Cytokeratin 18 Fragment Level is a Useful Biomarker in Predicting Steatosis and NASH But Not Fibrosis

Background & Aim: Non alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease (from steatosis to cirrhosis). Differentiating various stages is important for therapeutic decision making. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Cytokeratin 18 fragment (CK18-F) levels are a marker of hepatocyte apoptosis. This study was done to evaluate the role of serum CK18-F levels in predicting steatosis, significant NASH and fibrosis when compared to the gold standard i.e. liver biopsy. Methods: 88 patients with biopsy proven NAFLD were enrolled. Histological findings were classified according to the NAFLD activity score (NAS) proposed by the NASH CRN. In addition to basic serum biochemical profile, serum CK18-F level was measured using M30 Apoptosense ELISA. Patients with diabetes mellitus and significant alcohol consumption were excluded. Results: Of the 88 patients, 59 (67%) had a NAS score of ≥5 suggesting histopathological NASH and 33% patients had a score of <5. The mean level of CK18-F was significantly (P 0.024) higher (382 ± 138 U/L) when significant steatosis (steatosis grade 2 or 3 on NAS) was present as compared to no/mild steatosis [(320 ± 106.8 U/L) (steatosis grade 0 or 1)]. CK-18 F level was significantly (P < 0.001) higher (395.82 ± 135.83 U/L) in the group with NASH (NAS ≥ 5) when compared to the group with no NASH (NAS < 5). CK18-F level was insignificantly higher (P 0.087) in the group with fibrosis grade 1–2 (381.9 ± 139.22 U/L) as compared to the group with no fibrosis (334.6 ± 117.05 U/L). The AUROC for detection of NASH for CK18-F was 0.82. A value of 304 U/L was 83.1% sensitive and 82.8% specific for the diagnosis of significant NASH. The AUROC for fibrosis detection using CK18-F was 0.62. Conclusion: Measurement of serum CK18-F was useful in prediction of significant steatosis and NASH but not fibrosis. The authors have none to declare.