Cytokeratin 18 fragment is associated with steatosis-associated fibrosis estimator score and lipid in patients with steatotic liver disease

Figure 1 Relationship between cytokeratin 18 fragment and clinical factors. A: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), ferritin, triglycerides (TG), high-density lipoprotein (HDL), and hemoglobin A1c (HbA1c), which were noted to correlate with cytokeratin 18 fragment (CK18F), were used in a multiple regression analysis. AST, ALT, and triglyceride (TG) were associated with CK18F; B: In the combined Figure 1A, TG and HDL were changed to TG/HDL and the same analysis was performed. AST, ALT, and TG/HDL were associated with CK18F; C: Multiple logistic regression analysis for CK18F > 260 U/L (high CK18F). In non-invasive tests, steatosis-associated fibrosis estimator (SAFE) score and FibroScan-aspartate aminotransferase (FAST) were associated with CK18F. SAFE score was divided as follows: (1) High (> 100); (2) Moderate (0-100); and (3) Low (< 0). FAST was divided as follows: (1) High (> 0.35); and (2) Low (< 0.35). Low-risk, moderate-risk, and high-risk (LMH) SAFE and low-risk and high-risk (LMH) FAST corresponded with CK18F.

Figure 2 Relationship between severity classification according to non-invasive test and cytokeratin 18 fragment values. A: Classification according to steatosis-associated fibrosis estimator score. P value for analysis of variance is indicted in the figure. Cytokeratin 18 fragment (CK18F) was higher in the high group than those in the low and moderate groups (Dunn test); B: Classification according to FibroScan-aspartate aminotransferase score. P value for the Mann–Whitney U test is indicated in the figure; C: Classification according to liver stiffness (LS). High LS group is > 8 Kpa; D: High LS group is > 10 Kpa. Y axis is CK18F (U/L). ANOVA: Analysis of variance; SAFE: Steatosis associated fibrosis estimator; FAST: FibroScan-aspartate aminotransferase.

Figure 3 Triglycerides and high-density lipoprotein influenced cytokeratin 18 fragment levels. A: High triglycerides (TGs) were > 126 mg/dL. Figures in brackets were the number of patients. P value for the Mann–Whitney U test is indicated in the figure. Y axis is cytokeratin 18 fragment (CK18F) (U/L); B: High CK18F rate in the normal and high TG groups. P value for the χ² test is shown in the figure; C: Low high-density lipoprotein (HDL) group with values < 56 mg/dL; D: High CK18F rate in the normal and low HDL groups; E: High TG and low HDL scores were calculated with high TG as 1 point and low HDL as 1 point. P value for the analysis of variance test is shown on the figure. P values between groups for the Dunn test; F: High CK18F rate for high TG and low HDL score. ANOVA: Analysis of variance; TGHHDLL: Triglycerides high (> 126 mg/dL) and high-density lipoprotein low (≤ 56 mg/dL).

Figure 4 Criteria for high triglycerides (≥ 126 mg/dL) and low high-density lipoprotein (≤ 56 mg/dL) have more effect on high cytokeratin 18 fragment than the settings for high/treatment triglycerides (≥ 150 mg/dL or lipid-lowering treatment) and low/treatment high-density lipoprotein (≤ 39 mg/dL for men and 50 mg/dL for women or lipid-lowering treatment). A: Effect of high triglycerides (TGs) (≥ 126 mg/dL), low high-density lipoprotein (HDL) (≤ 56 mg/dL), high/treatment TG (≥ 150 mg/dL or lipid-lowering treatment), and low/treatment HDL (39 mg/dL in men and ≤ 50 mg/dL in women or lipid-lowering treatment) on high cytokeratin 18 fragment (CK18F) was investigated using multivariate logistic regression analysis; B: Effect of high TG (≥ 126 mg/dL), low HDL (≤ 56 mg/dL), and high TG and low HDL on high CK18F was evaluated using multivariate logistic regression analysis; C: The criteria for high TG and low HDL in cardiometabolic risk factor (CMRF) were replaced by TG ≥ 126 mg/dL and HDL < 56 mg/dL in modified CMRF (mCMRF), and the effect of CMRF and mCMRF on high CK18F was evaluated using multivariate logistic regression analysis. OR: Odds ratio; TGHHDLL: Triglycerides high (> 126 mg/dL) and high-density lipoprotein low (≤ 56 mg/dL).