In addition to fibrosis, steatosis is increasingly recognized as a cofactor influencing the progression of liver injury. We have recently selleck kinase inhibitor shown that serum levels of caspase-cleaved CK-18 correlate with the severity of liver steatosis in chronic HCV infection,19 a finding that was subsequently confirmed in pediatric HCV patients.39 In this study, we evaluated whether detection of caspase-cleaved or total CK-18 can discriminate between minimal (≤10%) and higher grades of steatosis (>10%) in 121 patients with chronic liver diseases including 52 HCV patients and 22 NAFLD patients. We found significantly higher levels of both biomarkers in patients with liver steatosis compared with healthy controls. Our
results further revealed a better diagnostic performance of the M65 assays with improved AUC values to detect relevant steatosis
compared with the M30 assay. In contrast to the M30 marker, detection of total CK-18 by both M65 ELISAs discriminated between minimal or relevant steatosis. Because the two patient cohorts showed no significant differences in fibrosis, total CK-18 levels reflect steatosis independently of liver fibrosis. NAFLD is one of the most common causes of chronic liver disease, ranging from simple steatosis to NASH and cirrhosis. A variety of panel markers using the combination of different variables for NASH diagnosis has been proposed.6 Single markers such as aminotransferases are not suitable to distinguish between NAFL and NASH. In two studies, NASH was diagnosed in up to 59% of NAFLD patients NVP-LDE225 cell line despite normal ALT levels.40, 41 Intriguingly, Wieckowska et al.24 showed that plasma levels of CK-18 fragments might allow the discrimination between NASH and NAFL patients. Subsequent studies Clomifene confirmed an increase of caspase-cleaved CK18 fragments in NASH patients, supporting the assertion that CK-18 may be useful
for the diagnosis of NASH.25, 26, 42-45 In view of these findings we evaluated whether the M30 and M65 assays could distinguish NASH patients from those with simple steatosis. Both assays could discriminate between NASH and NAFL and between NASH and healthy individuals. Surprisingly, unlike the M30 assay, only serum levels of total CK-18 significantly discriminated between NAFL patients and healthy controls. This differentiation is important because it was demonstrated that 58% of NAFL patients progress toward NASH and 28% among them show fibrosis progression within 3 years.46 Measurement of total CK-18 levels also revealed higher significance for distinguishing between NAFL and NASH compared with the M30 assay. In addition, compared with the M30 marker, both M65 assays revealed a better accuracy with improved AUC values to detect NASH. The fibrosis stages of NAFL and NASH patients were similar in our cohort and did therefore not influence the power of the biomarkers to discriminate between both groups.