Value of a Two-Step Approach with Cytokeratin-18 and Controlled Attenuation Parameter in Noninvasive Differential Diagnosis of Nonalcoholic Steatohepatitis

OBJECTIVE:To investigate the value of a two-step approach with cytokeratin-18 (CK-18) and controlled attenuation parameter (CAP) in the noninvasive diagnosis of nonalcoholic steatohepatitis (NASH).METHODS:A total of 65 patients with biopsy-proven nonalcoholic fatty liver disease were enrolled, including 30 patients with NASH. The M30 and M65 enzyme-linked immunosorbent assay kits were used to measure serum CK-18, and FibroScan was used to measure CAP. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUROC) was used to determine the value of noninvasive diagnosis. The binary logistic regression model was used to calculate the predicted probability of combined diagnosis. The maximum Youden index, a sensitivity of >90%, and a specificity of > 90% were used to determine the optimal cut-off value, the low value, and the high value, respectively.RESULTS:The results of the multivariate analysis showed that M65 (OR = 1.004, 95% CI 1.002-1.007, P = 0.003) and CAP (OR = 1.017, 95% CI 1.001-1.033, P = 0.036) were independent predictors of NASH. The AUROC of M65+CAP was 0.851 (95% CI 0.761-0.942), higher than 0.808 (95% CI 0.702-0.913) of M65 and 0.677 (95% CI 0.545-0.808) of CAP alone. A two-step approach with high (820.8 U/L) and low (527.7 U/L) values for M65 and the optimal cut-off value (293.5 dB/m) for CAP was used for the differential diagnosis of NASH, with a positive predictive value of 85.7%, a negative predictive value of 100%, and a coincidence rate of 92.0%.CONCLUSION:A two-step approach with M65 and CAP can improve the value of noninvasive diagnosis of NASH, and a high negative predictive value can avoid unnecessary liver biopsy.