Complementary Role of Fibroblast Growth Factor 21 and Cytokeratin 18 in Monitoring the Different Stages of Nonalcoholic Fatty Liver Disease

Guangyu Wu, Huating Li, Qichen Fang, Jing Zhang, Mingliang Zhang, Lei Zhang, Liang Wu, Xuhong Hou, Junxi Lu, Yuqian Bao, Weiping Jia, Guangyu Wu, Huating Li, Qichen Fang, Jing Zhang, Mingliang Zhang, Lei Zhang, Liang Wu, Xuhong Hou, Junxi Lu, Yuqian Bao, Weiping Jia

Abstract

Fibroblast growth factor 21 (FGF21) and cytokeratin 18 (CK18) were previously reported to be elevated in nonalcoholic fatty liver disease (NAFLD). We aim to analyze the differential roles of FGF21, cell apoptosis marker CK18 fragment M30 and total cell death marker CK18 M65ED in monitoring the different stages of NAFLD spectrum in a population-based prospective cohort comprising 808 Chinese subjects. Predictive performances for monitoring the different stages of NAFLD were assessed by logistic regression and receiver-operating characteristic (ROC) curves. We found baseline FGF21 but not CK18 level was an independent predictor for the development of simple steatosis. NAFLD patients who had remission during follow-up had significantly lower baseline M30 levels than those who sustained NAFLD (84.74U/L [53.26-135.79] vs. 118.47U/L [87.16-188.89], P = 0.012). M65ED was independently predictive of progressing to suspected non-alcoholic steatohepatitis (NASH) in NAFLD patients. These results suggest that FGF21 can be used for early identification of hepatic steatosis. On the other hand, CK18 including M30 and M65ED, are predictive of the prognosis of NAFLD patients. FGF21 and CK18 might play differential roles and have complementary value in non-invasive identification and monitoring the outcome of NAFLD patients.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Comparison of FGF21, M30 and M65ED levels at baseline in different groups. (a) Baseline FGF21, M30, M65ED levels in subjects who developed simple steatosis (n = 70) and who did not (n = 363). (b) Baseline FGF21, M30, M65ED levels in subjects who sustained NAFLD (n = 93) and who had remission during follow-up (n = 30). (c) Baseline FGF21, M30 and M65ED levels in subjects who sustained simple steatosis (n = 69) and subjects who developed suspected NASH (n = 24). Data represent median (interquartile range). *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 2
Figure 2
ROC curves for predicting the development and progression of NAFLD. (a) ROC curves of FGF21, M30 and M65ED for predicting the onset of simple steatosis. (b) ROC curves for predicting the remission of NAFLD during follow-up. (c) ROC curves for predicting suspected NASH in subjects who sustained NAFLD.
Figure 3
Figure 3
Relationship between baseline FGF21, CK18 M30 and CK18 M65ED with liver stiffness after 8-year follow-up. (a) Correlation of baseline FGF21 levels and liver stiffness evaluated by FibroScan after 8-year follow-up. (b) Correlation of baseline CK18 M30 levels and liver stiffness. (c) Correlation of baseline CK18 M65ED levels and liver stiffness.

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