Thématique :
- Foie
Originalité :
Très original
Solidité :
Doit faire évoluer notre pratique :
Pas encore
Nom du veilleur :
Professeur Christine SILVAIN
Coup de coeur :
  2017 Jan;65(1):202-216  
  doi: 10.1002/hep.28896  
  Polymorphisms in the IL-1 gene cluster influence systemic inflammation in patients at risk for acute-on-chronic liver failure  
  Alcaraz-Quiles J, Titos E, Casulleras M, Pavesi M, López-Vicario C, Rius B, Lopategi A, de Gottardi A, Graziadei I, Gronbaek H, Ginès P, Bernardi M, Arroyo V, Clària J  


Acute-on-chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrome characterized by acute decompensation, organ failure(s) and high short-term mortality. Recent findings suggest that an overexuberant systemic inflammation plays a primary role in ACLF progression. In this study, we examined whether genetic factors shape systemic immune responses in patients with decompensated cirrhosis. Six single-nucleotide polymorphisms (SNPs) in inflammation-related genes (interleukin [IL]-1 beta [IL-1β], rs1143623; IL-1 receptor antagonist [IL-1ra], rs4251961; IL-10, rs1800871; suppressor of cytokine signaling-3, rs4969170; nucleotide-binding oligomerization domain-containing protein 2, rs3135500; and chemerin chemokine-like receptor 1, rs1878022) were genotyped in 279 patients with cirrhosis with (n = 178) and without (n = 101) ACLF from the CANONIC study of the CLIF consortium. Among these SNPs, we identified two polymorphisms belonging to the IL-1 gene cluster (IL-1β and IL-1ra) in strong association with ACLF. Both SNPs were protective against ACLF; IL-1β (odds ratio [OR], 0.34, 95% confidence interval [CI], 0.13-0.89; P < 0.05) and IL-1ra (OR, 0.58; 95% CI, 0.35-0.95; P < 0.05) under the recessive and overdominant inheritance models, respectively. These protective SNPs translated into reduced circulating levels of IL-1β, IL-1α, IL-6, granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor, and C-reactive protein at enrollment as well as after 7-14 days of admission. These findings were confirmed in vitro in leukocytes incubated with plasma from patients with decompensated cirrhosis carrying the protective SNP genotypes. Notably, a higher frequency of the protective genotypes was observed in patients without (80%) than in those with (20%) ACLF. Consistently, patients carrying the combined protective genotypes showed a lower 28-day mortality rate.


These data identify two common functional polymorphisms in the IL-1 gene cluster, which are associated with the inflammatory process related to development of ACLF.


Question posée
Facteurs génétiques associés à la réponse immune chez les patients avec cirrhose décompensée : étude de 6 SNPs liés à l’inflammation comme l’interleukine [IL]-1 beta [IL-1β], rs1143623; antagoniste du récepteur de l’IL-1 [IL-1ra], rs4251961; IL-10, rs1800871; suppresseur du signal de cytokine-3, rs4969170…dans le cadre du CLIF.
Question posée
2 polymorphismes fonctionnels dans le cluster de gènes de l’ IL-1 sont associés à l’inflammation liée à la survenue du ACLF.

Trop tôt mais très intéressant à la fois sur la pathogénie et sur le pronostic.