled 226 AILDs patients (including those with autoimmune hepatitis, primary biliary cholangitis, and overlap syndrome) and 40 healthy controls. Cohort 1 (n=112) underwent liver biopsy (Scheuer staging). Cohort 2 (n=114) underwent liver stiffness measurement (LSM) by transient elastography, with no overlap between cohorts. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis and compared with aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4). Multivariable binary logistic regression adjusted for histological inflammation identified independent predictors of advanced fibrosis.

Serum CHI3L1 levels increased significantly with advancing histological (S0-1: 50.6 ng/mL; S2: 80.8 ng/mL; S3-4: 156.3 ng/mL; P < 0.001) and LSM-based fibrosis stages (F0-1: 57.8 ng/mL; F2: 70.9 ng/mL; F3-4: 164.5 ng/mL; P < 0.001). CHI3L1 was significantly correlated with APRI (r = 0.451), FIB-4 (r = 0.511), and LSM (r = 0.671). For diagnosing significant fibrosis (S≥2) and advanced fibrosis (S≥3), CHI3L1 showed areas under the ROC curve (AUC) of 0.833 and 0.851, respectively, performing comparably to FIB-4 and better than APRI. In the LSM cohort, CHI3L1 maintained high diagnostic accuracy (AUC: 0.828 for F≥2, 0.835 for F≥3). Multivariate analysis confirmed serum CHI3L1 is independently associated with advanced liver fibrosis.

CHI3L1 level is independently associated with advanced liver fibrosis and shows good diagnostic performance for both significant and advanced liver fibrosis. It is a valuable non-invasive biomarker to supplement existing fibrosis assessment strategies, pending validation across individual AILDs subtypes.