509 results on '"Jean-François Dufour"'
Search Results
2. Transcriptomics-driven metabolic pathway analysis reveals similar alterations in lipid metabolism in mouse MASH model and human
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Sofia Tsouka, Pavitra Kumar, Patcharamon Seubnooch, Katrin Freiburghaus, Marie St-Pierre, Jean-François Dufour, and Mojgan Masoodi
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Medicine - Abstract
Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease worldwide, and can rapidly progress to metabolic dysfunction-associated steatohepatitis (MASH). Accurate preclinical models and methodologies are needed to understand underlying metabolic mechanisms and develop treatment strategies. Through meta-analysis of currently proposed mouse models, we hypothesized that a diet- and chemical-induced MASH model closely resembles the observed lipid metabolism alterations in humans. Methods We developed transcriptomics-driven metabolic pathway analysis (TDMPA), a method to aid in the evaluation of metabolic resemblance. TDMPA uses genome-scale metabolic models to calculate enzymatic reaction perturbations from gene expression data. We performed TDMPA to score and compare metabolic pathway alterations in MASH mouse models to human MASH signatures. We used an already-established WD+CCl4-induced MASH model and performed functional assays and lipidomics to confirm TDMPA findings. Results Both human MASH and mouse models exhibit numerous altered metabolic pathways, including triglyceride biosynthesis, fatty acid beta-oxidation, bile acid biosynthesis, cholesterol metabolism, and oxidative phosphorylation. We confirm a significant reduction in mitochondrial functions and bioenergetics, as well as in acylcarnitines for the mouse model. We identify a wide range of lipid species within the most perturbed pathways predicted by TDMPA. Triglycerides, phospholipids, and bile acids are increased significantly in mouse MASH liver, confirming our initial observations. Conclusions We introduce TDMPA, a methodology for evaluating metabolic pathway alterations in metabolic disorders. By comparing metabolic signatures that typify human MASH, we show a good metabolic resemblance of the WD+CCl4 mouse model. Our presented approach provides a valuable tool for defining metabolic space to aid experimental design for assessing metabolism.
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- 2024
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3. Current Challenges in Treating Unresectable Hepatocellular Carcinoma
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Jean-François Dufour
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Medicine - Abstract
For a decade, sorafenib was the only available treatment option for patients with unresectable hepatocellular carcinoma (HCC). The surge in systemic therapies for the treatment of HCC patients over the past five years resulted in significantly prolonged survival and improved quality of life. However, due to the lack of predictive biomarkers of treatment response, it has also introduced challenges in clinical decision-making. This article provides an overview of the complexities in the treatment of patients with HCC. PEER REVIEWED ARTICLE Peer reviewers: Dr Thibaud Kössler (Geneva University Hospitals, Geneva, Switzerland) Prof. Jörg Trojan (University Hospital Frankfurt, Frankfurt, Germany) Submitted: November 14, 2023 CEST; Accepted: December 07, 2023 CEST
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- 2023
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4. Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study
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Huai Zhang, Rafael S. Rios, Jerome Boursier, Rodolphe Anty, Wah-Kheong Chan, Jacob George, Yusuf Yilmaz, Vincent Wai-Sun Wong, Jiangao Fan, Jean-François Dufour, George Papatheodoridis, Li Chen, Jörn M. Schattenberg, Junping Shi, Liang Xu, Grace Lai-Hung Wong, Naomi F. Lange, Margarita Papatheodoridi, Yuqiang Mi, Yujie Zhou, Christopher D. Byrne, Giovanni Targher, Gong Feng, Minghua Zheng, and Yuanyuan Ji
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Medicine - Abstract
Abstract. Background:. Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. Methods:. Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). Results:. A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69–1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension (P
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- 2023
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5. Should we undertake surveillance for HCC in patients with MAFLD?
