14 results on '"Canivet, Clémence M."'
Search Results
2. Hépatites sexuellement transmissibles.
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Laveissiere, Juliette, Canivet, Clémence M., Ollier, Laurence, Cua, Eric, and Anty, Rodolphe
- Abstract
Résumé: Certaines pratiques sexuelles telles que le chemsex (usage de substances psychoactives pour booster ses performances et sensations sexuelles) ou les plans slam (mêmes objectifs que le chemsex mais en utilisant des substances injectées en intraveineuse), notamment dans la population des hommes ayant des relations sexuelles avec des hommes (HSH), favorisent les infections sexuellement transmissibles (IST). La transmission sexuelle de l'hépatite B se fait principalement par les fluides sexuels (sperme, sécrétions vaginales) et la salive tandis que l'hépatite C se transmet principalement lors de pratiques sexuelles traumatiques entraînant une effraction muqueuse. Le virus de l'hépatite A étant excrété dans les selles, se transmet via des pratiques oro-anales. L'épidémie européenne d'hépatite A de 2016-2017 a touché les HSH présentant des facteurs de risque tels que des partenaires sexuels anonymes multiples, des relations sexuelles en groupe, et des pratiques oro- et digito-anales. D'autres virus transmis par contact sexuel ou via la salive (cytomégalovirus, Epstein-Barr Virus ou Herpes Simplex Virus) peuvent occasionner des hépatites plus souvent symptomatiques chez des patients fragiles (femmes enceintes ou immunodéprimés). Les modes de détection de ces infections s'appuient sur des tests biologiques indirects (sérologie) et directs (détection du génome et de l'antigène). Les hépatites A et B aiguës sont à déclaration obligatoire. Des moyens de prévention existent en fonction du type de transmission. La vaccination contre l'hépatite A est recommandée pour les HSH ou les individus ayant des pratiques oro-anales. L'usage du préservatif, de seringues et de pailles à usage unique lors des plans chemsex et slam sont des mesures préventives générales des IST. Enfin, la PrEP ou prophylaxie préexposition est un moyen de prévention de la transmission du VIH, voire du VHB et partiellement de l' Herpes virus. High risk sexual practices among men who have sex with men (MSM) are important route of sexually transmitted infections (STI). Transmission of hepatitis B is mainly through sexual fluids (sperm and vaginal secretions) and saliva, while hepatitis C is mainly transmitted through violent sexual practices leading to mucosal break-in. The hepatitis A virus, being excreted in the stool, is transmitted via oro-anal practices. The 2016-2017 European epidemic of hepatitis A has affected MSM with risk factors such as anonymous sexual partners, group sex, and oral and digito-anal practices. Other viruses transmitted by sexual contact or via saliva (Cytomegalovirus, Epstein-Barr Virus or Herpes Simplex Virus) can cause hepatitis, most often in fragile patients (pregnant women or immunosuppressed patients). The detection methods are based on indirect (serological) and direct (genome and antigen detection) biological tests. Acute Hepatitis A and B must be notified. Prevention depends on the type of transmission. Vaccination against hepatitis A is recommended for MSM or those with oro-anal practices. The use of single-use condoms, syringes, and straws in the chemsex and slam are general preventative measures. Finally, pre-exposure prophylaxis (PrEP) is a means of preventing HIV transmission and eventually HBV and Herpes virus. [ABSTRACT FROM AUTHOR]
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- 2019
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3. Stéatoses hépatiques métaboliques : histoire naturelle, physiopathologie et démarche diagnostique.
