Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C.
OBJECTIVE
While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression.


METHODS
We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models.


RESULTS
Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001).


CONCLUSIONS
This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.
Bochud
Pierre-Yves
PY
Department of Internal Medicine, Infectious Diseases Service, CHUV, Lausanne, Switzerland.
Cai
Tao
T
Overbeck
Kathrin
K
Bochud
Murielle
M
Dufour
Jean-François
JF
Müllhaupt
Beat
B
Borovicka
Jan
J
Heim
Markus
M
Moradpour
Darius
D
Cerny
Andreas
A
Malinverni
Raffaele
R
Francioli
Patrick
P
Negro
Francesco
F
D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology*; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013557:Switzerland; D013997:Time Factors; D055815:Young Adult