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Blanca Norero and Jean-François Dufour
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Over the last decade, metabolic-associated fatty liver disease (MAFLD) has become an important public health issue worldwide. In many countries, MAFLD has become the most common cause of chronic liver disease. On the contrary, hepatocellular carcinoma (HCC) mortality is rising. Liver tumors have become the third cause of cancer mortality worldwide. HCC is the most frequent liver tumor. While the burden of HCC related to viral hepatitis is declining, the prevalence of MAFLD-related HCC is rising rapidly. Classical screening criteria for HCC consider cirrhotic, advanced fibrosis, and viral hepatitis patients. Metabolic syndrome with liver involvement or MAFLD is associated with a higher risk of HCC development, even in the absence of cirrhosis. The question about the cost effectiveness of surveillance for HCC in MAFLD is yet not fully answered. There are no guidelines that address the question of when to start or how to define the population who can benefit of surveillance for HCC in MAFLD patients. This review aims to revise the evidence of HCC development in MAFLD. It hopes to be a step closer to defining screening criteria for HCC in MAFLD.
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- 2023
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6. Vasculitis and familial Mediterranean fever: Description of 22 French adults from the juvenile inflammatory rheumatism cohort
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Salam Abbara, Jean-Benoit Monfort, Léa Savey, Philippe Moguelet, David Saadoun, Claude Bachmeyer, Olivier Fain, Benjamin Terrier, Zahir Amoura, Alexis Mathian, Laurent Gilardin, David Buob, Chantal Job-Deslandre, Jean-François Dufour, Rebecca Sberro-Soussan, Gilles Grateau, and Sophie Georgin-Lavialle
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vasculitis ,familial Mediterranean fever ,polyarteritis nodosa ,IgA vasculitis ,pyrin ,anti-neutrophil cytoplasmic antibody-associated vasculitis ,Medicine (General) ,R5-920 - Abstract
ObjectiveThe frequency of vasculitis may be increased in patients with Familial Mediterranean Fever (FMF), according to several studies. Our aim was to assess the characteristics of French adult patients with both diseases.MethodsPatients with vasculitis were selected from patients followed for FMF in the French JIR-cohort.ResultsTwenty-two patients were included [polyarteritis nodosa (PAN) n = 10, IgA vasculitis n = 8, unclassified vasculitis n = 2, granulomatosis with polyangiitis n = 1, and microscopic polyangiitis n = 1]. Pathogenic mutations in exon 10 were found in all 21 patients (96%) for which MEFV testing results were available, and 18 (82%) had two pathogenic mutations. Histology showed vasculitis in 59% of patients. Most patients with FMF-associated PAN were HBV-negative and had an inactive FMF before PAN onset, and 40% had a peri-renal or central nervous system bleeding. Most patients with FMF-associated IgA vasculitis had an active FMF before vasculitis onset, and 25% had digestive bleeding. Both patients with unclassified vasculitis had ischemic and/or hemorrhagic complications.ConclusionThis study confirms the predominance of PAN and IgA vasculitis in patients with FMF and the high frequency of bleeding in FMF-associated PAN. FMF should be considered in case of persistent symptoms and/or inflammatory syndrome despite vasculitis treatment in Mediterranean patients.
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- 2022
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7. Effects of Home Care on patients with hepatocellular carcinoma treated with sorafenib
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Monika Moser, Iuliana‐Pompilia Radu, and Jean‐François Dufour
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liver cancer ,oncology ,quality of life ,sorafenib ,treatment ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and Aim Treatment with sorafenib causes diverse side effects, which limits adherence. This work assesses whether Home Care, a psychosocial nursing intervention, prolongs the duration of treatment in patients with advanced hepatocellular carcinoma (HCC) and if it influences health‐related quality of life (HRQL). Methods and Results This is a cohort study using data from patients receiving sorafenib in the prospective Bern HCC Cohort at the University Hospital. Duration of treatment, overall survival, and HRQL using the Functional Assessment of Cancer Therapy‐Hepatobiliary questionnaire were compared in the two groups. A total of 173 patients were eligible for the analysis. Among them, 141 were in the Home Care program, and 32 were not. Patients with Home Care had a significantly longer duration of treatment (265 days vs 152 days, P = 0.003) and a better functional well‐being (17.7 vs 12.5, P = 0.015). Conclusion Psychosocial interventions such as Home Care are a valid method in improving adherence to sorafenib and can therefore be recommended.
