Cytokeratin 18, alanine aminotransferase, platelets and triglycerides predict the presence of nonalcoholic steatohepatitis

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the critical public health problems in China. The full spectrum of the disease ranges from simple steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma(HCC). The infiltration of inflammatory cells characterizes NASH. This characteristic contributes to the progression of hepatitis, fibrosis, cirrhosis, and HCC. Therefore, distinguishing NASH from NAFLD is crucial.

Objective and methods: Ninety-five patients with NAFLD, 44 with NASH, and 51 with non-NASH were included in the study to develop a new scoring system for differentiating NASH from NAFLD. Data on clinical and biological characteristics, as well as blood information, were obtained. Cytokeratin-18 (CK-18) fragments levels were measured using an enzyme-linked immunosorbant assay.

Results: Several indexes show significant differences between the two groups, which include body mass index (BMI), waist-on-hip ratio (WHR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), platelets, uric acid (UA), hs-C-reactive protein (hs-CRP), triglycerides (TG), albumin (ALB), and CK-18 fragments (all P < 0.05). The CK-18 fragment levels showed a significant positive correlation with steatosis severity, ballooning, lobular inflammation, and fibrosis stage (all P < 0.05). Therefore, a new model that combines ALT, platelets, CK-18 fragments, and TG was established by logistic regression among NAFLD patients. The AUROC curve in predicting NASH was 0.920 (95% CI: 0.866 - 0.974, cutoff value = 0.361, sensitivity = 89%, specificity = 86%, positive predictive value = 89%, negative predictive value = 89%).

Conclusion: The novel scoring system may be considered as a useful model in predicting the presence of NASH in NAFLD patients.

Figure 1. CK-18 fragments are significantly higher in the serum with NASH compared to patients with non-NASH.

The vertical axis represents serum CK-18 levels in U/L, whereas the horizontal axis refers to patient groups. The box and bars represent the interquartile range (the 25^th and 75^th percentiles) from the median (the horizontal line) and the 95% confidence interval, respectively. CK-18 fragments levels significantly increased in patients with NASH compared to non-NASH patients (median (Q25, Q75): 372.9 U/L (319.6, 431.4), 248.1 U/L (237.5, 266.6), respectively; P < 0.001).

Figure 2. The model receiver operating characteristic (ROC) curve for the definitive NASH diagnosis in NAFLD patients.