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Am J Gastroenterol. 2005 Sep;100(9):1970-80.

Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection.

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  • 1Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris, France.



The noninvasive serum markers, FibroTest-ActiTest (FT-AT), are an alternative to liver biopsy in patients with chronic hepatitis C and B. The aim was to use these markers in a prospective study of patients treated with lamivudine in order to assess the impact of treatment, as well as the factors associated with fibrosis progression.


Two hundred and ninety-eight patients were included in a prospective longitudinal study in 50 hospitals across France. FT-AT were measured at baseline, and then after 6, 12, and 24 months of lamivudine 100-mg treatment. Epidemiological, clinical, and virologic characteristics were analyzed by univariate and multivariate analysis.


Two hundred and eighty-three patients were included for analysis. The accuracy of FT-AT versus biopsy was validated with the area under the ROC curve, 0.77 (SE = 0.03) for bridging fibrosis and 0.75 (SE = 0.06) for severe activity (A3). At baseline, bridging fibrosis (METAVIR stages F2-F3-F4) was highly associated (p < 0.001) in multivariate analysis with male gender and age and marginally associated with anti-HBe presence (p= 0.05) and non-Asian ethnic origin (p= 0.046). Lamivudine treatment had a very significant impact overall. FT decreased significantly from 0.51 at baseline to 0.37 at 24 months (p < 0.001), and 85% of patients had improvement at 24 months. AT also decreased significantly from 0.56 to 0.13 (p < 0.0001), and 91% of patients had improvement at 24 months. A three-phase kinetics was observed for both fibrosis and activity; there was a marked improvement during the first 6 months, followed by a plateau between 6 and 12 months, and another improvement between 12 and 24 months. The occurrence of a YMDD variant does not entirely explain these three-phase variations. The first phase impact on fibrosis rates was higher in Asian patients (p= 0.01) and in patients younger than 40 yr (p < 0.001).


In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics. FT-AT should be useful in the noninvasive follow-up of lamivudine treatment.

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