| International Session（Workshop）1(JSH・JSGE) |
| Thu. November 5th 9:40 - 12:00 Room 11: Portopia Hotel South Wing Topaz |
| Liver injury mechanism and histological findings at onset of drug-induced liver injury using cytokeratin-18-related cell death markers | |||
| Tomoo Yamazaki1, Satoru Joshita1, Takeji Umemura1 | |||
| 1Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine | |||
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| Background and aims: Drug-induced liver injury (DILI) is a major cause of liver disease. Although serum caspase-cleaved cytokeratin-18 (CK-18) and full-length CK-18 reflecting apoptosis and necrosis, respectively, are prognostic biomarkers of DILI, the mechanism of cell death in DILI remains unknown. This study investigated the relationship of these markers with clinical and histological injury patterns. Methods: Forty-one patients (21 women, median age: 62 years) with DILI who received liver biopsy between 2008 and 2019 were enrolled. Three patients succumbed to DILI. Serum caspase-cleaved (detected as M30) and full-length (detected as M65 and M65ED) CK-18 were examined by ELISA. Results: M30, M65, and M65ED levels correlated significantly with ALT levels (r=0.76, r=0.81, and r=0.78, respectively). In histological activity grade comparisons, all cell death markers were significantly higher in the A≧1 group than in the A0 group (M30: 337 U/L vs. 3038, p<0.05; M65: 384 vs. 2169, p<0.05; and M65ED: 361 vs. 2118, p<0.05). Both M30/M65 and M30/M65ED ratios were significantly higher in the ALT≧85 U/L group than in the ALT<85 group (M30/M65: 0.91 vs. 1.68, p<0.05 and M30/M65ED: 0.85 vs. 1.59, p<0.01). Conclusion: CK-18 reflects histological activity in DILI. Apoptosis appears more frequent with high ALT at DILI diagnosis. |
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Index Term 1: drug-induced liver injury Index Term 2: cytokeratin-18 |
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