Circulating concentrations of interleukin-18, interleukin-18 binding protein, and gamma interferon in patients with alcoholic hepatitis.
BACKGROUND
Alcoholic hepatitis (AH) is associated with dysregulated inflammatory and immune responses. interleukin-18 (IL-18), described as gamma interferon (gammaIFN)-inducible factor, and its natural antagonist, IL-18 binding protein (IL-18 BP), has not been fully studied in patients with AH. Thus, our aim was: (i) to determine plasma values of IL-18, IL-18 BP, gammaIFN, and tumor necrosis factor alpha (TNF)-alpha in patients hospitalized for biopsy-proven AH; (ii) to correlate these cytokines with the severity of AH, as assessed by Maddrey's discriminant function (DF), the degree of liver failure using the Child-Pugh score and blood neutrophils; (iii) to compare cytokines values in survivors and non-survivors.


METHODS
Cytokines were measured using specific immunoassays within 7 days of admission. The diagnosis of AH was based on histology in all cases. We studied 43 cirrhotic patients with a Maddrey's DF>/=32 (severe AH), 29 patients with a score <32 (non-severe AH), 12 patients with abstinent alcoholic cirrhosis, and 10 healthy subjects.


RESULTS
IL-18 and TNFalpha were increased in severe AH as compared with healthy subjects. Plasma IL-18 BP was elevated in patients with severe and non-severe AH as compared with healthy subjects. gammaIFN did not differ between groups. In patients with severe and non-severe AH, IL-18, IL-18 BP, TNFalpha, but not gammaIFN, were positively correlated to DF and Child-Pugh score. Neither IL-18 nor IL-18 BP correlated to TNFalpha. Patients who died (n=10) during the hospitalization had higher IL-18 BP and TNFalpha at admission as compared with survivors (322 [172-504] vs 222 [109-441] ng/ml; 7.5 [2.2-17.3] vs 3 [0.6-20] pg/ml, P<0.01, respectively).


CONCLUSIONS
In cirrhotic patients with AH, IL-18, IL-18 BP, and TNFalpha correlate to the hepatitis severity and to the degree of liver failure. High IL-18 BP and TNFalpha at hospital admission in non-survivors suggest it may be of prognostic value.
Spahr
Laurent
L
Gastroenterology and Hepatology Unit, Geneva, Switzerland. Laurent.Spahr@hcuge.ch
Garcia
Irène
I
Bresson-Hadni
Solange
S
Rubbia-Brandt
Laura
L
Guler
Reto
R
Olleros
Maria
M
Chvatchko
Yolande
Y
Hadengue
Antoine
A
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism*; D006519:Hepatitis, Alcoholic / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D020382:Interleukin-18 / Q000032:analysis / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate
D015415:Biomarkers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein; D007371:Interferon-gamma