Publications (3)8.94 Total impact
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Article: High rate of adefovir-lamivudine combination therapy in nucleoside-naïve patients with chronic hepatitis B in France: results of a national survey in 1730 patients.
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ABSTRACT: This study describes the types of therapy used in chronic hepatitis B (CHB) in France and patient characteristics according to therapy. This was a descriptive, multicenter, retrospective study in 1730 patients (54 centers). We collected information about demographics, epidemiology, severity of hepatitis B virus-related liver disease, antiviral therapy, response (hepatitis B viral DNA and alanine aminotransferase normalization changes), dose modification, or treatment interruption. Approximately, 60% of patients enrolled had never been treated for CHB and 33.1% were currently receiving treatment (47% first line). Of those receiving treatment, 30% were receiving adefovir-lamivudine combination. Of those receiving first-line therapy, 40, 30, and 15% were receiving lamivudine, adefovir, or adefovir-lamivudine combination, respectively. Complete and partial virological responses were seen in 59 and 13% of patients, respectively. In patients having been treated at least once, biochemical response was seen in 45%. Lamivudine or adefovir-resistant mutants were detected in 32.6 and 22.1% of patients treated by these antiviral agents, respectively. In France, among patients with CHB, we observed that one-third were receiving therapy, and, of these, 30% were receiving first-line (15%) or second-line (15%) adefovir-lamivudine combination therapy. This observation highlights that clinical practice is influenced by available scientific data on resistance induced by monotherapy.European journal of gastroenterology & hepatology 11/2010; 22(11):1290-6. · 1.66 Impact Factor -
Article: Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection.
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ABSTRACT: 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.The American Journal of Gastroenterology 09/2005; 100(9):1970-80. · 7.28 Impact Factor -
Article: A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine
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ABSTRACT: Background/Aims. Lamivudine resistance has been described in subjects with chronic hepatitis B infections, associated with mutations in the viral polymerase gene. The objective of this study was to estimate the emergence rate of lamivudine-resistant viral strains and their consequences over a two-year period. Methods. We evaluated 283 lamivudine-naive subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every six months thereafter. Viral DNA was characterised using PCR-based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. Results. The annualised incidence rate for viral polymerase mutations was 22%. The only independent risk factor identified was high viral load at inclusion. Detectable viral DNA and elevated transaminases were more frequent in subjects harbouring mutant viral strains, and these underwent a lower rate of HBe seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. Conclusions. This prospective cohort study identified lamivudine resistant mutations emerging in 22% of subjects yearly, which were apparently not associated with clinical aggravation over the study period.
