Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study.

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, Jun-Ping; Xu, Liang; Wong, Grace Lai-Hung; Lange, Naomi F; Papatheodoridi, Margarita; Mi, Yuqiang; Zhou, Yujie; ... (2023). Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study. Chinese medical journal, 136(3), pp. 341-350. Wolters Kluwer 10.1097/CM9.0000000000002603

Preview

Text Hepatocyte_apoptosis_fragment_product.402.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (492kB) | Preview

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 including 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.

CONCLUSIONS

This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.

Interest & Impact

Downloads

86 since deposited on 28 Feb 2023
60 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item