title: Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.forename: Françoise
authors.initials: F
authors.lastname: Degos
authors.forename: Francoise
authors.initials: F
authors.lastname: Imbert-Bismut
authors.forename: Paul
authors.initials: P
authors.lastname: Deny
authors.forename: Paul
authors.initials: P
authors.lastname: Landais
authors.forename: Abdelkader
authors.initials: A
authors.lastname: El Hasnaoui
authors.forename: Alain
authors.initials: A
authors.lastname: Slama
authors.forename: Patrick
authors.initials: P
authors.lastname: Blin
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibault
authors.forename: Parviz
authors.initials: P
authors.lastname: Parvaz
authors.forename: Mona
authors.initials: M
authors.lastname: Munteanu
authors.forename: Christian
authors.initials: C
authors.lastname: Trepo
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D005260:Female; D005355:Fibrosis; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine