The cirrhosis risk score predicts liver fibrosis progression in patients with initially mild chronic hepatitis C
Authors: Pierre Pradat, Eric Trepo, Andrej Potthoff, Rakesh Bakshi, Bradford Young, Christian Trepo, Robert Lagier, Christophe Moreno, Arnaud Lemmers, Thierry Gustot, Delphine Degre, Michael Adler, Heiner Wedemeyer
Journal: Hepatology (2009)

In a previous issue of this journal, Marcolongo et al.1 emphasized the predictive value of a genetic marker [the cirrhosis risk score (CRS)] for liver fibrosis progression in male patients with mild hepatitis C virus (HCV) infection. This article is very timely and relevant to the perplexing difficulties of managing therapy for mild hepatitis, which is present in approximately 50% of all newly diagnosed HCV cases. As recently illustrated,2 no clear recommendations are available for the management of such patients, and this is especially worrisome at this critical juncture of chronic infection when staging is most difficult. Several factors, including age, duration of infection, gender, alcohol consumption, and steatosis, are known to be associated with disease progression in patients with chronic HCV infection.3, 4 However, thus far, disease progression remains unpredictable, with known risk factors explaining only 40% of cases5; this suggests a possible role for genetic factors. Using two cohorts of patients from the Hôpital Erasme (Brussels, Belgium) and Medizinische Hochschule (Hannover, Germany), we confirmed that CRS could indeed predict fibrosis progression in patients with mild chronic hepatitis C.6 Like Marcolongo et al.,1 we found that the effect of CRS remained significant after adjustment for gender in a statistical model. Marcolongo et al. went on to observe a strong and significant association between CRS and fibrosis progression in males, but they did not find a significant association between CRS and fibrosis progression in females, although a test for interaction of CRS and gender was not significant. Indeed, we previously showed that the association between fibrosis progression and gender was strong in patients below 50 years of age (the average age for menopause) but decreased substantially above this age,7 suggesting a possible benefit of estrogens in younger women with chronic hepatitis C, probably through an antifibrogenic action8 According to a cross-sectional approach, a high CRS score was associated with an elevated risk of fibrosis, and this panel of gene variants was a better predictor than clinical factors in differentiating higher risk and lower risk for cirrhosis in HCV-infected Caucasian patients.9 New data on HCV patients with mild hepatitis suggest the potential benefit of CRS for predicting fibrosis progression. CRS-based genetic markers could therefore be of assistance in determining which patients will benefit from timely therapy and which patients, because they are at a lower risk of disease progression, can postpone treatment until improved therapies are available. Further studies of CRS and individual constituent gene variants, with a specific focus on the interaction between age and gender, will help us to better customize management strategies for optimal clinical decisions. Pierre Pradat PhD*, Eric Trepo MD , Andrej Potthoff MD , Rakesh Bakshi PhD Student , Bradford Young PhD§, Christian Trepo MD, PhD*, Robert Lagier PhD§, Christophe Moreno MD, PhD , Arnaud Lemmers MD, PhD , Thierry Gustot MD, PhD , Delphine Degre MD , Michael Adler MD, PhD , Heiner Wedemeyer MD , * Department of Hepatogastroenterology, Hotel-Dieu, Lyon, France, Department of Gastroenterology and Hepatopancreatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany, § Celera, Alameda, CA.