Circulating apoptotic and necrotic cell death markers in patients with acute liver injury
Article first published online: 6 APR 2011
© 2011 John Wiley & Sons A/S
Volume 31, Issue 8, pages 1127–1136, September 2011
How to Cite
Craig, D. G. N., Lee, P., Pryde, E. A., Masterton, G. S., Hayes, P. C. and Simpson, K. J. (2011), Circulating apoptotic and necrotic cell death markers in patients with acute liver injury. Liver International, 31: 1127–1136. doi: 10.1111/j.1478-3231.2011.02528.x
- Issue published online: 7 AUG 2011
- Article first published online: 6 APR 2011
- Received 30 October 2010, Accepted 11 March 2011
- acute liver failure;
- liver transplantation;
Background: The host response to cell death underpins the immune activation that follows acute liver injury, and measurement of circulating cell death markers could therefore aid prognostication following paracetamol overdose. Nucleosomes, formed during apoptosis, can complex with high-mobility group box 1 (HMGB1) protein and may play a pathogenic role in liver injury.
Aims: To explore the levels and prognostic significance of nucleosomes, HMGB1, and other cell death markers following acute liver injury.
Methods: Levels of plasma nucleosomes, HMGB1, caspase-cleaved cytokeratin-18 (M30) and total cytokeratin-18 (M65) were measured by immunoassay, in a cohort of 33 patients with paracetamol- and non-paracetamol-induced acute liver injury.
Results: Admission nucleosome levels in paracetamol overdose patients were significantly higher than in chronic liver disease and healthy control subjects, but were similar in paracetamol and non-paracetamol patients (P=0.11). Nucleosome levels were not associated with death or requirement for liver transplantation, fulfillment of poor prognostic criteria or organ failure in paracetamol patients. Nucleosome levels correlated with levels of HMGB1 (r=0.500, P=0.009), alanine aminotransferase (r=0.410, P=0.038) and M65 (r=0.709, P<0.001), but not with M30 (r=0.309, P=0.124). None of the cell death markers analysed improved prognostication in paracetamol patients beyond the King's College criteria.
Conclusions: Plasma nucleosomes are significantly elevated following acute liver injury. Neither apoptotic nor necrotic cell death markers accurately predict survival following paracetamol-induced hepatotoxicity, suggesting that the extent and type of cell death play a limited role in determining outcome.