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Anty, Rodolphe, Canivet, Clémence M., Gual, Philippe, and Tran, Albert
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Non-alcoholic fatty liver disease (NAFLD) is a major health problem which is now recognized by governmental agencies. NAFLD is a spectrum of diseases including non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH) and its complications: fibrosis, cirrhosis and hepatocellular carcinoma. Worldwide, 25% of the general population have NAFL, and 1.5 to 6.5% have NASH. These high frequencies are linked to the epidemic of overweight and obesity. As for obesity, NAFLD is a complex and heterogeneous disease. The mechanisms, the clinical occurrence, the associated diseases and the natural history imply multiple genetic and environmental factors. Insulin-resistance may play a central but not exclusive role in the occurrence of NASH. NAFLD such as obesity and type 2 diabetes is a multisystem disease associated with various complications (cardio-vascular events, hepatic and extra hepatic cancers, chronic kidney disease. . .). Advances in the knowledge of the mechanisms of NAFLD led to the development of new pharmacological or non pharmacological treatments, which are undergoing clinical trials. The management of patients with NAFLD must be well structured, particularly because the liver biopsy, which is still the gold standard, cannot be performed in all suspected subjects. There is a need to develop and validate new non-invasive tools based on analyses of serum or on physical assessment that allow reliable assessment of fibrosis, the NASH and steatosis. Their availability will allow easy screening, diagnosis and follow-up of patients. [ABSTRACT FROM AUTHOR]
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- 2017
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4. Génétique et épigénétique dans la non-alcoholic fatty liver disease.
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Canivet, Clémence M., Tran, Albert, Gual, Philippe, and Anty, Rodolphe
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Non-Alcoholic Fatty Liver Disease (NAFLD) is a spectrum of liver diseases that encompass steatosis, Non-Alcoholic Steatohepatitis (NASH) and fibrosis. It is a major public health problem due to its frequency and potential complications (cirrhosis, hepatocellular carcinoma). At present, the monitoring of patients with steatosis or NASH is not fully coded and current treatments are not very effective. Research into the genetics and epigenetics of NAFLD is booming. While genetics studies modifications into the nucleotide sequence of genes, epigenetics studies modifications in the function of a gene that cannot be explained by alterations to the gene sequence. PNPLA3, TM6SF2 and MBOAT7-TMC4 are the 3 main genes for which single nucleotide polymorphisms are associated with steatosis, NASH and hepatic fibrosis, independently of insulin resistance and metabolic syndrome. MicroRNAs (miR), small non-coding RNAs inhibit messenger RNAs and thus regulate gene expression. The expression of some miRs in the liver is modified in NAFLD: miR 122 is decreased and miR 34a is increased. Some miRs are also found in the circulation: for example, miR 122 is increased in the case of NAFLD. Finally, the methylation of target genes is modified in NAFLD resulting in changes in their expression. This is particularly the case for PPAR, a key gene for lipid metabolism. In future, it is likely that substantial genetic and epigenetic data can be obtained for each individual from a simple blood sample allowing personalized monitoring and treatment for NAFLD, as for other diseases. [ABSTRACT FROM AUTHOR]
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- 2017
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5. Severe Vitamin D Deficiency May be an Additional Cofactor for the Occurrence of Alcoholic Steatohepatitis.
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Anty, Rodolphe, Canivet, Clémence M., Patouraux, Stéphanie, Ferrari‐Panaia, Patricia, Saint‐Paul, Marie Christine, Huet, Pierre‐Michel, Lebeaupin, Cynthia, Iannelli, Antonio, Gual, Philippe, and Tran, Albert
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COMPLICATIONS of alcoholism , *FIBROSIS , *BIOLOGICAL assay , *BIOPSY , *CHI-squared test , *CONFIDENCE intervals , *FATTY liver , *RESEARCH funding , *T-test (Statistics) , *VITAMIN D , *VITAMIN D deficiency , *LOGISTIC regression analysis , *CROSS-sectional method , *DESCRIPTIVE statistics , *ODDS ratio , *MANN Whitney U Test , *DISEASE complications , *DIAGNOSIS - Abstract
Background Among its pleiotropic effects, vitamin D may protect the liver from fibrosis and/or inflammation. However, the impact of vitamin D on liver pathology in hepatitis C remains unclear, and very few studies including alcoholic patients with liver pathologies have been performed. Here we compared the levels of 25- OH vitamin D in the blood of alcoholic patients with the occurrence of alcoholic steatohepatitis (ASH) or bridging fibrosis. Methods One hundred and one alcoholic patients were included. All the patients received a liver biopsy, and the levels of 25- OH vitamin D were evaluated with the Liaison 25-OH vitamin D assay. Logistic regression analyses were performed to obtain predictive factors of liver histology. Results Among alcoholic patients, 40.6% presented ASH and 39.6% presented bridging fibrosis. A severe deficiency in 25-OH vitamin D (<10 ng/ml) was seen in 60.4% of patients. This deficiency was frequent in patients with ASH (85.4%) and in those with bridging fibrosis (80%) but was independently associated only with ASH (odds ratio = 8.46 [95% confidence interval 2.05 to 34.89], p = 0.003). Conclusions In alcoholic patients, a severe deficiency in 25- OH vitamin D was independently associated with the occurrence of ASH. [ABSTRACT FROM AUTHOR]
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- 2015
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6. Investigation of Inherited Chromosomally Integrated Human Herpesvirus-6A+ and -6B+ in a Patient with Ulipristal Acetate-Induced Fulminant Hepatic Failure.
