期刊
JOURNAL OF HEPATOLOGY
卷 60, 期 1, 页码 167-174出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2013.07.042
关键词
Cytokeratin-18; Fatty liver; NAFLD; NASH; Insulin resistance; Diabetes
资金
- Burroughs Wellcome Fund
- American Diabetes Association [1-08-CR-08]
- VA Merit Award [1 I01 CX000167-01]
- NIH [DK076852, DK082451]
- Veterans Affairs Medical Research Fund
- National Center for Research Resources [UL 1RR025767]
Background & Aims: Liver biopsy is the only reliable way of diagnosing and staging NASH but its invasive nature limits its use. Plasma caspase-generated cytokeratin-18 fragments (CK-18) have been proposed as a non-invasive alternative. We studied its clinical value in a large multiethnic NAFLD population and examined its relationship to clinical/metabolic/histological parameters. Methods: 424 middle-aged subjects in whom we measured adipose tissue, liver and muscle insulin resistance (IR), liver fat by MRS (n = 275) and histology (n = 318). Results: Median CK-18 were elevated in patients with vs. without NAFLD by MRS (209 [IQR: 137-329] vs. 122 [IQR: 98-155] U/L) or with vs. without NASH (232 [IQR: 151-387] vs. 170 [IQR: 135-234] U/L, both p < 0.001). Plasma CK-18 raised significantly with any increase in steatosis, inflammation and fibrosis, but there was a significant overlap across disease severity. The CK-18 AUROC to predict NAFLD, NASH or fibrosis were 0.77 (95% CI = 0.71-0.84), 0.65 (95% CI = 0.59-0.71) and 0.68 (95% CI = 0.61-0.75), respectively. The overall sensitivity/specificity for NAFLD, NASH and fibrosis were 63% (57-70%)/83% (69-92%), 58% (51-65%)/68% (59-76%) and 54% (44-63%)/85% (75-92%), respectively. CK-18 correlated most strongly with ALT (r = 0.57, p < 0.0001) and adipose tissue IR (insulin-suppression of FFA: r = -0.43; p < 0.001), less with steatosis, lobular inflammation and fibrosis (r = 0.28-0.34, all p < 0.001), but not with ballooning, BMI, metabolic syndrome or T2DM. Conclusions: Plasma CK-18 has a high specificity for NAFLD and fibrosis, but its limited sensitivity makes it inadequate as a screening test for staging NASH. Whether combined as a diagnostic panel with other biomarkers or clinical/laboratory tests may prove useful requires further study. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
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