Data for 196 subjects were analysed.MACK-3 was good for diagnosis of fibrotic NASH (area under receiver-operating characteristics curve [AUROC] 0.80), comparable to the Fibrosis-4 index (FIB4) and the NAFLD fibrosis score (NFS) and superior to the BARD score and CK18.
Despite metabolic similarities most models (except those with chemically or genetically induced porphyria or keratin 18-deficiency) fail to develop the morphologic key features of NASH, namely hepatocyte ballooning and formation of histologically and immunohistochemically well-defined Mallory-Denk-Bodies (MDBs).
Multivariate analysis showed that cytokeratin-18 fragment (CK18-F) levels (≥278 U/L) (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.42-14.00; p = 0.010) and the FIB-4 index (≥1.46) (OR, 4.54; 95% CI, 1.93-29.50; p = 0.004) were independently associated with prediction of NASH.
Multiple logistic regression analysis identified hyaluronic acid (HA) (OR 1.014; 95% CI 1.002-1.026; p = 0.024), FIB-4 index (OR 2.097; 95% CI 1.177-3.735; p = 0.012), and cytokeratin-18 fragments (CK-18F) (OR 1.002; 95% CI 1.001-1.002; p < 0.001) as factors independently associated with the diagnosis of NASH.
It showed good predictability for NASH in the NAFLD group [area under the receiver operating characteristic curves (AUROC) = 0.831] and was validated in the CHB group (AUROC = 0.833); this characteristic was superior to that of cytokeratin-18 and alanine transaminase.
The diagnostic value of miR-34a for NASH (area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but miR-16 showed a limited performance in the diagnosis of significant fibrosis in NASH.
Herein, we aimed to study the association between hepatic fat accumulation as assessed by magnetic resonance imaging and circulating levels of cytokeratin-18 (CK-18) fragments, a robust NASH biomarker, and to explore the impact on this association of ethnicity, insulin resistance, and single nucleotide polymorphisms (SNPs) associated with steatosis (rs738409 in the PNPLA3, rs1260326 in the GCKR) or NASH severity (rs2645424 in the FDFT1).
Currently, the diagnosis of NASH requires a liver biopsy, however, serum based markers of hepatocyte apoptosis such as cytokeratin-18 fragments offer promise as accurate non-invasive diagnostic tests.
Cytokeratin-18 fragments increased significantly postprandially in both groups but more consistently in patients with NASH; their increase was predicted by postprandial adiponectin and FFA responses.