Cytokeratin 18, Alanine Aminotransferase, Platelets and Triglycerides Predict the Presence of Nonalcoholic Steatohepatitis

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the critical public health problems in China. The full spectrum of the disease ranges from simple steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma(HCC). The infiltration of inflammatory cells characterizes NASH. This characteristic contributes to the progression of hepatitis, fibrosis, cirrhosis, and HCC. Therefore, distinguishing NASH from NAFLD is crucial.Objective and MethodsNinety-five patients with NAFLD, 44 with NASH, and 51 with non-NASH were included in the study to develop a new scoring system for differentiating NASH from NAFLD. Data on clinical and biological characteristics, as well as blood information, were obtained. Cytokeratin-18 (CK-18) fragments levels were measured using an enzyme-linked immunosorbant assay.ResultsSeveral indexes show significant differences between the two groups, which include body mass index (BMI), waist-on-hip ratio (WHR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), platelets, uric acid (UA), hs-C-reactive protein (hs-CRP), triglycerides (TG), albumin (ALB), and CK-18 fragments (all P < 0.05). The CK-18 fragment levels showed a significant positive correlation with steatosis severity, ballooning, lobular inflammation, and fibrosis stage (all P < 0.05). Therefore, a new model that combines ALT, platelets, CK-18 fragments, and TG was established by logistic regression among NAFLD patients. The AUROC curve in predicting NASH was 0.920 (95% CI: 0.866 - 0.974, cutoff value = 0.361, sensitivity = 89%, specificity = 86%, positive predictive value = 89%, negative predictive value = 89%). ConclusionThe novel scoring system may be considered as a useful model in predicting the presence of NASH in NAFLD patients.

Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance

“…201 Despite clinical trials of multiple molecular targets in patients with NASH, 202 no effective pharmacological strategy against NASH-induced liver fibrosis and HCC has yet been established in clinical practice, highlighting the need to identify signaling pathways regulating the transition from NAFLD to NASH. This transition is typically accompanied by elevated ALT levels, 173 and 203 indicating the pivotal role of cell death in this process. Of all cell death pathways, apoptosis is the best characterized form in this context.…”

Usefulness of Cytokeratin-18M65 in Diagnosing Non-Alcoholic Steatohepatitis in Japanese Population

“…Recently, serum CK-18M65 released in NAFLD patients in the process of the cellular death has been proposed as a possible serum biomarker of NASH [27,28]. The increased serum levels of CK-18 fragments, in some clinical cohorts of obese patients or those with insulin resistance, are associated with hepatocyte injury, inflammation and fibrosis [29. ]…”

“…The ROC curve and the area under ROC curve were used to assess the utility of parameters in the diagnosis of NASH [29]. Moreover, in comparing between NASH and SS, the level of CK-18M65 detected by M65 ELISA, around 548 U/l, correctly predicted NASH with a sensitivity of 60.00%, a specificity of 85.7% and an AUC value of 0.7369 (fig.…”

Impact of Co-Morbidities in Non Alcoholic Fatty Liver Disease among Type 2 Diabetes Mellitus

“…The increased FFA level boosts TG and VLDL release as well as triggers oxidative stress and lipid peroxidation, all of which are related with the development of NAFLD. [19,20] …”