Factors Associated With Liver Fibrosis in Patients With Type 2 Diabetes and the Predictive Value of CHI3L1

ABSTRACT Aims Among individuals with type 2 diabetes mellitus (T2DM), the prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) is disproportionately high, contributing to increased vulnerability toward cirrhosis and, ultimately, primary liver cancer. Early identification of hepatic fibrosis in such patients is therefore of paramount importance. We aimed to explore clinical determinants of fibrosis in patients with T2DM and MASLD and examine chitinase‐3‐like protein 1 (CHI3L1) as a potential indicator of fibrotic progression. Methods This retrospective study included patients with T2DM who initially visited Tianjin Third Central Hospital (January 2023–August 2024). Liver fibrosis was assessed both across the entire T2DM cohort and among those with coexisting MASLD, based on liver stiffness measurement (LSM) and noninvasive indicators, such as aspartate aminotransferase‐to‐platelet ratio index (APRI), fibrosis‐4 (FIB‐4) index, and CHI3L1. An LSM threshold of 8 kPa was used to identify significant liver fibrosis (SLF). Associations between LSM, CHI3L1, and other indicators were examined by correlation analysis. Risk factors of liver fibrosis were determined by logistic regression analyses, and the discriminative ability of CHI3L1 was evaluated using receiver operating characteristic curve analysis. Results The cohort comprised 236 patients with T2DM, including 176 with concomitant MASLD (74.6%) and 89 with SLF (37.7%). In the T2DM–MASLD group, 74 (42.0%) patients had SLF, with significantly elevated weight, body mass index (BMI), thyroid‐stimulating hormone (TSH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), FIB‐4, CHI3L1, APRI, LSM, and controlled attenuation parameter (CAP), and reduced systolic blood pressure (SBP), platelet count (PLT), low‐density lipoprotein cholesterol (LDL‐C), and platelet‐to‐white blood cell ratio (PWR), compared with their fibrosis‐free counterparts (all p < 0.05). A significant positive correlation was observed between CHI3L1 expression and LSM ( r = 0.48, p < 0.001). Multivariate analysis identified CHI3L1 (odds ratio [OR] = 1.84, 95% confidence interval [CI]: 1.209–2.809, p = 0.004), APRI (OR = 2.71, 95% CI: 1.629–4.529, p < 0.001), and CAP (OR = 2.63, 95% CI: 1.612–4.317, p < 0.001) as independent determinants of fibrosis risk. The predictive capacity of CHI3L1 showed an area under the curve (AUC) of 0.717 (95% CI: 0.638–0.796, p < 0.05), corresponding to a cutoff value of 96.6 ng/mL. Conclusion A substantial share of patients with T2DM were diagnosed with MASLD, while some had SLF. Patients with fibrosis had higher BMI, CHI3L1, AST, LDH, TSH, APRI, LSM, and CAP levels than those without. Notably, serum CHI3L1 correlated significantly with fibrosis and may function as a biomarker for disease progression.