Circulating concentrations of interleukin‐18, interleukin‐18 binding protein, and γ interferon in patients with alcoholic hepatitis

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.