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.
Highlights
We found for the first time that Fibroblast growth factor 21 (FGF21) and Cytokeratin 18 (CK18), both are believed to be potential biomarkers for nonalcoholic fatty liver disease (NAFLD), may play differential roles along the spectrum of NAFLD
FGF21 is more accurate for predicting the onset of simple steatosis, while CK18 including M30 and M65 EpiDeath (M65ED) are better non-invasive biomarkers for predicting the prognosis of NAFLD patients
Fat accumulation in NAFLD is due to increased delivery of free fatty acid (FFA) into the portal vein for conversion to TGs within the liver
Summary
Despite the beneficial effect of FGF21 found in animal studies, circulating FGF21 levels in human are elevated in obesity, metabolic syndrome, type 2 diabetes and coronary artery disease[11]. CK18 is cleaved by caspases and released to the circulation during hepatocyte apoptosis, which is a characteristic feature of liver injury and disease progression in NAFLD13, 14. Recent clinical studies demonstrated that M30 and M65ED are potentially useful to diagnose fatty liver, NASH and fibrosis[13, 15]. No longitudinal epidemiological study focused on the differential roles of FGF21 and CK18 in NAFLD spectrum In this prospective study, we aimed at assessing FGF21, CK18 M30 and M65ED levels during different stages in the spectrum of NAFLD and evaluating their respective role in early identification and predicting the prognosis of NAFLD patients to investigate their clinical significance
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