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- 2021
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8. Endoplasmic Reticulum and Mitochondria Contacts Correlate with the Presence and Severity of NASH in Humans
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Chaonan Jin, Eric Felli, Naomi Franziska Lange, Annalisa Berzigotti, Jordi Gracia-Sancho, and Jean-François Dufour
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mitochondria ,endoplasmic reticulum ,NASH ,NAFLD ,MAFLD ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The interaction between the mitochondria and the endoplasmic reticulum (ER) is essential for hepatocyte function. An increase in ER–mitochondria contacts (ERMCs) is associated with various metabolic diseases. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes, and its progressive form non-alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. However, the role of ERMCs in the progression of NAFL to NASH is still unclear. We assessed whether ERMCs could correlate with NAFLD severity. We used a proximity ligation assay to measure the abundance of ERMCs in liver biopsies from patients with biopsy-proven NAFLD (n = 48) and correlated the results with histological and metabolic syndrome (MetS) features. NAFLD patients were included according to inclusion and exclusion criteria, and then assigned to NAFL (n = 9) and NASH (n = 39) groups. ERMCs density could discriminate NASH from NAFL (sensitivity 61.5%, specificity 100%). ERMCs abundance correlated with hepatocellular ballooning. Moreover, the density of ERMCs increased with an increase in the number of MetS features. In conclusion, ERMCs increased from NAFL to NASH, in parallel with the number of MetS features, supporting a role for this interaction in the pathophysiology of NASH.
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- 2022
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9. The global epidemiology of nonalcoholic steatohepatitis (NASH) and associated risk factors–A targeted literature review
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Jean-François Dufour, Roger Scherer, Maria-Magdalena Balp, Sarah Jane McKenna, Nico Janssens, Patricia Lopez, and Marcos Pedrosa
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NASH ,NAFLD ,Prevalence ,Disease progression ,Risk factors ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background: There is a wide variation across studies in the reported prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). A targeted literature review was conducted to understand the prevalence of NALFD and NASH in the general population and specific sub-populations as well as identify risk factors associated with NASH. Methods: Embase and Medline databases (2003–July 2018, English language) and relevant conferences were searched to identify observational studies and meta-analysis reporting outcomes of interest. Small cohort studies (
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- 2021
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10. PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients
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Naomi F. Lange, Vanessa Graf, Cyrielle Caussy, and Jean-François Dufour
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non-alcoholic fatty liver disease (NAFLD) ,non-alcoholic steatohepatitis (NASH) ,type 2 diabetes mellitus ,peroxisome proliferator-activated receptors (PPAR) ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Peroxisome proliferator-activated receptors (PPAR), ligand-activated transcription factors of the nuclear hormone receptor superfamily, have been identified as key metabolic regulators in the liver, skeletal muscle, and adipose tissue, among others. As a leading cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) cause a significant burden worldwide and therapeutic strategies are needed. This review provides an overview of the evidence on PPAR-targeted treatment of NAFLD and NASH in individuals with type 2 diabetes mellitus. We considered current evidence from clinical trials and observational studies as well as the impact of treatment on comorbid metabolic conditions such as obesity, dyslipidemia, and cardiovascular disease. Future areas of research, such as possible sexually dimorphic effects of PPAR-targeted therapies, are briefly reviewed.
