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Combination of serum biomarkers can accurately diagnose NAFLD, NASH
Combining cytokeratin-18 fragment and fibroblast growth factor 21 can improve the accuracy of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis diagnosis, according to recent study results.
The study included 146 patients with nonalcoholic fatty liver disease (NAFLD) and 74 matched controls. Researchers measured participants’ serum levels of cytokeratin-18 fragment (CK-18), adipocyte fatty acid binding protein (AFABP) and fibroblast growth factor 21 (FGF21) to determine their usefulness as biomarkers for NAFLD and nonalcoholic steatohepatitis (NASH). Patients with NAFLD were further stratified according to the presence of NASH (64 patients with non-NASH and 82 with NASH).
Median serum levels for the three groups were as follows:
- Controls: 103 U/L CK-18, 15.4 ng/mL AFABP and 104 pg/mL FGF21
- Non-NASH NAFLD: 263 U/L CK-18, 18.9 ng/mL AFABP and 249 pg/mL FGF21
- NASH NAFLD: 418 U/L CK-18, 19.4 ng/mL AFABP and 354 pg/mL FGF21
The difference in levels between controls and patients with NAFLD was significant for all biomarkers (P<.001 for each). Differences in levels between patients with non-NASH NAFLD and NASH NAFLD were significant for CK-18 (P<.001) and FGF21 (P=.016) but not AFABP (P=.06).
AUROC analysis indicated that CK-18 was the most accurate predictor for NAFLD (0.91, 95% CI, 0.87-0.95 compared with 0.66, 95% CI, 0.59-0.74 for AFABP, and 0.84, 95% CI, 0.79-0.90 for FGF21), and also better able to discern NASH NAFLD from non-NASH NAFLD (AUROC=0.70, 95% CI, 0.61-0.78 compared with 0.59, 95% CI, 0.50-0.68 for AFABP and 0.62, 95% CI, 0.53-0.71 for FGF21). Investigators found that CK-18 combined with FGF21 improved accuracy when excluding and diagnosing NASH compared with CK-18 on its own (71% negative and 77% positive predictive value for CK-18 alone compared with 74% negative and 82% positive in combination).
“In this prospective cohort study, CK-18 and FGF21 had high accuracy in diagnosing NAFLD,” the researchers wrote. “Among NAFLD patients, these biomarkers also had moderate accuracy in detecting NASH, and the accuracy could be improved by combining the two biomarkers. … based on this cohort, we demonstrated that the biomarkers not only predicted NASH … but also reflected the changes in histology with time.”