Mouse genetic background impacts both on iron and non-iron metals parameters and on their relationships

International audienceIron is reported to interact with other metals. In addition, it has been shown that genetic background may impact iron metabolism. Our objective was to characterize, in mice of three genetic backgrounds, the links between iron and several non-iron metals. Thirty normal mice (C57BL/6, Balb/c and DBA/2; n = 10 for each group), fed with the same diet, were studied. Quantification of iron, zinc, cobalt, copper, manganese, magnesium and rubidium was performed by ICP/MS in plasma, erythrocytes, liver and spleen. Transferrin saturation was determined. Hepatic hepcidin1 mRNA level was evaluated by quantitative RT-PCR. As previously reported, iron parameters were modulated by genetic background with significantly higher values for plasma iron parameters and liver iron concentration in DBA/2 and Balb/c strains. Hepatic hepcidin1 mRNA level was lower in DBA/2 mice. No iron parameter was correlated with hepcidin1 mRNA levels. Principal component analysis of the data obtained for non-iron metals indicated that metals parameters stratified the mice according to their genetic background. Plasma and tissue metals parameters that are dependent or independent of genetic background were identified. Moreover, relationships were found between plasma and tissue content of iron and some other metals parameters. Our data: (i) confirms the impact of the genetic background on iron parameters, (ii) shows that genetic background may also play a role in the metabolism of non-iron metals, (iii) identifies links between iron and other metals parameters which may have implications in the understanding and, potentially, the modulation of iron metabolis

Pretransplant renal function according to CKD-EPI cystatin C equation is a prognostic factor of death after liver transplantation

International audienceBackground & aims - In patients with cirrhosis, cystatin C (CystC) based equations may be more accurate indicators of glomerular filtration rate (GFR) than creatinine (Pcr) based equations. Renal function before liver transplantation (LT) is thought to impact survival after LT. We aimed at assessing pretransplant creatinine and CystC based equations with respect to their predictive value on long-term survival after LT. Methods - From 2001 to 2011, CystC was determined at pre-LT evaluation in 682 patients together with GFR assessed using MDRD-4, MDRD-6, CKD-EPI-cystatin C, CKD-EPI-creatinine and CKD-EPI-creatinine-cystatin C equations. Patients were classified according to the Kidney Disease Outcomes Quality Initiative classification (KDOQI). Results - Median age at LT was 55 [49-60] years with a median MELD score of 13.5 [8.3-19.2] and a median post-transplant follow-up of 60 [26-89] months. Using CKD-EPI Cystatin C and the KDOQI classification, 21.1% of patients were stage 1, 43.1% stage 2, 29.1% stage 3 and 6.5% stage 4. Kaplan-Meier survival estimates were significantly different between KDOQI stages when determined using the CKD-EPI-CystatinC equation. This was not the case when using the other equations. At multivariate analysis, GFR and KDOQI estimated using the CKD-EPI-CystatinC equation were significantly associated with death (HR: 0.992; CI95%: 0.986-0.999 and 1.24; CI95%: 1.02-1.50 respectively). When assessed using the MDRD-4, MDRD-6, CKD-EPI-Creatinine-CystatinC and CKD-EPI-Creatinine equations GFR was not significantly associated with death. Conclusions - Estimated pre-LT renal function is predictive of post-LT survival only when assessed using the CKD-EPI cystatin C equation. This supports the use of Cystatine C and of its related equation for the assessment of renal function before liver transplantation

Therapeutic anticoagulation after liver transplantation is not useful among patients with pre-transplant Yerdel-grade I/II portal vein thrombosis:A two-center retrospective study

BACKGROUND: Portal vein thrombosis (PVT) is no longer a contraindication for liver transplantation (LT). While therapeutic anticoagulation (tAC) is recommended during the waiting period, there is no evidence for its usefulness in the prevention of PVT recurrence after LT. OBJECTIVES: The aim of our study was to evaluate the role of tAC post-LT in the prevention of PVT recurrence. PATIENTS/METHODS: All adult LTs performed in 2 high volume centres between 2003 and 2018, were retrospectively analysed. Only patients with PVT classified as Yerdel grade I or II and with standard portal reconstruction were included. PVT recurrence and tAC-associated morbidity within 1 year were compared between patients receiving tAC or not. RESULTS: During the study period, out of 2612 LTs performed, 235 (9%) patients with PVT were included. 113 patients (48.1%) received post-LT tAC (tAC group) while 122 (51.9%) did not (non-tAC group). The incidence of bleeding events was significantly higher in the tAC group (26 (23%) vs. 5 (4.1%), p<0.01) and the initial hospitalization duration was longer (21 vs. 17.5 days, p<0.01). Within the first year, PVT recurrence was observed for 9 (3.8%) patients without any difference between the tAC and non-tAC groups (6 (5.1%) vs. 3 (2.5%), p=0.39). The only identified risk factor for PVT recurrence was the recipients' age (OR=0.94, p=0.03). Graft (p=0.11) and patient (p=0.44) survival were similar between the 2 groups. CONCLUSION: Therapeutic anticoagulation is not necessary in the prevention of grade I/II PVT recurrence and is associated with higher morbidity and longer hospital stay

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Recurrence of primary biliary cholangitis after liver transplantation Is Tacrolimus really worse than other drugs?

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Comparaison de la prévalence de l'hépatite B occulte chez des patients "anti-HBc isolé" dans une population française à risque et africaine

L'hépatite B occulte est définie par la présence d'ADN du VHB en l'absence de l'antigène Hbs. Sa prévalence semble liée à celle de l'hépatite B mais la variabilité des techniques utilisée rend la comparaison entre étude difficile. Le but de cette étude était de comparer la prévalence de l'hépatite B occulte chez des patients anti-Hbc isolés dans deux populations avec la même technique. La population française était constituée de 1375 patients ayant eu une sérologie et une charge virale du VHB et la population africaine de 421 volontaires. L'ADN du VHB était recherché avec le test COBAS Amplicor HBV Monitor (Roche). La prévalence de l'anticorps anti-Hbc dans les populations française et africaine était respectivement de 69% et 82%. Une hépatite B occulte était retrouvé chez 1/96 (1,04%) patients français et chez 19/91 (20,21 %) patients africains. Dans notre étude la prévalence de l'hépatite occulte est plus importante dans la population africaine par rapport à la population française.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Reply to: Reduced mortality due to phlebotomy in moderately iron-loaded HFE Haemochromatosis? The need for clinical trials.

International audienceReply to: Reduced mortality due to phlebotomy in moderately iron-loaded HFE Haemochromatosis? The need for clinical trials. 10.1016/j.jhep.2015.03.028Original article: Decreased cardiovascular and extrahepatic cancer-related mortality in treated patients with mild HFE hemochromatosis (10.1016/j.jhep.2014.10.025) https://hal-univ-rennes1.archives-ouvertes.fr/hal-01091479

Kinase inhibitors in the treatment of chronic hepatitis C virus.

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