Thématique :
- Carcinome hépatocellulaire (CHC)
- Hépatites virales
- Foie
Originalité :
Solidité :
Très solide
Doit faire évoluer notre pratique :
Pas encore
Nom du veilleur :
Professeur Christine SILVAIN
Coup de coeur :
  2016 Sep;64(3):720-31  
  doi: 10.1002/hep.28654  
  Progressive accumulation of mutations in the hepatitis B virus genome and its impact on time to diagnosis of hepatocellular carcinoma  
  Sung FY, Lan CY, Huang CJ, Lin CL, Liu CJ, Chen PJ, Lin SM, Yu MW  

To evaluate how hepatitis B virus (HBV) genetic variation affected progression from chronic carrier state to hepatocellular carcinoma (HCC), we analyzed HBV full-length sequences in blood obtained <1-20 years before diagnosis from 117 HCC cases and 118 controls nested in a cohort of 4,841 HBV carriers, for whom HBV genotypes B and C are predominant. The relationship between each viral single-nucleotide polymorphism (SNP) and HCC development was assessed using ordinal logistic models according to five periods of time to diagnosis (TTD). Thirty-one HBV-SNPs showed significant association with TTD after adjustment for HBV genotype, 24 of which could also be analyzed with an extended analysis on the full-length data in conjunction with 512 partial sequences (nucleotides 2,436-1,623) from the cohort. The obtained 10 robust candidate HBV-SNPs (P ≤ 0.0304), which showed odds ratios ranging from 1.89 to 8.68, were further confirmed in 163 GenBank HBV-HCC sequences from nine Asia regions, assayed after HCC diagnosis, representing the end stage of progressive hepatic diseases. The prevalence of these HBV-SNPs and their cumulative number, presented in terms of mutation score, increased with time approaching HCC diagnosis, with an odds ratio of 2.17, 4.21, 8.15, and 19.15, respectively, for the mutation score of 1, 2, 3, and ≥4 versus 0. The mutation score for predicting short-term HCC risk outperformed other factors, including HBV-DNA levels, viral genotype, and various combinations of risk factors, and revealed increasing accuracy with shorter TTD (<4.5 years before diagnosis: area under the curve = 0.83-0.89; sensitivity = 72.7%-94.1%; specificity = 58.3%-70.5%; conditioned on optimized cutoff for genotype B and C, respectively).


Identifying and tracking viral mutations is important for monitoring hepatitis B progression and early detection of HCC. (Hepatology 2016;64:720-731).

Question posée
Peut-on trouver des SNP marqueurs du risque et de l’intervalle de temps de survenue du carcinome hépatocellulaire chez des patients ayant une hépatite chronique virale B ?
Question posée
10 SNP du VHB ont été trouvés avec un score de mutation augmentant avec la date de survenue du carcinome hépatocellulaire ( OR de 2,17 à 19,15).

Certainement important de tracer les mutations du VHB pour préciser le risque de survenue du carcinome hépatocellulaire mais ces données concernant actuellement les génotypes B et C du VHB dans des populations asiatiques.