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

Comparison of reconstruction methods used during liver transplantation in case of a graft with replaced or accessory right hepatic artery:A retrospective study

Variations in graft arterial anatomy can increase the risk of postoperative hepatic arterial thrombosis (HAT), especially in presence of a replaced or accessory right hepatic artery (RHA). We retrospectively analyzed 223 cases of liver transplantations with the presence of an RHA on the graft. Patient outcomes were compared according to the four different reconstruction methods used: (i) the re-implantation of the RHA into the splenic or gastroduodenal artery (n = 106); (ii) the interposition of the superior mesenteric artery (SMA) (n = 83); (iii) dual anastomosis (n = 24); (iv) use of an aortic patch including the origins of both the SMA and the coeliac trunk (n = 10). A competing risk analysis and Inverse Probability Weighting (IPW) were used. We found that the interposition of the SMA method was associated with a significantly lower incidence of HAT, at 4.8% compared to the re-implantation method at 17.9%, dual anastomosis at 12.5%, and aortic patch at 20%, p =.03. In the competing risk analysis with IPW, the only risk factor for RHA thrombosis was the type of reconstruction. Taking the SMA interposition group as the reference, the sub-hazard ratio (sHR) was 5.05 (CI 95 [1.72; 14.78], p &lt;.01) for the re-implantation group, sHR = 2.37 (CI 95 [0.51; 11.09], p =.27) for the dual anastomosis group and sHR = 2.24 (CI 95 [0.35; 14.33], p =.40) for the aortic patch group. There were no differences for intraoperative transfusion, hospitalization duration (p =.37) or incidence of severe complications (p =.1). The long-term graft (p =.69) and patient (p =.52) survival was not different. In conclusion, the SMA interposition method was associated with a lower incidence of RHA thrombosis.</p

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

MIR-FEWS_data.xlsx

Clinical and biological characteristics of patients.<div><br></div

Diagnostic evaluation of hereditary hemochromatosis (HFE and non-HFE).

International audienceThe management and understanding of hereditary hemochromatosis have evolved with recent advances in iron biology and the associated discovery of numerous genes involved in iron metabolism. HFE-related (type 1) hemochromatosis remains the most frequent form, characterized by C282Y mutation homozygosity. Rare forms of hereditary hemochromatosis include type 2 (A and B, juvenile hemochromatosis caused by HJV and HAMP mutation), type 3 (related to TFR2 mutation), and type 4 (A and B, ferroportin disease). The diagnostic evaluation relies on comprehension of the involved pathophysiologic defect, and careful characterization of the phenotype, which gives clues to guide appropriate genetic testing

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

International audienc

Current medical treatment for NAFLD/NASH; [Traitement médical de la stéatohépatite métabolique en 2022]

International audienceNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The high prevalence of NAFLD is related to rising rates of obesity and metabolic syndrome. NAFLD prognosis is most closely linked with fibrosis stage, which can be assessed using non-invasive tests. Therapeutic endpoints include NASH resolution and fibrosis improvement. This hepatic endpoint must be integrated into the overall metabolic issue. Therapeutic strategy is based on lifestyle interventions and weight loss. Indeed, weight loss of 7–10% can reverse liver fibrosis, but adherence to lifestyle changes remains a major problem in real life. There are currently no approved pharmacological treatments for NASH. However, several therapeutic agents are rapidly progressing through the different phases of clinical trials. We provide a summary of recent therapeutic options with most advanced results. © 2023 Société francophone nutrition clinique et métabolisme (SFNCM

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