Observation du changement social et culturel

S’est constituée à l’université Lyon 2 une équipe de recherches largement pluridisciplinaire, dont les objectifs sont de s’interroger sur les méthodes d’observation continue du changement social et culturel (en collaboration avec d’autres équipes régionales). Les textes présentés ici ne sont pas encore des résultats, mais ils présentent les terrains qui ont été retenus par les chercheurs lyonnais, et qui sont aujourd’hui objets d’enquêtes et d’études

Tacrolimus Concentrations Measured in Excreted Bile in Liver Transplant Recipients The STABILE Study

International audiencePurpose - Tacrolimus (TAC) is the main immunosuppressive drug in liver transplantation. Despite intensive therapeutic drug monitoring (TDM) that relies on whole blood trough concentration (TAC), patients still present with acute cellular rejection or TAC-related toxic effects with concentrations within the therapeutic range. TAC concentration in peripheral blood mononuclear cells (TAC) is considered as an efficient surrogate marker of TAC efficacy. However, it is still not applicable in daily practice. New TDM methods are therefore needed, especially during the early postoperative period. TAC is metabolized in the liver and eliminated through biliary excretion. We therefore hypothesised that TAC concentration measured in excreted bile (TAC) could be a relevant surrogate marker of its efficacy. Methods - The Therapeutic Drug Monitoring of Tacrolimus Biliary Concentrations for Liver-Transplanted Patients (STABILE) study is a prospective monocentric trial. During the 7 first days after TAC therapy initiation, TAC was measured. The correlation between TAC and TAC as well as between TAC and TAC was assessed. The correlations between TAC and liver graft function parameter or with occurrence of neurologic toxic effects were also evaluated. Findings - Between May 2016 and April 2017, 41 patients were analyzed. TAC was significantly correlated with TAC (r = 0.25, P = 0.007). However, a better correlation was found between TAC and TAC (r = 0.53, P < 0.001) and was confirmed in multivariate analysis. However, only TAC was significantly correlated with liver graft function, such as factor V (r = 0.40, P = 0.009) or bilirubin level (r = 0.21, P = 0.01), and significantly lower in patients presenting with neurologic toxic effects (P < 0.001). Receiver operating characteristic curve analysis found that a TAC level lower than 0.20 ng/mL on day 2 after TAC therapy initiation was a good predictive marker of occurrence of neurotoxic effects (AUC = 0.81). Implications - TAC is not a better surrogate maker of TAC activity than TAC. However, TAC could help predict the occurrence of TAC toxic effects when a T-tube is inserted. ClinicalTrials.gov identifier: NCT02820259

Tacrolimus Concentrations Measured in Excreted Bile in Liver Transplant Recipients The STABILE Study

International audiencePurpose - Tacrolimus (TAC) is the main immunosuppressive drug in liver transplantation. Despite intensive therapeutic drug monitoring (TDM) that relies on whole blood trough concentration (TAC), patients still present with acute cellular rejection or TAC-related toxic effects with concentrations within the therapeutic range. TAC concentration in peripheral blood mononuclear cells (TAC) is considered as an efficient surrogate marker of TAC efficacy. However, it is still not applicable in daily practice. New TDM methods are therefore needed, especially during the early postoperative period. TAC is metabolized in the liver and eliminated through biliary excretion. We therefore hypothesised that TAC concentration measured in excreted bile (TAC) could be a relevant surrogate marker of its efficacy. Methods - The Therapeutic Drug Monitoring of Tacrolimus Biliary Concentrations for Liver-Transplanted Patients (STABILE) study is a prospective monocentric trial. During the 7 first days after TAC therapy initiation, TAC was measured. The correlation between TAC and TAC as well as between TAC and TAC was assessed. The correlations between TAC and liver graft function parameter or with occurrence of neurologic toxic effects were also evaluated. Findings - Between May 2016 and April 2017, 41 patients were analyzed. TAC was significantly correlated with TAC (r = 0.25, P = 0.007). However, a better correlation was found between TAC and TAC (r = 0.53, P < 0.001) and was confirmed in multivariate analysis. However, only TAC was significantly correlated with liver graft function, such as factor V (r = 0.40, P = 0.009) or bilirubin level (r = 0.21, P = 0.01), and significantly lower in patients presenting with neurologic toxic effects (P < 0.001). Receiver operating characteristic curve analysis found that a TAC level lower than 0.20 ng/mL on day 2 after TAC therapy initiation was a good predictive marker of occurrence of neurotoxic effects (AUC = 0.81). Implications - TAC is not a better surrogate maker of TAC activity than TAC. However, TAC could help predict the occurrence of TAC toxic effects when a T-tube is inserted. ClinicalTrials.gov identifier: NCT02820259

Covid-19 in liver transplant recipients: the French SOT COVID registry

International audienceBackground: Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry-based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19.Methods: COVID-19 was diagnosed in patients who had a positive PCR assay for SARS-CoV-2 or in presence of typical lung lesions on imaging or specific SARS-CoV-2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded.Results: Of the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children). Hospitalized patients had a median age of 65.2 years (IQR: 58.1 - 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3%), hypertension (61.2%), diabetes (50.7%), cardiovascular disease (20.9%) and respiratory disease (16.4%). SARS-CoV-2 infection was identified after a median of 92.8 months (IQR: 40.1 - 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30-day mortality rate was 20.0%, and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality.Conclusion: In our large nationwide study, Covid-19 in LT recipients was associated with a high mortality rate

Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors

International audienceBackground and aim: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. Approach and results: Retrospective multicentre analysis of liver disease (transaminases>30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n=1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease (PSVD) in 48%, and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and hepatocellular carcinoma occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group (80/396, (20%)), OR 12.9 (CI95% 7.8-21.3, p <0.001). Conclusions: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild they may be associated with severe disease. PSVD and cirrhosis were the most frequent lesions suggesting that the mechanism of action is multifactorial