Evaluation of Cytokeratin 18 and Fibroblast Growth Factor-21 as Noninvasive Biomarkers of Severity in Nonalcoholic Fatty Liver Disease

Introduction: Nonalcoholic fatty liver disease (NAFLD) often remains asymptomatic until advanced stages and diagnosis with severity grading usually requires liver biopsy. There is an urgent need for reliable noninvasive biomarkers to differentiate disease severity. This study aimed to evaluate cytokeratin 18 (CK-18) and fibroblast growth factor-21 (FGF-21) as markers of NAFLD severity. Subjects and Methods: A hospital-based observational study was conducted at a tertiary care center in North India, enrolling 120 diagnosed NAFLD patients. All participants underwent fibroscan assessment of fibrosis (F0–F4). Serum CK-18 and FGF-21 were measured by the enzyme-linked immunosorbent assay. Median levels were compared across severity subgroups. Results: Serum CK-18 and FGF-21 levels correlated significantly with fibrosis severity. CK-18 levels in F1, F2, and F3 were 1.35 ng/ml, 1.89 ng/ml, and 4.4 ng/ml, respectively, while FGF-21 levels were 251 pg/ml, 268.6 pg/ml, and 502 pg/ml. CK-18, at an optimal cutoff of 1.74 ng/ml, showed the highest predictive value for severe fibrosis with an area under the ROC curve of 0.879. On multivariate analysis, CK-18 emerged as an independent marker for advanced fibrosis, even after adjusting for confounders. Conclusions: Serum CK-18 levels serve as a biomarker of severity of fibrosis in NAFLD and may be applied for noninvasive disease monitoring. Its role could extend to tracking disease progression and evaluating the effectiveness of lifestyle or therapeutic interventions, reducing the need for invasive liver biopsy.