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Izquierdo, Laure, Canivet, Clémence M., De Martin, Eleonora, Antonini, Teresa M., Roque-Afonso, Anne-Marie, Coilly, Audrey, and Deback, Claire
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LIVER failure , *DRUG side effects , *PROGESTERONE , *PROGESTERONE receptors , *HEREDITY , *HAIR follicles , *HUMAN herpesvirus-6 - Abstract
Inherited chromosomally integrated (ici) human herpes virus 6 (HHV-6) is estimated to occur in 0.6–2.7% of people worldwide. HHV-6 comprises two distinct species: HHV-6A and HHV-6B. Both HHV-6A and HHV-6B integration have been reported. Several drugs are capable of activating iciHHV-6 in tissues, the consequences of which are poorly understood. We report herein a case of a woman with iciHHV-6A+ and iciHHV-6B+, who developed ulipristal acetate (a selective progesterone receptor modulator)-induced fulminant hepatic failure that required liver transplantation. We confirmed the presence of ~one copy per cell of both HHV-6A and HHV-6B DNA in her hair follicles using multiplex HHV-6A/B real-time PCR and demonstrated the Mendelian inheritance of both iciHHV-6A and iciHHV-6B in her family members over three generations. Because of the rarity of this presentation, we discuss herein the possible links between reactivated HHV-6 from iciHHV-6A and/or iciHHV-6B and adverse drug reactions, suggesting that iciHHV-6 could be screened before the introduction of any hepatotoxic drugs to exclude HHV-6 active disease or combined idiosyncratic drug-induced liver injury in these patients. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Hepatic FNDC5 is a potential local protective factor against Non-Alcoholic Fatty Liver.
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Canivet, Clémence M., Bonnafous, Stéphanie, Rousseau, Déborah, Leclere, Pierre S., Lacas-Gervais, Sandra, Patouraux, Stéphanie, Sans, Arnaud, Luci, Carmelo, Bailly-Maitre, Béatrice, Iannelli, Antonio, Tran, Albert, Anty, Rodolphe, and Gual, Philippe
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FATTY liver , *LIVER cells , *CARBOHYDRATE metabolism , *OLEIC acid , *LIPID metabolism , *FIBRONECTINS - Abstract
The proteolytic cleavage of Fibronectin type III domain-containing 5 (FNDC5) generates soluble irisin. Initially described as being mainly produced in muscle during physical exercise, irisin mediates adipose tissue thermogenesis and also regulates carbohydrate and lipid metabolism. The aim of this study was to evaluate the hepatic expression of FNDC5 and its role in hepatocytes in Non-Alcoholic Fatty Liver (NAFL). Here we report that hepatic expression of FNDC5 increased with hepatic steatosis and liver injury without impacting the systemic level of irisin in mouse models of NAFLD (HFD and MCDD) and in obese patients. The increased Fndc5 expression in fatty liver resulted from its upregulation in hepatocytes and non-parenchymal cells in mice. The local production of Fndc5 in hepatocytes was influenced by genotoxic stress and p53-dependent pathways. The down-regulation of FNDC5 in human HepG2 cells and in primary mouse hepatocytes increased the expression of PEPCK , a key enzyme involved in gluconeogenesis associated with a decrease in the expression of master genes involved in the VLDL synthesis (CIDEB and APOB). These alterations in FNDC5 -silenced cells resulted to increased steatosis and insulin resistance in response to oleic acid and N -acetyl glucosamine, respectively. The downregulation of Fndc5 also sensitized primary hepatocytes to apoptosis in response to TNFα, which has been associated with decreased hepatoprotective autophagic flux. In conclusion, our human and experimental data strongly suggest that the hepatic expression of FNDC5 increased with hepatic steatosis and its upregulation in hepatocytes could dampen the development of NAFLD by negatively regulating steatogenesis and hepatocyte death. • Hepatic FNDC5 is upregulated in NAFLD without impacting systemic levels of irisin in mouse and human. • Hepatocytes and non-parenchymal cells contribute to increased FNDC5 expression in fatty livers. • Hepatic genotoxic stress and p53 pathway activation could be involved in local upregulation of FNDC5. • FNDC5 in hepatocytes limits steatosis and cytokine-mediated apoptosis. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Dynamic personalized prediction of the individual liver‐related risk after sustained viral response in HCV patients.
