Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C☆

Received 8 February 2009; received in revised form 9 April 2009; accepted 5 May 2009. published online 08 June 2009.

Refers to article:

Forewarned is forearmed , 02 July 2009
Stefan Zeuzem
Journal of Hepatology
October 2009 (Vol. 51, Issue 4, Pages 626-627)
Full Text | Full-Text PDF (77 KB)

Background/Aims

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.

Associate Editor: J.G. McHutchison

Keywords: Hepatitis C, Fibrosis, Steatosis, Inflammation, Epidemiology

Abbreviations: HCV, hepatitis C virus, SCCS, Swiss Hepatitis C Cohort Study, BMI, body mass index, HIV, human immunodeficiency virus, ALT, alanine aminotransferase

1 Department of Internal Medicine, Infectious Diseases Service, CHUV, Lausanne, Switzerland

2 Institute of Microbiology, University of Lausanne, CHUV, Lausanne, Switzerland

3 Division of Clinical Pathology, University Hospitals, Geneva, Switzerland

4 Institute for Social and Preventive Medicine, CHUV, Lausanne, Switzerland

5 Division of Clinical Pharmacology, University Hospital, Bern, Switzerland

6 Division of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland

7 Division of Gastroenterology, Canton Hospital, St. Gallen, Switzerland

8 Division of Gastroenterology and Hepatology, University Hospital of Basel, Switzerland

9 Division of Gastroenterology and Hepatology, CHUV, Lausanne, Switzerland

10 Clinica Moncucco, Lugano, Switzerland

11 Pourtalès Hospital, Neuchâtel, Switzerland

12 Division of Hospital Preventive Medicine, CHUV, Lausanne, Switzerland

13 Division of Gastroenterology and Hepatology, University Hospitals of Geneva, 24 rue Micheli-du-Crest, 1211 Geneva, Switzerland

Corresponding author. Tel.: +41 22 3729355; fax: +41 22 3729366.

☆ The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript.

1 The members of the Swiss Hepatitis C Cohort Study Group are listed in the Appendix.

PII: S0168-8278(09)00386-9

doi:10.1016/j.jhep.2009.05.016

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