Role of CYP2D6 polymorphism in predicting liver fibrosis progression rate in Caucasian patients with chronic hepatitis C

Objective: Previous studies have demonstrated that CYP2D6 polymorphism is associated with liver cirrhosis. The aim of the present study was to find out whether CYP2D6*4, the poor metabolizer allele can predict fibrosis progression rate. Methods: Seventy-five Caucasian patients with chronic hepatitis C infection were recruited. They were divided into two groups, 'fast fibrosers' and 'slow fibrosers', according to Poynard's fibrosis progression curves. Sixty-two patients underwent liver biopsy. Twenty healthy neonates were included as control population. DNA was extracted from peripheral blood and CYP2D6*4 was tested by polymer chain reaction using fluorescent hybridization probes in a lightCycler instrument. Results: Forty-two patients were classified as 'fast fibrosers' and 33 patients as 'slow fibrosers'. The frequency of CYP2D6*4 allele in the 'fast fibrosers' (34.5%) was significantly higher compared with the 'slow fibrosers' (15%) (P value = 0.007). There was no significant difference between the frequency of CYP2D6*4 in the 'slow fibrosers' (15%) compared with the controls (12.5%). Carrier state of CYP2D6*4 was the only covariate that was significantly positively correlated with fast progression to cirrhosis (odds ratio = 6.5, P = 0.01). Conclusion: This study indicates for the first time that CYP2D6 genotype might be a significant predictor of liver fibrosis progression rate in chronic hepatitis C patients.