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Moreau, Clémence, Roux, Marine, Riou, Jérémie, Canivet, Clémence M., Audureau, Etienne, Lusivika‐Nzinga, Clovis, Nahon, Pierre, Carrat, Fabrice, Boursier, Jérôme, Nahon, P., Layese, R., Audureau, E., Bedossa, P., Bonjour, M., Bourcier, V., Dharancy, S., Durand‐Zaleski, I., Fontaine, H., Guyader, D., and Laurent, A.
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HEPATITIS C virus , *LATENT class analysis (Statistics) , *CHRONIC hepatitis C , *INDIVIDUALIZED medicine , *HEPATOCELLULAR carcinoma - Abstract
Sustained viral response (SVR) significantly improves the prognosis in patients with hepatitis C virus (HCV) chronic infection but does not totally alleviate the risk of liver‐related complications (LRC). We aimed to evaluate whether the dynamics of multiple measurements of simple parameters after SVR enable the development of a personalized prediction of prognosis in HCV patients. HCV mono‐infected patients who experienced SVR in two prospective cohorts (ANRS CO12 CirVir cohort: derivation set; ANRS CO22 HEPATHER cohort: validation set) were included. The study outcome was LRC, a composite criterion including decompensation of cirrhosis and/or hepatocellular carcinoma. Joint latent class modelling accounting for both biomarker trajectory and event occurrence during follow‐up was developed in the derivation set to compute individual dynamic predictions, with further evaluation in the validation set. In the derivation set (n = 695; 50 LRC during the median 3.8 [1.6–7.5] years follow‐up), FIB4 was identified as a biomarker associated with LRC occurrence after SVR. Joint modelling used sex and the dynamics of FIB4 and diabetes status to develop a personalized prediction of LRC. In the validation set (n = 7064; 273 LRC during the median 3.6 [2.5–4.9] years follow‐up), individual dynamic predictions from the model accurately stratified the risk of LRC. Time‐dependent Brier Score showed good calibration that improved with the accumulation of visits, justifying our modelling approach considering both baseline and follow‐up measurements. Dynamic modelling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients. [ABSTRACT FROM AUTHOR]
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- 2023
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9. OS-053 Screening candidates for therapeutic trials in MASH: choose the right non-invasive test for the diagnostic target considered.
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Boursier, Jerome, Vonghia, Luisa, Costentin, Charlotte, Fichez, Jeanne, Moreau, Clemence, Roux, Marine, Canivet, Clémence M, de Lédinghen, Victor, Francque, Sven, and Zheng, Ming-Hua
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- 2024
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10. Systematic screening for advanced liver fibrosis in patients with coronary artery disease: The CORONASH study.
