Cytokeratin 18 Fragment Levels as a Noninvasive Biomarker for Nonalcoholic Steatohepatitis in Bariatric Surgery Patients

Abstract

Nonalcoholic fatty liver disease (NAFLD) is extremely common among morbidly obese patients. We assessed the usefulness of plasma caspase-generated cytokeratin 18 (CK-18) fragments as a novel marker for NAFLD in a bariatric cohort. The cohort consisted of 99 consecutive patients who underwent liver biopsy at the time of bariatric surgery. CK-18 levels were measured by using an enzyme-linked immunosorbent assay before and 6 months after surgery. Patients were subdivided into 4 histologic groups: not NAFLD (normal liver biopsy), nonalcoholic fatty liver (NAFL), borderline diagnosis, and definitive nonalcoholic steatohepatitis (NASH). CK-18 levels were significantly higher in subjects with NASH compared with those with not NAFLD, NAFL, or borderline diagnosis (median [25th quartile, 75th quartile], 389 U/L [275, 839] vs 196 U/L [158, 245], vs 217 U/L [154, 228], or vs 200 U/L [176, 274], respectively; P < .0001). CK-18 levels were significantly higher in subjects with moderate to severe fibrosis versus those with no or mild fibrosis (334.5 U/L [240.5, 896] vs 207 U/L [175, 275], respectively; P = .007). A significant decrease in CK-18 levels was observed in most patients 6 months postoperatively. The area under the receiver operating characteristic curve for NASH diagnosis was estimated to be 0.88 (95% confidence interval, 0.77-0.99). The values with the best combination of sensitivity and specificity were 252 U/L (sensitivity, 82%; specificity, 77%) and 275 U/L (sensitivity, 77%; specificity, 100%). These results support the potential utility of this test for diagnosis and staging of NAFLD before bariatric surgery.