Re-evaluation of the genetic cirrhosis risk score in patients with chronic hepatitis C virus infection

Aims: Recently based on a genome-wide scan, a novel "gene signature" consisting of 7 single nucleotide polymorphisms (SNPs) has been proposed to identify patients at risk for cirrhosis in chronic hepatitis C virus (HCV) infection (Huang et al. Hepatology 2007;46: 297–306). However, this cirrhosis risk score (CRS) has yet to be replicated in an independent sample. Thus, our aim now was to evaluate the gene signature in a large independent cohort of patients with chronic HCV infection.

Patients and methods: For this study, we recruited 490 German patients with chronic HCV infection. From liver biopsies, we determined the histological grades of hepatic inflammation and fibrosis according to the score system by Desmet and Scheuer. Patients were genotyped for the 7 SNPs identified by Huang et al. using PCR-based 5' exonuclease (Taqman) assays.

Results: The cohort was stratified according to the fibrosis stage in patients with mild (n=339, stage F0–F2) or advanced bridging fibrosis/cirrhosis (n=151, stage > F2). Genotyping was successful in >99% of cases. However, none of the 7 SNPs that were previously associated with cirrhosis risk showed significant differences in allele or genotype frequencies between patients with mild and advanced fibrosis in our cohort. Regression analyses did not reveal associations with inflammation or fibrosis either.

Conclusions: Despite a reasonable sample size in this validation study, we were not able to detect an association with any of the CRS SNPs. Additional studies are warranted to clarify whether the „gene signature“ is widely applicable, affected by environmental factors, or confined to certain populations.