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- Title
Plasma biomarkers to study mechanisms of liver injury in patients with hypoxic hepatitis.
- Authors
Weemhoff, James L.; Woolbright, Benjamin L.; Jenkins, Rosalind E.; McGill, Mitchell R.; Sharpe, Matthew R.; Olson, Jody C.; Antoine, Daniel J.; Curry, Steven C.; Jaeschke, Hartmut
- Abstract
Background & Aims Hypoxic hepatitis is a clinical condition precipitated by prolonged periods of oxygen deprivation to the liver. It can have several underlying causes. Despite its prevalence in critically ill patients, which can reach upwards of 10%, very little is known about the mechanisms of injury. Thus, we set out to measure previously identified circulating biomarkers in an attempt to describe mechanisms of injury following hypoxic hepatitis. Methods Plasma from patients diagnosed with hypoxic hepatitis was collected for this study. Biomarkers of hepatocellular injury, mitochondrial damage and cell death were measured. These results were compared against results obtained from well-characterized acetaminophen overdose patients. Results At peak injury, ALT measured 4082±606 U/L and gradually decreased over 5 days, corresponding to the clinically observed pattern of hypoxic hepatitis. Levels of GDH showed a similar pattern, but neither ALT nor GDH were significantly higher in these patients than in acetaminophen patients. Plasma levels of DNA fragments mimicked hepatocellular injury as measured by ALT and mi RNA-122. Interestingly, we found a significant increase in caspase-cleaved cytokeratin-18; however, the full-length form greatly exceeded the cleaved form at the time of maximum injury (45837±12085 vs 2528±1074 U/L). We also found an increase in ac HMGB1 at later time points indicating a possible role of inflammation, but cytokine levels at these times were actually decreased relative to early time points. Conclusions The mechanism of injury following hypoxic hepatitis involves mitochondrial damage and DNA fragmentation. Importantly, necrosis, rather than apoptosis, is the main mode of cell death.
- Subjects
HEPATITIS; LIVER diseases; MEDICAL care; PLASMA gases; ACETAMINOPHEN; DISEASE risk factors
- Publication
Liver International, 2017, Vol 37, Issue 3, p377
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.13202