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Thévenot, Thierry, Vendeville, Sophie, Weil, Delphine, Akkouche, Linda, Calame, Paul, Canivet, Clémence M., Vanlemmens, Claire, Richou, Carine, Cervoni, Jean-Paul, Seronde, Marie-France, Di Martino, Vincent, and Boursier, Jérôme
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HEPATIC fibrosis , *CORONARY artery disease , *NON-alcoholic fatty liver disease , *MEDICAL screening , *DISEASE risk factors - Abstract
Although coronary artery disease (CAD) and advanced liver fibrosis (AdLF) are commonly associated in patients with non-alcoholic fatty liver disease (NAFLD), the prevalence of AdLF and the diagnostic performance of non-invasive fibrosis tests (NITs) in CAD patients remains unknown. We aimed to prospectively screen for AdLF in patients with documented CAD using NITs and Fibroscan. High and intermediate zones of NITs were combined to define AdLF. AdLF was suspected whenever APRI ≥ 0.5, Forns index ≥ 4.2, NAFLD fibrosis score (NFS) ≥ -1.455/0.12 for age ≥ 65 yrs), Fib4 (≥ 1.30/2.0 for age ≥ 65 yrs) and eLIFT≥ 8. A presumed AdLF assessed by Fibroscan ≥ 8 kPa was the primary outcome measure. Results were given on the basis of intent-to-diagnose liver stiffness ≥ 8 kPa. Among 189 patients (age 60±7years), 10 (5.3%) had a Fibroscan ≥ 8 kPa, of whom 5 underwent liver biopsy (F3/F4: n = 3; no fibrosis: n = 2). AdLF was suspected in 31% of cases using eLIFT (specificity, Sp 70%), 85% with Forns (Sp 16%), 38% with NFS (Sp 63%), 25% with Fib4 (Sp 74%), and 10% with APRI (Sp 91%). In 149 patients "at-risk" of NAFLD (i.e., elevated ALT or diabetes or hypertriglyceridemia or BMI ≥25 kg/m2), AdLF ranged between 10% (APRI) to 84% (Forns). In this subgroup, the most efficient NITs to predict Fibroscan ≥ 8 kPa were eLIFT (Se 60%, Sp 70%) and NFS (Se 70%, Sp 60%). Finally, in CAD patients with risk factors for NAFLD, NFS or the more user-friendly eLIFT are the most attractive first-line biochemical NITs to discriminate good candidates for Fibroscan. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Non-invasive tests accurately stratify patients with NAFLD based on their risk of liver-related events.
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Boursier, Jerome, Hagström, Hannes, Ekstedt, Mattias, Moreau, Clemence, Bonacci, Martin, Cure, Sandrine, Ampuero, Javier, Nasr, Patrik, Tallab, Lilian, Canivet, Clémence M., Kechagias, Stergios, Sánchez, Yolanda, Dincuff, Eloise, Lucena, Ana, Roux, Marine, Riou, Jeremie, Trylesinski, Aldo, and Romero-Gomez, Manuel
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HEPATIC fibrosis , *NON-alcoholic fatty liver disease , *LIVER biopsy - Abstract
Previous studies on the prognostic significance of non-invasive liver fibrosis tests in non-alcoholic fatty liver disease (NAFLD) lack direct comparison to liver biopsy. We aimed to evaluate the prognostic accuracy of fibrosis-4 (FIB4) and vibration-controlled transient elastography (VCTE), compared to liver biopsy, for the prediction of liver-related events (LREs) in NAFLD. A total of 1,057 patients with NAFLD and baseline FIB4 and VCTE were included in a multicenter cohort. Of these patients, 594 also had a baseline liver biopsy. The main study outcome during follow-up was occurrence of LREs, a composite endpoint combining cirrhosis complications and/or hepatocellular carcinoma. Discriminative ability was evaluated using Harrell's C-index. FIB4 and VCTE showed good accuracy for the prediction of LREs, with Harrell's C-indexes >0.80 (0.817 [0.768-0.866] vs. 0.878 [0.835-0.921], respectively, p = 0.059). In the biopsy subgroup, Harrell's C-indexes of histological fibrosis staging and VCTE were not significantly different (0.932 [0.910-0.955] vs. 0.881 [0.832-0.931], respectively, p = 0.164), while both significantly outperformed FIB4 for the prediction of LREs. FIB4 and VCTE were independent predictors of LREs in the whole study cohort. The stepwise FIB4-VCTE algorithm accurately stratified the risk of LREs: compared to patients with "FIB4 <1.30", those with "FIB4 ≥1.30 then VCTE <8.0 kPa" had similar risk of LREs (adjusted hazard ratio [aHR] 1.3; 95% CI 0.3–6.8), whereas the risk of LREs significantly increased in patients with "FIB4 ≥1.30 then VCTE 8.0-12.0 kPa" (aHR 3.8; 95% CI 1.3–10.9), and even more for those with "FIB4 ≥1.30 then VCTE >12.0 kPa" (aHR 12.4; 95% CI 5.1–30.2). VCTE and FIB4 accurately stratify patients with NAFLD based on their risk of LREs. These non-invasive tests are alternatives to liver biopsy for the identification of patients in need of specialized management. The amount of fibrosis in the liver is closely associated with the risk of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Liver biopsy currently remains the reference standard for the evaluation of fibrosis, but its application is limited by its invasiveness. Therefore, we evaluated the ability of non-invasive liver fibrosis tests to predict liver-related complications in NAFLD. Our results show that the blood test FIB4 and transient elastography stratify the risk of liver-related complications in NAFLD, and that transient elastography has similar prognostic accuracy as liver biopsy. These results support the use of non-invasive liver fibrosis tests instead of liver biopsy for the management of patients with NAFLD. [Display omitted] • At their published cut-offs, FIB4 and VCTE stratify patients with NAFLD into subgroups with significantly different prognoses. • Compared to liver biopsy in NAFLD, VCTE has similar accuracy for the prediction of liver-related events. • With regards to clinical events, the FIB4-VCTE stepwise algorithm accurately discriminates at-risk patients with NAFLD. • This algorithm should be used in the referral pathway to a liver specialist. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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12. Acute hepatitis B in pregnancy with surprisingly rapid clearance of serum HBs antigen associated with a favourable outcome.
