AUTHOR=Wang Qingling , Zhou Da , Wang Mingjie , Zhu Mingyu , Chen Peizhan , Li Hu , Lu Meng , Zhang Xinxin , Shen Xizhong , Liu Taotao , Chen Li TITLE=A Novel Non-Invasive Approach Based on Serum Ceruloplasmin for Identifying Non-Alcoholic Steatohepatitis Patients in the Non-Diabetic Population JOURNAL=Frontiers in Medicine VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.900794 DOI=10.3389/fmed.2022.900794 ISSN=2296-858X ABSTRACT=Background and aim: Few noninvasive models were established to identify nonalcoholic steatohepatitis (NASH) patients, and liver biopsy remains the gold standard in the clinic. Decreased serum ceruloplasmin (CP) is reported in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a noninvasive model incorporating CP for identifying NASH from NAFLD without Type 2 diabetes mellitus (T2DM). Methods: A total of 138 biopsy-proven NAFLD patients without T2DM were enrolled. The CP ratio was calculated for standardization as the CP value divided by the lower limit of normal. The clinical, anthropometric, biochemical, and histological parameters were compared between the low and high CP ratio groups divided by the median value. Multivariate logistic regression analysis was performed to develop a model for identifying NASH from NAFLD patients. Results: The medians of the high (n=69) and low (n=69) CP ratio groups were 1.43 (1.28-1.61) and 1.03 (0.94-1.12), respectively. A comparison of the two groups showed that the severity of steatosis, hepatocellular ballooning, inflammation activity, fibrosis, and liver iron deposition decreased along with the CP ratio (p<0.05). The median CP ratio of patients with NASH was significantly lower than those with NAFL [1.15 (1.01-1.41) vs. 1.33 (1.24-1.54), p=0.001]. A novel model which consists of the CP ratio, BMI, and aspartate aminotransferase (AST) was developed. The AUCs of the model in discriminating NASH from NAFLD were 0.796 (0.694-0.899) and 0.849 (0.713-0.984) in the training and validation groups, and 0.820 (0.626-1.000), 0.831(0.685-0.976), and 0.801 (0.567-1.000) in patients with normal serum alanine aminotransferase, AST, and both levels, respectively. Conclusions: Decreased CP ratio is associated with more severe histological activity, a diagnosis of NASH, and hepatic iron deposition among NAFLD patients without T2DM. The CP ratio model could be served as a noninvasive approach to identify NASH patients, which might reduce the need for liver biopsy.