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Circulating concentrations of interleukin-18, interleukin-18 binding protein, and gamma interferon in patients with alcoholic hepatitis

Spahr, Laurent
Bresson-Hadni, Solange
Olleros, Maria
Chvatchko, Yolande
Published in Liver International. 2004, vol. 24, no. 6, p. 582-587
Abstract 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). CONCLUSION: 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.
Keywords AdultAgedAnalysis of VarianceBiological Markers/analysisCase-Control StudiesCohort StudiesDisease ProgressionFemaleGlycoproteins/analysis/*metabolismHepatitis, Alcoholic/*diagnosis/mortalityHumansIntercellular Signaling Peptides and ProteinsInterferon-gamma/analysis/*metabolismInterleukin-18/analysis/*metabolismLiver Function TestsMaleMiddle AgedPredictive Value of TestsProbabilityPrognosisReference ValuesRisk AssessmentSensitivity and SpecificitySeverity of Illness IndexStatistics, NonparametricSurvival Rate
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