Serum apoptosis markers in acute liver failure: a pilot study.
OBJECTIVE
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-alpha), 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-alpha, 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-alpha, 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.
Rutherford
Anna E
AE
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Hynan
Linda S
LS
Borges
Carolina B S
CB
Forcione
David G
DG
Blackard
Jason T
JT
Lin
Wenyu
W
Gorman
April R
AR
Shaikh
Obaid Shakil
OS
Reuben
Adrian
A
Harrison
Edwyn
E
Reddy
K Rajender
KR
Le
William M
WM
Chung
Raymond T
RT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D017114:Liver Failure, Acute / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D019014:fas Receptor / Q000097:blood*
D015415:Biomarkers; C491901:FAS protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D017228:Hepatocyte Growth Factor