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Roger, Steven, Fontana, Julien, Ducancelle, Alexandra, Le Guillou-Guillemette, Hélène, Canivet, Clémence M, and Lefeuvre, Caroline
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HEPATITIS B , *CHRONIC hepatitis B , *HEPATITIS B virus , *DISEASE risk factors , *PREGNANT women , *PREGNANCY - Abstract
• HBsAg seroclearance may vary according to the precore/core mutations. • HBsAg seroclearance may vary according to the hepatitis B virus (HBV) genotype. • Pregnancy might be a risk factor for chronicity following acute HBV infection. • Antiviral drugs in cases of acute hepatitis B (AHB) in pregnancy may prevent progression to chronicity. Acute hepatitis B (AHB) is usually asymptomatic, but it can progress to chronic hepatitis B (HB) defined by HB surface antigen (HBsAg) persisting beyond 6 months. Nevertheless, the delay of HBsAg seroclearance is not well-defined. During pregnancy, the immune system of the pregnant women is altered and delayed HBsAg loss can be observed, leading to chronic infection. Here, we present an uncommon case of AHB in a pregnant woman in whom rapid HBsAg seroclearance (52 days after AHB) was associated with a favourable outcome (no injury to liver). This patient received tenofovir disoproxil fumarate promptly after diagnosis. The case raises questions about the use of antiviral treatment in AHB. This is generally not recommended in AHB, but it would be potentially useful in pregnant women to reduce the risk of chronic HB infection and could also prevent the transmission of the maternal precore mutation, thus reducing the significant risk of fulminant hepatitis in the infant. This case also highlights the impact of the hepatitis B virus (HBV) genotype and precore/core mutations on the clinical course of the disease. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease.
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David, Norma, Antignac, Jean-Philippe, Roux, Marine, Marchand, Philippe, Michalak, Sophie, Oberti, Fréderic, Fouchard, Isabelle, Lannes, Adrien, Blanchet, Odile, Cales, Paul, Blanc, Etienne B., Boursier, Jérôme, and Canivet, Clémence M.
