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

Zhang H., Rios R. S., Boursier J., Anty R., Chan W., George J., ...More

Chinese medical journal, vol.136, pp.341-350, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 136
  • Publication Date: 2023
  • Doi Number: 10.1097/cm9.0000000000002603
  • Journal Name: Chinese medical journal
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.341-350
  • Keywords: Apoptosis, Diagnosis, Cytokeratin-18, Liver histology, Non-alcoholic steatohepatitis, Non-alcoholic fatty liver disease, FATTY LIVER-DISEASE, NONINVASIVE ASSESSMENT, PLASMA CYTOKERATIN-18, BIOMARKER, TRANSPLANTATION, METAANALYSIS, ASSOCIATION, FIBROSIS, OBESE
  • Recep Tayyip Erdoğan University Affiliated: No


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.