Alain Slama

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

OBJECTIVES: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.

A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine

Summary.  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 2‐year period. We evaluated 283 lamivudine‐naïve subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every 6 months thereafter. Viral DNA was characterized using polymerase chain reaction (PCR)‐based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. The annualized 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 hepatitis B e seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. 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.

Improvement in quality of life after initiation of lamotrigine therapy in patients with epilepsy in a naturalistic treatment setting

Quality of life is impaired in patients with epilepsy and can be improved by effective therapy. Randomised clinical trials have shown that lamotrigine treatment is associated with improved quality of life. However, little information is available on quality of life or treatment effects in patients with epilepsy in the general population. The objective of this study was to estimate the impact of lamotrigine on quality of life in a naturalistic treatment setting. The study included adult patients with epilepsy in whom lamotrigine therapy was initiated. Each subject completed the Quality of Life in Epilepsy Inventory (QOLIE)-31 quality of life questionnaire at inclusion and at a follow-up visit in the next 4 months. Demographic information and medical history were provided by the investigator. These were evaluated as potential determinants of change in quality of life using logistic regression. Three hundred and forty-one patients were evaluated, 192 starting lamotrigine in combination with another drug, 90 as a first-line monotherapy, 45 as a switch from another drug and 14 as a reduction to monotherapy from a previous combination. Baseline scores on the QOLIE-31 ranged from 53.8 in the combination group to 69.5 in the first-line group. 34.6% of patients were considered to be responders, with no significant differences between treatment regimen. Most improvement was seen for the energy-fatigue and medication effects subscales and, for the first-line group, seizure worry. Seizure type was the only determinant of improvement of quality of life identified. In conclusion, lamotrigine treatment is associated with improved quality of life, regardless of treatment regimen.

La migraine en pharmacie d’officine : une étude multi-centrique française

Migraine remains an under-diagnosed disease. Many migraine sufferers are not currently treated within the healthcare system and most of them take self-medication. A prospective national study was conducted in France with 770 pharmacies. Data on symptoms, drug dispensing, patient management, and satisfaction of 7 264 subjects complaining of headache at the pharmacy were collected. Two-third of the subjects were migraine sufferers according to the IHS criteria. 32 p. cent of them came to the pharmacy during a pain attack. 63 p. cent had a medical prescription (46 p. cent in the non-migraine group) with triptans being most often prescribed drug (in almost half of the cases). Nearly one-third of the migraine sufferers without medical prescription were referred to a doctor by the pharmacist. This first study on migraine and headaches and pharmacies highlights the important role that pharmacists can play in improving the management of migraine and headache through advice and proper orientation towards medical practitioners.