Differential evaluation of hepatocyte apoptosis and necrosis in acute liver injury
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Published on: November 27, 2019
Mio Onodera1, Yasuhiro Takikawa, Keisuke Kakisaka
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, 020-8505, Japan.
Aim:
The significance of cytokelatin-18 fragment cleaved by caspase-3 (CK-18-fr) and high mobility group box-1 (HMGB-1) were evaluated experimentally and clinically for the differential evaluation of hepatocyte apoptosis and necrosis in patients with acute hepatic injury (AHI).
Methods:
In this study, typical apoptosis and necrosis were induced in HepG2 cells by staurosporin (STS) and hydrogen peroxide, respectively. Intracellular generation of CK-18-fr and extracellular leakage of CK-18-fr and HMGB-1 were determined. In the clinical study, serum CK-18-fr and HMGB-1 levels in 84 patients with AHI of varied severity and etiology were measured and compared with conventional liver tests.
Results:
In the experimental study, CK-18-fr was rapidly increased after STS stimulation, and peaked after 6 h inside the cells but increased in the medium 12 h after stimulation, while hydrogen peroxide stimulation caused no increase either in- or outside the cells. Extracellular HMGB-1 levels markedly increased after hydrogen peroxide stimulation, but did not change after STS stimulation. In the clinical study, serum CK-18-fr increased in correlation with serum aminotransferase, but not other liver tests or markers of disease severity of AHI,. Serum HMGB-1 levels mildly increased without any correlation to liver test or disease severity. Serum HMGB-1 levels in patients with circulation disturbance was significantly higher than that in patients with other etiologies.
Conclusion:
The simultaneous determination of the serum CK-18-fr and HMGB-1 may be useful in the differential diagnosis of hetocellular death in AHI, which is primarily due to apoptosis except in patients with circulation disturbance.