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NON-alcoholic fatty liver disease , *FLUOROALKYL compounds , *LIQUID chromatography-mass spectrometry , *HIGH performance liquid chromatography - Abstract
[Display omitted] • 9/17 PFAS were detected in more than 50% of the patients. • PFDA, PFNA, PFOA, PFOS and PFHxS were detected in all patients. • Higher concentrations of PHFpA were associated with liver steatosis. • PFHpA could disturb NAFLD natural history being involved in liver steatosis. Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and the determinants driving its severity remain to be elucidated. Perfluoroalkyl substances (PFAS) are synthetic chemical compounds. They are used in commonplace products and persistent in water, soil and the human body. In vitro and animal studies suggest a pathogenic role for PFAS in metabolic diseases such as NAFLD. We aimed to evaluate the association between NAFLD severity and serum PFAS concentrations in humans. One hundred biopsy-proven NAFLD patients were included with a well-balanced distribution between the different stages of severity: 25 patients with simple steatosis, 25 with early non-alcoholic steatohepatitis (NASH and F0–F1 fibrosis), 33 with fibrotic NASH (NASH and F2–F3 fibrosis), and 17 with cirrhotic NASH (NASH and F4 fibrosis). Liver histological features were evaluated according to the NASH Clinical Research Network classification. Seventeen PFAS were measured by high-performance liquid chromatography coupled with tandem mass spectrometry on serum samples stored at −80 °C. The median age was 60 years, 61 % of patients were male, 46 % had diabetes and the median body mass index (BMI) was 32 kg/m2. Long-chain PFAS were associated with steatosis grade (p = 0.03). Among the nine PFAS detected in > 50 % of the patients, Perfluoro-n-heptanoic acid (PFHpA) showed significantly higher concentrations in grade 3 steatosis versus grade 1 (p = 0.02). Perfluoro-n-dodecanoic acid (PFDoA) concentrations were higher in patients with significant fibrosis (p = 0.04) and PFHpA in patients with advanced fibrosis (p = 0.02). The association between PFHpA and steatosis grade remained significant in multivariate analysis adjusted for age, gender, BMI, diabetes presence and dyslipidemia (p = 0.004). Our study showed a significant association between PFHpA and liver steatosis in NAFLD. According to data available in the literature, PFHpA could be implicated in liver steatosis through β-oxidation and biosynthesis of fatty acids. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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14. CD44 is a key player in non-alcoholic steatohepatitis.
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Patouraux, Stéphanie, Rousseau, Déborah, Bonnafous, Stéphanie, Lebeaupin, Cynthia, Luci, Carmelo, Canivet, Clémence M., Schneck, Anne-Sophie, Bertola, Adeline, Saint-Paul, Marie-Christine, Iannelli, Antonio, Gugenheim, Jean, Anty, Rodolphe, Tran, Albert, Bailly-Maitre, Béatrice, and Gual, Philippe
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FATTY liver , *FAT , *INFLAMMATION , *LEUCOCYTES , *NEUTROPHILS , *CHEMOKINES - Abstract
Background & Aims Cluster of differentiation (CD)44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. We aimed to evaluated the contribution of CD44 to non-alcoholic steatohepatitis (NASH) development and liver injury in mouse models and in patients at various stages of non-alcoholic fatty liver disease (NAFLD) progression. Methods The role of CD44 was evaluated in CD44 −/− mice and after injections of an αCD44 antibody in wild-type mice challenged with a methionine- and choline-deficient diet (MCDD). In obese patients, hepatic CD44 (n = 30 and 5 NASH patients with a second liver biopsy after bariatric surgery) and serum sCD44 (n = 64) were evaluated. Results Liver inflammation (including inflammatory foci number, macrophage and neutrophil infiltration and CCL2/CCR2 levels), liver injury and fibrosis strongly decreased in CD44 −/− mice compared to wild-type mice on MCDD. CD44 deficiency enhanced the M2 polarization and strongly decreased the activation of macrophages by lipopolysaccharide (LPS), hepatocyte damage-associated molecular patterns (DAMPs) and saturated fatty acids. Neutralization of CD44 in mice with steatohepatitis strongly decreased the macrophage infiltration and chemokine ligand (CCL)2 expression with a partial correction of liver inflammation and injury. In obese patients, hepatic CD44 was strongly upregulated in NASH patients ( p = 0.0008) and correlated with NAFLD activity score (NAS) ( p = 0.001), ballooning ( p = 0.003), alanine transaminase ( p = 0.005) and hepatic CCL2 ( p <0.001) and macrophage marker CD68 ( p <0.001) expression. Correction of NASH was associated with a strong decrease in liver CD44 + cells. Finally, the soluble form of CD44 increased with severe steatosis ( p = 0.0005) and NASH ( p = 0.007). Conclusion Human and experimental data suggest that CD44 is a marker and key player of hepatic inflammation and its targeting partially corrects NASH. Lay summary Human and experimental data suggest that CD44, a cellular protein mainly expressed in immune cells, is a marker and key player of non-alcoholic steatohepatitis (NASH). Indeed, CD44 enhances the non-alcoholic fatty liver (NAFL) (hepatic steatosis) to NASH progression by regulating hepatic macrophage polarization (pro-inflammatory phenotype) and infiltration (macrophage motility and the MCP1/CCL2/CCR2 system). Targeting CD44 partially corrects NASH, making it a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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