Polymorphismes du gène ABCB1 (MDR1) et impacts fonctionnels dans le transport de xénobiotiques - Particularités chez les sujets Noirs Subsahariens

Les différences interindividuelles observées dans la réponse aux médicaments sont en partie dues aux polymorphismes du gène ABCB1 codant pour la glycoprotéine-P (P-gp), une protéine de transport des médicaments. Cette revue a pour but de faire le point des connaissances sur les polymorphismes du gène ABCB1, leur relevance fonctionnelle et clinique et de préciser les particularités au sein de la population noire subsharienne. Le rôle du gène (ABCB1)MDR1 dans la variabilité pharmacocinétique ou pharmacodynamique a été démontrée clairement in vitro, dans des modèles animaux et lors d’études cliniques. Le polymorphisme C3435T est associé à une diminution de l’expression protéique de la P-gp et, par voie de conséquence, de son activité. L’existence d’une forte association entre les polymorphismes C3435T et G2677T a suggéré alors que la différence fonctionnelle observée peut être attribuée également au deuxième polymorphisme i.e le G2677T (exon 21). Il a été identifié chez les noirs africains de nouveaux polymorphismes et des haplotypes particuliers. Différnts travaux ont démontré également que le gène ABCB1 intervient dans le suivi thérapeutique des patients mis sous immunosuppresseurs, anticancéreux, antidépresseurs, antirétroviraux ou antihypertenseurs. Des perspectives fort intéressantes en pharmacothérapie avec entre autres l’utilisation de modulateurs de la P-gp sont d’actualité.Mots clés: Pharmacogénétique, glycoprotéine-P, médicaments, substances exogènes, Noirs Subsaharien

A simple hepatic cyst with elevated serum and cyst fluid CA19-9 levels: a case report

<p>Abstract</p> <p>Introduction</p> <p>Simple hepatic cysts rarely cause symptoms, however, occasionally they become symptomatic due to mass effect, rupture, hemorrhage, and infection. We report a patient with a large hepatic cyst with elevated serum and cyst fluid CA19-9 levels. We studied serum and cyst fluid CA19-9 levels in this patient, before and after the intracystic instillation of minocycline hydrochloride.</p> <p>Case presentation</p> <p>A 76-year-old Japanese woman was diagnosed as having an infected hepatic cyst, by physical examination and enhanced abdominal computed tomography. Serum (170 U/ml; reference: < 37 U/ml) and hepatic cyst fluid (371 U/ml) CA19-9 levels were elevated. After the intracystic instillation of minocycline hydrochloride, necrotic cells in the cyst were drained, and it totally collapsed after 1 week. Cyst fluid CA19-9 levels increased remarkably after the intracystic instillation of minocycline hydrochloride, while serum CA19-9 levels decreased significantly.</p> <p>Conclusion</p> <p>Our study is the first report to reveal the influence of intracystic instillation of minocycline hydrochloride on serum and cyst fluid CA19-9 levels in a patient with a simple hepatic cyst.</p

Effectiveness and tolerability of pegylated interferon alfa-2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust Study

Background and study aims : Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community-based trial evaluating the sustained virological response. Patients and Methods : Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 mu g/kg/wk) and weight. based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. Results : In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91(41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). Conclusion : Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community-based clinical practice. (Ada gastroenterol. belg., 2010, 73, 5-11)

Immunisation after hepatitis B polyvalent vaccination among children in South Kivu Province Democratic Republic of the Congo

Background. The World Health Organization recommends the integration of vaccination against hepatitis B virus (HBV) into the national immunisation programmes of all highly endemic countries. Protective efficacy, defined as a hepatitis B surface antibody (HBsAb) level ≥10 mIU/mL, is ideally obtained in &gt;90 - 95% of immunised children. The Democratic Republic of the Congo (DRC) implemented this recommendation in 2007 by introducing administration of hepatitis B vaccine in a combined formulation.Objectives. To assess the rate of seroprotection in children who received hepatitis B vaccine in the DRC context.Methods. This descriptive cross-sectional study was conducted during routine postnatal consultations at the General Hospital of Bukavu in South Kivu Province, DRC. A total of 200 infants aged 6 - 12 months and their mothers were consecutively enrolled. All the infants received the three-dose regimen of hepatitis B vaccine 6, 10 and 14 weeks after birth. The mothers were tested for hepatitis B surface antigen and HIV, while HBsAb levels were measured in the infants to determine immune response.Results. Seroprotection was achieved in 84.5% of the infants. No maternal (age, parity, duration of pregnancy, HIV and HBV status) or infant (sex, weight at birth) factors were found to be associated with absence of immunological response.Conclusions. The study demonstrated that the rate of seroprotection in the current vaccination programme against HBV in DRC was lower than desirable but comparable to rates reported in some other African countries. Further studies are needed to assess this finding and to evaluate ways to optimise the seroprotection rate.Â

Oligofructose Promotes Satiety in Healthy Human: A Pilot Study.

