Serum Apoptosis Markers in Acute Liver Failure: A Pilot Study

Anna E. Rutherford, Linda S. Hynan, Carolina B S Borges, David G. Forcione, Jason T. Blackard, Wenyu Lin, April R. Gorman, Obaid Shakil Shaikh, Adrian Reuben, Edwyn Harrison, K. Rajender Reddy, William M. Le, Raymond T. Chung

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Background & Aims: We sought to determine whether circulating apoptotic markers are altered in acute liver failure (ALF), differ with etiology, or predict clinical outcome in this condition. Methods: Serum levels of soluble Fas (sFas), tumor necrosis factor-alpha (TNF-α), hepatocyte growth factor (HGF), and interleukin-6 (IL-6) were measured in 67 acute liver failure patients, as well as controls. In a subset of the groups, we measured serum M-30 antigen, an exposed neoepitope from caspase cleavage. We also assessed M-30 immunoreactivity in liver tissue of ALF patients and controls. Results: Median levels for TNF-α, HGF, IL-6, and M-30 antigen were at least 10-fold greater in ALF than in hepatitis C virus or normal controls (P < .0001). Median day 1 sFas, day 3 sFas, and day 1 HGF levels varied according to etiology of acute liver failure (P = .004, P = .011, and P = .019, respectively), with values for drug-induced liver injury and acetaminophen-related ALF higher than other etiologies. Median M-30 antigen levels were significantly higher in patients who were transplanted and/or died (2183 U/L) than spontaneous survivors (1004 U/L) (P = .026). M-30 immunoreactivity in liver tissue was significantly greater in ALF patients than HCV controls (P = .004). Conclusions: TNF-α, HGF, IL-6, and M-30 antigen were significantly elevated in ALF. High levels of sFas and HGF might help to confirm a diagnosis of drug-induced liver injury or acetaminophen-related ALF. Higher levels of M-30 antigen are associated with poor clinical outcomes in ALF.

Original languageEnglish (US)
Pages (from-to)1477-1483
Number of pages7
JournalClinical Gastroenterology and Hepatology
Volume5
Issue number12
DOIs
StatePublished - Dec 2007

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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