A Seven-Gene Signature (Cirrhosis Risk Score) Predicts Liver Fibrosis Progression in Patients with Initially Mild Chronic Hepatitis C†

Abstract

Fibrosis progression is the main determinant of liver disease outcome in chronic hepatitis C, being influenced by environmental and host factors. Recently, a cirrhosis risk score (CRS) based on seven single-nucleotide polymorphisms was proposed as genetic predictor of cirrhosis in hepatitis C. To assess the role of CRS in predicting fibrosis progression in patients with initially no or minimal to moderate fibrosis, we investigated 271 untreated patients with chronic hepatitis C having initial liver biopsy showing METAVIR stage F0 (n = 104), F1 (n = 101), or F2 (n = 59) who had been followed up without antiviral therapies for at least 60 months (mean 108.5 +/- 71.5 months) and had a liver biopsy at the end of this observation period. Of these, 24.4% showed no histologic progression, 75.6% progressed by at least one stage, 45.0% progressed by at least two stages, and 10.3% progressed by more than two stages. The mean CRS was significantly higher (P = 0.005) in patients with fibrosis progression compared with those without progression, and this difference was particularly evident (P = 0.002) with F0 on initial biopsy. Mean CRS scores were not associated with degree of fibrosis progression. The relative risk of fibrosis progression increased with increasing CRS values. This association was significant in males but not in females and was most evident in males with F0 at initial biopsy (odds ratio 16.5, 95% confidence interval 1.6-166; P= 0.02) in the presence of high CRS. Multivariate analysis confirmed the significant association of CRS score with fibrosis progression. The predictive value of CRS was confirmed in hepatitis C virus patients admitting significant alcohol intake. Host genetics defined by CRS predict fibrosis progression in males with initially mild chronic hepatitis C and may become a useful parameter for prognostic evaluation and treatment decision.