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Keywords:

  • alcoholic hepatitis;
  • cirrhosis;
  • cytokine;
  • γ interferon;
  • interleukin-18;
  • interleukin-18 binding protein

Abstract: Background: Alcoholic hepatitis (AH) is associated with dysregulated inflammatory and immune responses. interleukin-18 (IL-18), described as γ interferon (γIFN)-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, γIFN, and tumor necrosis factor α (TNF)-α 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 TNFα 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. γIFN did not differ between groups. In patients with severe and non-severe AH, IL-18, IL-18 BP, TNFα, but not γIFN, were positively correlated to DF and Child–Pugh score. Neither IL-18 nor IL-18 BP correlated to TNFα. Patients who died (n=10) during the hospitalization had higher IL-18 BP and TNFα 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 TNFα correlate to the hepatitis severity and to the degree of liver failure. High IL-18 BP and TNFα at hospital admission in non-survivors suggest it may be of prognostic value.