The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity
Open accessAbstract
Background & Aims Full length keratin-18 (FL-K18) and High Mobility Group Box-1 (HMGB1) represent circulating indicators of necrosis during acetaminophen (APAP) hepatotoxicity in vivo. In addition, the caspase-cleaved fragment of K18 (cK18) and hyper-acetylated HMGB1 represent serum indicators of apoptosis and immune cell activation respectively. The study aim was to assess their mechanistic utility to establish the balance between apoptosis, necrosis and immune cell activation throughout the time course of clinical APAP hepatotoxicity. Methods HMGB1 (total, acetylated) and K18 (apoptotic, necrotic) were identified and quantified by novel LC-MS/MS assays in APAP overdose patients (n=78). Results HMGB1 (total; 15.4±1.9ng/ml, p<0.01, acetylated; 5.4±2.6ng/ml, p<0.001), cK18 (5649.8±721.0U/l, p<0.01) and FL-K18 (54770.2±6717.0U/l, p<0.005) were elevated in the sera of APAP overdose patients with liver injury compared to overdose patients without liver injury and healthy volunteers. HMGB1 and FL-K18 correlated with alanine aminotransferase (ALT) activity (R2=0.60 and 0.58 respectively, p<0.0001) and prothrombin time (R2=0.62 and 0.71 respectively, p<0.0001). Increased total and acetylated HMGB1 and FL-K18 were associated with worse prognosis (King’s College Criteria) or patients that died/required liver transplant compared to spontaneous survivors (all p<0.05-0.001), a finding not reflected by ALT and supported by ROC analysis. Acetylated HMGB1 was a better predictor of outcome than the other markers of cell death. Conclusion K18 and HMGB1 represent blood-based tools to investigate the cell death balance clinical APAP hepatotoxicity. Activation of the immune response was seen later in the time course as shown by the distinct profile of acetylated HMGB1 and was associated with worse outcome.
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2 retracted
Yang, H., Lundbäck, P., Ottosson, L., Erlandsson-Harris, H., Venereau, E., Bianchi, M. E., Al-Abed, Y., Andersson, U., Tracey, K. J., & Antoine, D. J. (2012) · Molecular Medicine · doi:10.2119/molmed.2011.00389 · Cited by 407
Self-citationRetractedAntoine, D. J., Williams, D. P., Kipar, A., Laverty, H., & Park, B. K. (2010) · Molecular Medicine · doi:10.2119/molmed.2010.00126 · Cited by 106
Self-citationRetractedRelease of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221
High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal
Lotze, M. T., & Tracey, K. J. (2005) · Nature Reviews Immunology · doi:10.1038/nri1594 · Cited by 2,487
Ostapowicz, G., Fontana, R. J., Schiødt, F. V., Larson, A., Davern, T. J., Han, S. H. B., McCashland, T. M., Shakil, A. O., Hay, J. E., Hynan, L., et al. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-12-200212170-00007 · Cited by 2,227
The current state of serum biomarkers of hepatotoxicity
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Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
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Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome
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Cited by
Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956
EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure
Wendon, J., Cordoba, J., Dhawan, A., Larsen, F. S., Manns, M., Nevens, F., Samuel, D., Simpson, K. J., Yaron, I., & Bernardi, M. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.12.003 · Cited by 917
Self-citationCell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance
Luedde, T., Kaplowitz, N., & Schwabe, R. F. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.07.018 · Cited by 759
Sterile inflammation in the liver
Kubes, P., & Mehal, W. Z. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.09.008 · Cited by 666
Yang, H., Antoine, D. J., Andersson, U., & Tracey, K. J. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.1212662 · Cited by 542
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Metadata
- Authors
- Antoine, D. J., Jenkins, R. E., Dear, J. W., Williams, D. P., McGill, M. R., Sharpe, M. R., Craig, D. G., Simpson, K. J., Jaeschke, H., & Park, B. K.
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 56
- Issue
- 5
- Pages
- 1070-1079
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2117807235
- Cited by
- 309
- References
- 40
- FWCI
- 41.95
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- green
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- Antoine, D. J., Jenkins, R. E., Dear, J. W., Williams, D. P., McGill, M. R., Sharpe, M. R., Craig, D. G., Simpson, K. J., Jaeschke, H., & Park, B. K. (2012). RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2011.12.019
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