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CK-18 levels inadequate as stand-alone NASH, fibrosis test

Levels of cytokeratin-18 did not perform well as a stand-alone method to distinguish nonalcoholic fatty liver disease and nonalcoholic steatohepatitis or determine fibrosis severity in a recent study.

Researchers evaluated levels of plasma caspase-generated cytokeratin-18 fragments (CK-18), adipose tissue, insulin resistance and hepatic fat in 424 middle-aged overweight or obese patients with no evidence of serious chronic illness. The cohort included 300 patients with nonalcoholic fatty liver disease (NAFLD), diagnosed via magnetic resonance imaging and spectroscopy (MRS) in 229 cases, liver biopsy in 66 cases and positive ultrasound in five patients. Nonalcoholic steatohepatitis (NASH) was observed in 199 cases out of 318 liver biopsy recipients.

Among 275 patients who underwent MRS, median levels of CK-18 were greater in those with NAFLD (209 U/L vs. 122 U/L among those without) or NASH (232 U/L vs. 170 U/L) (P<.001 for both).

Investigators noted that plasma CK-18 levels rose with severity of steatosis, inflammation and fibrosis. Significant overlap occurred across disease severity, with concentration differences observed between patients with steatosis grade 0 compared with grades 2 (P=.01) and 3 (P<.01), with inflammation grade 0 compared with grade 2 (P=.02), and with fibrosis stage 0 compared with stages 1 and 3 (P<.001 for both), but not stage 2 (P=.14).

AUROC analysis of CK-18 yielded values of 0.77 (0.71-0.84) for the prediction of NAFLD, 0.65 (0.59-0.71) for NASH and 0.68 (0.61-0.75) for fibrosis. Sensitivity was 63%, 58% and 54% and specificity was 83%, 68% and 85%, respectively.

“The current study suggests that the value of CK-18 as a stand-alone test to distinguish NAFLD from NASH or to determine the severity of NASH fibrosis may be more limited than previously thought,” the researchers concluded. “However, combining this variable with other biologically plausible markers may ultimately prove to be more accurate at diagnosing NASH and determining fibrosis severity.”

Disclosure: Researcher Ariel E. Feldstein is listed as a co-inventor on pending and issued patents filed by Cleveland Clinic and the University of California, San Diego that refer to the use of biomarkers in fatty liver disorders.