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- 2022
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11. Intestinal microbiota drives cholestasis-induced specific hepatic gene expression patterns
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Oriol Juanola, Mohsin Hassan, Pavitra Kumar, Bahtiyar Yilmaz, Irene Keller, Cédric Simillion, Cornelius Engelmann, Frank Tacke, Jean-François Dufour, Andrea De Gottardi, and Sheida Moghadamrad
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intestinal microbiota ,acute cholestasis ,bile acids ,gene expression ,germ-free mice ,metabolism ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Intestinal microbiota regulates multiple host metabolic and immunological processes. Consequently, any difference in its qualitative and quantitative composition is susceptible to exert significant effects, in particular along the gut-liver axis. Indeed, recent findings suggest that such changes modulate the severity and the evolution of a wide spectrum of hepatobiliary disorders. However, the mechanisms linking intestinal microbiota and the pathogenesis of liver disease remain largely unknown. In this work, we investigated how a distinct composition of the intestinal microbiota, in comparison with germ-free conditions, may lead to different outcomes in an experimental model of acute cholestasis. Acute cholestasis was induced in germ-free (GF) and altered Schaedler’s flora (ASF) colonized mice by common bile duct ligation (BDL). Studies were performed 5 days after BDL and hepatic histology, gene expression, inflammation, lipids metabolism, and mitochondrial functioning were evaluated in normal and cholestatic mice. Differences in plasma concentration of bile acids (BA) were evaluated by UHPLC-HRMS. The absence of intestinal microbiota was associated with significant aggravation of hepatic bile infarcts after BDL. At baseline, we found the absence of gut microbiota induced altered expression of genes involved in the metabolism of fatty and amino acids. In contrast, acute cholestasis induced altered expression of genes associated with extracellular matrix, cell cycle, autophagy, activation of MAPK, inflammation, metabolism of lipids, and mitochondrial functioning pathways. Ductular reactions, cell proliferation, deposition of collagen 1 and autophagy were increased in the presence of microbiota after BDL whereas GF mice were more susceptible to hepatic inflammation as evidenced by increased gene expression levels of osteopontin, interleukin (IL)-1β and activation of the ERK/MAPK pathway as compared to ASF colonized mice. Additonally, we found that the presence of microbiota provided partial protection to the mitochondrial functioning and impairment in the fatty acid metabolism after BDL. The concentration of the majority of BA markedly increased after BDL in both groups without remarkable differences according to the hygiene status of the mice. In conclusion, acute cholestasis induced more severe liver injury in GF mice compared to mice with limited intestinal bacterial colonization. This protective effect was associated with different hepatic gene expression profiles mostly related to tissue repair, metabolic and immune functions. Our findings suggest that microbial-induced differences may impact the course of cholestasis and modulate liver injury, offering a background for novel therapies based on the modulation of the intestinal microbiota.
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- 2021
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12. Antitumour necrosis factor-α agents and development of new-onset cirrhosis or non-alcoholic fatty liver disease: a retrospective cohort
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Susan Hutfless, Ruben Hernaez, Kuo-Tung Tang, Jean-François Dufour, and Po-Hung Chen
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
ObjectiveElevated tumour necrosis factor (TNF)-α has been implicated in the progression of liver fibrosis and pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aim to investigate the impact of anti-TNF-α agents on the development of cirrhosis and NAFLD.DesignThis retrospective cohort study used a US claims database between 1 January 2010 and 31 December 2016. We identified adult patients with ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis or rheumatoid arthritis. Anti-TNF-α agents of interest included adalimumab, certolizumab, etanercept, golimumab and infliximab. The primary composite outcome was the development of new-onset cirrhosis, NAFLD or non-alcoholic steatohepatitis (NASH). The secondary outcomes were the development of (1) cirrhosis and (2) NAFLD or NASH. Propensity score for anti-TNF-α agent use was generated by logistic regression. Cox proportional hazard models adjusting for the propensity score were used with regard to time-varying anti-TNF-α agent exposure.ResultsThis study included 226 555 incident patients with immune-related diseases. During the median 1.5 years follow-up, there was an increased hazard with anti-TNF-α agent use in regard to liver outcomes (composite outcome HR: 1.47, 95% CI 1.27 to 1.70; cirrhosis HR 1.47, 95% CI 0.96 to 2.23; NAFLD or NASH HR 1.53, 95% CI 1.32 to 1.77). The composite outcome hazard was increased for each immune-related disease (HR 1.25–1.90).ConclusionIn the short term, we did not observe a beneficial effect of anti-TNF-α agent use for development of cirrhosis, NAFLD or NASH in patients with immune-related diseases.