Objective: The administration of a fermentable dietary fibre (oligofructose) in rats increases satietogenic gut peptides and lowered spontaneous energy intake. The aim of the study was to assess the relevance of those effects of oligofructose on satiety and energy intake in humans. Design: Single-blinded, crossover, placebo-controlled design, pilot study. Subjects: Volunteers included five men and five women aged 21-39 years, BMI ranging from 18.5 to 27.4 kg/m 2 , were randomly assigned as described below. Interventions: Subjects were included in two 2-week experimental phases during which they received either fibre (oligofructose (OFS)) or placebo (dextrine maltose (DM)); a 2-week washout period was included between crossover phases. In total, 8 g OFS or 8 g DM were ingested twice daily (16 g/day in total). Energy intake, hunger, satiety, fullness and prospective food consumption were assessed with analogue scales at the end of each experimental phase. Results: During breakfast, OFS significantly increases the satiety (P ¼ 0.04) without any difference on other sensations as compared to DM treatment periods. After lunch, no significant differences are observed between treatment period. At dinner, OFS significantly increases satiety (P ¼ 0.04), reduces hunger (P ¼ 0.04) and prospective food consumption (P ¼ 0.05). The energy intake at breakfast and lunch are significantly lower (P ¼ 0.01, 0.03, respectively) after OFS treatment than after DM treatment. Total energy intake per day is 5% lower during OFS than in DM period. Conclusion: Oligofructose treatment increases satiety following breakfast and dinner, reduces hunger and prospective food consumption following dinner. This pilot study presents a rationale to propose oligofructose supplements in the management of food intake in overweight and obese patients. Sponsorship: This project is supported by an FSR grant from the Université catholique de Louvain

Immunisation after hepatitis B polyvalent vaccination among children in South Kivu Province, Democratic Republic of the Congo

Background. The World Health Organization recommends the integration of vaccination against hepatitis B virus (HBV) into the national immunisation programmes of all highly endemic countries. Protective efficacy, defined as a hepatitis B surface antibody (HBsAb) level ≥10 mIU/mL, is ideally obtained in &gt;90 - 95% of immunised children. The Democratic Republic of the Congo (DRC) implemented this recommendation in 2007 by introducing administration of hepatitis B vaccine in a combined formulation.Objectives. To assess the rate of seroprotection in children who received hepatitis B vaccine in the DRC context.Methods. This descriptive cross-sectional study was conducted during routine postnatal consultations at the General Hospital of Bukavu in South Kivu Province, DRC. A total of 200 infants aged 6 - 12 months and their mothers were consecutively enrolled. All the infants received the three-dose regimen of hepatitis B vaccine 6, 10 and 14 weeks after birth. The mothers were tested for hepatitis B surface antigen and HIV, while HBsAb levels were measured in the infants to determine immune response.Results. Seroprotection was achieved in 84.5% of the infants. No maternal (age, parity, duration of pregnancy, HIV and HBV status) or infant (sex, weight at birth) factors were found to be associated with absence of immunological response.Conclusions. The study demonstrated that the rate of seroprotection in the current vaccination programme against HBV in DRC was lower than desirable but comparable to rates reported in some other African countries. Further studies are needed to assess this finding and to evaluate ways to optimise the seroprotection rate.

Effectiveness and tolerability of pegylated interferon alfa2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust study

Background and study aims : Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community based trial evaluating the sustained virological response. Patients and Methods : Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 μg/kg/wk) and weight-based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. Results : In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91 (41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). Conclusion : Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community- based clinical practice

P73 Preliminary results of the Study of Acute Liver Transplant (SALT): NSAID exposure and risk of acute liver failure leading to transplantation in 7 European countries

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Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study was supported by a Grant core funding from the Agency for Science Technology and Research (A*STAR, Singapore) and a Singapore Translational Research Investigator Award (NRMC/StaR/013/2012) to AB as well as NIHR Biomedical Centre, Oxford, WT 091663MA, NIAID1U19AI082630-01, Oxford Martin School funding and an NIHR Senior Investigator award to PK