Serum cytokeratin-18 and its relation to liver fibrosis and steatosis diagnosed by FibroScan and controlled attenuation parameter in nonalcoholic fatty liver disease and hepatitis C virus patients

Abstract

Background Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of chronic liver disease worldwide. Multiple diagnostic noninvasive methods for NAFLD were studied (both serological and imaging), either single or combined. Attention has been focused on cytokeratin-18 (CK18) as a novel serological marker for the diagnosis of steatosis/fibrosis in NAFLD and hepatitis C virus (HCV) patients. Aim The aim of this study was to evaluate serum CK18 in NAFLD and HCV fibrosis/steatosis and also to correlate its performance with the diagnostic accuracy of transient elastography (TE) and controlled attenuation parameter (CAP) in the diagnosis of fibrosis/steatosis in these patients. Patients and methods Three equal groups of participants were enrolled (n=135): group I included patients with chronic HCV, group II included NAFLD patients, and group III included control participants. For all groups, TE/CAP and labs including serum CK18 were performed. Liver biopsy was performed for the NAFLD group. Results Serum CK18 was significantly higher in the NAFLD group (19.01±3.49 ng/ml) versus the HCV group (8.95±1.06 ng/ml) and the control group (4.83±1.6 ng/ml) (P<0.001). The CK18 levels in biopsy stages (steatosis, ballooning, inflammation, and fibrosis) and FibroScan/CAP degrees showed that CK18 increased significantly with steatosis and fibrosis stages (biopsy or FibroScan/CAP), but did not reach significance with ballooning or inflammation grades. CK18 was significantly different in nonalcoholic steatohepatitis versus non-nonalcoholic steatohepatitis patients (P=0.041). The best CK18 cutoff to detect steatosis (S≥2) in NAFLD and HCV was 11.65 and 6.84 ng/ml, respectively with an overall sensitivity and specificity over 97%. The CK18 cutoff for significant fibrosis (F≥2) by FibroScan in the NAFLD/HCV groups was 9.115 ng/ml, with 62.5%/69.2% sensitivity/specificity (P=0.031). However, inflammation had a cutoff with a marginal P value (P=0.080), and a reliable cutoff for ballooning was not attained (P=0.386). There was a positive correlation between CK18 and fibrosis (by FibroScan) in the NAFLD and HCV groups (P<0.05). The correlation between CK18 and steatosis in CAP and the nonalcoholic fatty liver disease activity score was very good (P<0.001). Conclusion Serum CK18 is related strongly to the development/progression of NAFLD and HCV-related fibrosis/steatosis. TE was correlated highly with liver biopsy results. The combination of CK18 with other noninvasive modalities increases the diagnostic yield of these tests.

Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans

“…55 Other studies suggest an added value of CK-18, a component of the cytoskeleton of hepatocytes which is released in the blood upon cell damage 56 in nonalcoholic steatohepatitis and viral disease. [57][58][59] Our study extends current data on CK-18 also to ALD. The good diagnostic power of our integrated approach might prove useful for monitoring liver disease progression and/or regression in AUD patients.…”

Accuracy of cytokeratin 18 (M30 and M65) in detecting non-alcoholic steatohepatitis and fibrosis: A systematic review and meta-analysis

“…Seven studies were scored as unclear risk of bias in the reference standard domain, for failing to report whether biopsy reviewers were blinded to clinical data [8,9,29,32,40,49,57]. Only three studies were classified as at high risk of bias for flow and timing [10,25,40]. We further graded four studies with high concern regarding applicability in the patient selection domain [30,46,54,57].…”

Changes in plasma circulating microvesicles in patients with HCV‐related cirrhosis after treatment with direct‐acting antivirals

“…Specific keratins are expressed in different epithelia and hepatocytes express only one pair of keratins (K8 and K18). Serum levels of cytokeratin‐18 have been shown to correlate with FibroScan ® values, severity of cirrhosis and HCV‐related fibrosis progression . In addition, serum levels of cytokeratin‐18 were used to indirectly measure hepatocyte MV levels, and as previously mentioned, correlated with the severity of cirrhosis .…”