부산대학교 도서관

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. [Copyright &y& Elsevier]