SNFGE SNFGE
 
Thématique :
- Foie
- Hépatites virales
Originalité :
Très original
Solidité :
A confirmer
Doit faire évoluer notre pratique :
Pas encore
 
 
Nom du veilleur :
Professeur Christine SILVAIN
Coup de coeur :
 
 
Gut
  2015/08  
 
  2015 Aug;64(8):1296-302  
  doi:10.1136/gutjnl-2014-307862  
 
  A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration  
 
  King LY, Canasto-Chibuque C, Johnson KB, Yip S, Chen X, Kojima K, Deshmukh M, Venkatesh A, Tan PS, Sun X, Villanueva A, Sangiovanni A, Nair V, Mahajan M, Kobayashi M, Kumada H, Lavarone M, Colombo M, Fiel MI, Friedman SL, Llovet JM, Chung RT, Hoshida Y  
  http://www.ncbi.nlm.nih.gov/pubmed/25143343  
 
 

Objective
The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression.

Design
We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1 mg/dL) and platelet count (<100 000/mm3), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years).

Results
In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child–Turcotte–Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001).

Conclusions
A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions.

 
Question posée
 
Est-ce qu’un score pronostique associant une signature génétique à la bilirubine et aux plaquettes permet de prédire la progression de l’hépatite C et la mortalité associée chez des patients cirrhotiques VHC ?
 
Question posée
 
Le score pronostique a été effectivement validé dans une cohorte indépendante de patients ayant une cirrhose débutante.
 
Commentaires

Ces résultats sont très intéressants car permettent de cibler les patients les plus à risques de décompensation ou de décès liés ou non à l’atteinte hépatique mais il faut les valider sur d’autres cohortes et trouver un moyen de financer les puces pronostiques…

 
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