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).


CONCLUSIONS
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.
Liver Unit, Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Affiliated to Sackler School of Medicine, Tel Aviv, Israel. sigal001right@gmail.com
Sigal
S
Fishman
Yoav
Y
Lurie
Hava
H
Peretz
Tova
T
Morad
Elisheva
E
Grynberg
Laurie M
LM
Blendis
Moshe
M
Leshno
Eli
E
Brazowski
Guy
G
Rosner
Zamir
Z
Halpern
Ran
R
Oren
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000208:ethnology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D044465:White People / Q000235:genetics*
D019389:Cytochrome P-450 CYP2D6