Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study. Issue 3 (5th February 2023)

• Record Type: Journal Article
• Authors: Zhang, Huai; Rios, Rafael S.; Boursier, Jerome; Anty, Rodolphe; Chan, Wah-Kheong; George, Jacob; Yilmaz, Yusuf; Wong, Vincent Wai-Sun; Fan, Jiangao; Dufour, Jean-François; Papatheodoridis, George; Chen, Li; Schattenberg, Jörn M.; Shi, Junping; Xu, Liang; Wong, Grace Lai-Hung; Lange, Naomi F.; Papatheodoridi, Margarita; Mi, Yuqiang; Zhou, Yujie; Byrne, Christopher D.; Targher, Giovanni; Feng, Gong; Zheng, Minghua
• Editors: Ji, Yuanyuan
• Is Part Of: Chinese medical journal. Volume 136:Issue 3(2023)
• Page Start: 341
• Page End: 350
• Publication Date: 2023-02-05
• Subjects: Apoptosis -- Diagnosis -- Cytokeratin-18 -- Liver histology -- Non-alcoholic steatohepatitis -- Non-alcoholic fatty liver disease; Medicine -- Periodicals; Medicine, Oriental -- Periodicals; Medicine; Medicine, Oriental; Medicine; Medicine, East Asian Traditional; Periodicals; Electronic journals; 610.5
• DOI: 10.1097/CM9.0000000000002603
• Languages: English
• ISSNs: 0366-6999

Abstract

Abstract: Background: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. Methods: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). Results: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69–1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P < 0.001, P = 0.026 and P = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714–0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%–59%]) and positive predictive value (59%) were not ideal. Conclusion: This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.