Abstract
BACKGROUND: Activation of hepatic stellate cells (HSCs) in response to liver injury increases extracellular matrix (ECM) deposition and upregulation of tissue inhibitor of metalloproteinase-2 (TIMP-2), promoting fibrogenesis, a key feature of metabolic dysfunction-associated fatty liver disease (MAFLD). This study was conducted to determine the diagnostic potential of serum TIMP-2 levels in patients with MAFLD/nonalcoholic fatty liver disease (NAFLD). METHODS: This case-control study included 100 MAFLD patients and 100 healthy controls. Demographic profiling, ultrasonography, and FibroScan with controlled attenuation parameter (CAP) scoring were conducted. Serum TIMP-2 was quantified using enzyme-linked immunosorbent assay (ELISA), and routine biochemical parameters (liver function test, kidney function test, fasting plasma glucose, postprandial blood sugar, HbA1c, total cholesterol, triglycerides, and GGT) were assessed using fully automated chemistry analyzers. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic utility of TIMP-2. RESULTS: Serum TIMP-2 levels were significantly higher in MAFLD patients (p < 0.001) compared with controls. Serum TIMP-2 showed a significant positive correlation with ALT (rho = 0.569, p < 0.001), GGT (rho = 0.551, p < 0.001), fasting plasma insulin (rho = 0.562, p < 0.001), and FibroScan scores (r = 0.560, p < 0.001). ROC analysis yielded an AUC of 0.933 (95% CI: 0.889-0.963) with a TIMP-2 cut-off value of 8.909, showing a sensitivity of 91% and specificity of 99%. CONCLUSION: Serum TIMP-2 levels are significantly elevated in MAFLD and show strong correlations with liver enzymes and CAP scores, suggesting a relationship with hepatic fat accumulation and liver injury. Additionally, associations with lipid levels, white blood cell count, and neutrophils imply a link to systemic inflammation and liver fibrosis, highlighting the promising role of TIMP-2 as a noninvasive, blood-based biomarker for early detection and monitoring of liver fibrosis. Further studies are needed to substantiate the diagnostic potential of serum TIMP-2 in MAFLD patients.