Identification and multicentric validation of soluble CDCP1 as a robust serological biomarker for risk stratification of NASH in obese Chinese

The definitive diagnosis of non-alcoholic steatohepatitis (NASH) currently relies on invasive and labour intensive liver biopsy. Here, we identified soluble CUB Domain Containing Protein 1 (sCDCP1) as a top ranked non-invasive biomarker for NASH using Olink-based proteomics in obese individuals with liver biopsies. Both the circulating concentration and hepatic mRNA abundance of sCDCP1 were significantly elevated in NASH patients and correlated closely with each histological feature of NASH. In the pooled multicenter validation cohort, sCDCP1 as a standalone biomarker achieved an AUROC of 0.838 (95% CI 0.789-0.887) for diagnosing NASH, better than cytokeratin-18 and other noninvasive tests. Furthermore, C-DAG model established by the combination of sCDCP1 with diabetes, AST and gender accurately rule-in and rule-out both NASH and fibrotic NASH (grey zones < 20%). Thus, sCDCP1-based non-invasive tests can be potentially implemented for screening and early diagnosis of NASH and for ruling-out those low-risk individuals to avoid unnecessary liver biopsies.