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- 2020
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13. Nuclear deformation mediates liver cell mechanosensing in cirrhosis
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Sergi Guixé-Muntet, Martí Ortega-Ribera, Cong Wang, Sonia Selicean, Ion Andreu, Jenny Z. Kechagia, Constantino Fondevila, Pere Roca-Cusachs, Jean-François Dufour, Jaime Bosch, Annalisa Berzigotti, and Jordi Gracia-Sancho
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Chronic liver disease ,Hepatocyte ,HSC ,LSEC ,Stiffness ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Liver stiffness is increased in advanced chronic liver disease (ACLD) and accurately predicts prognosis in this population. Recent data suggest that extracellular matrix stiffness per se may modulate the phenotype of liver cells. We aimed at investigating the effect of matrix stiffness on the phenotype of liver cells of rats with cirrhosis, assessing its influence on their response to antifibrotic strategies and evaluating associated molecular mechanisms. Methods: Hepatocytes, hepatic stellate cells, and liver sinusoidal endothelial cells were isolated from healthy rats or rats with cirrhosis (carbon tetrachloride or thioacetamide), and cultured on polyacrylamide gels with different physiologically relevant stiffness for 72 h. Results: All cell types of rats with cirrhosis cultured at low stiffness showed a significant phenotype amelioration vs. rigid matrix (assessed by quantitative morphology, mRNA expression, protein synthesis, and electron microscopy imaging). Additionally, stiffness modified the antifibrotic effects of liraglutide in stellate cells of rats with cirrhosis. Finally, evaluation of nuclear morphology revealed that high stiffness induced nuclei deformation in all cell types, an observation confirmed in cells from human livers. Disconnecting the nucleus from the cytoskeleton by cytoskeleton disruption or a defective form of nesprin 1 significantly recovered spherical nuclear shape and quiescent phenotype of cells. Conclusions: The environment's stiffness per se modulates the phenotype of healthy rats and liver cells of rats with cirrhosis by altering the nuclear morphology through cytoskeleton-derived mechanical forces. The reversibility of this mechanism suggests that targeting the stiffness-mediated intracellular mechanical tensions may represent a novel therapeutic strategy for ACLD. Lay summary: During cirrhosis, the liver becomes scarred, stiff, and unable to perform its normal functions efficiently. In this study, we demonstrated that cells from diseased (stiff) livers recovered their functionality when placed in a soft environment (as that of a healthy liver). Furthermore, treatments aimed at tricking liver cells into believing they are in a healthy, soft liver improved their function and could potentially contribute to treat cirrhosis.
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- 2020
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14. Prognostic Significance of Controlled Attenuation Parameter in Patients With Compensated Advanced Chronic Liver Disease
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Cristina Margini, Giuseppe Murgia, Guido Stirnimann, Andrea De Gottardi, Nasser Semmo, Stefania Casu, Jaime Bosch, Jean‐François Dufour, and Annalisa Berzigotti
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Obesity and steatosis have been associated with liver disease progression in patients with compensated advanced chronic liver disease (cACLD) (liver stiffness measurement [LSM] ≥ 10 kPa). The controlled attenuation parameter (CAP) estimates steatosis during LSM by transient elastography. We aimed to evaluate whether CAP is associated with the development of clinically relevant events in cACLD. Consecutive patients with cACLD and CAP measurements observed between September 2013 and September 2015 were retrospectively studied. Classical decompensation and severe bacterial infections on follow‐up were recorded. A predefined CAP cut‐off for steatosis was used (220 dB/m; 90% sensitivity). The association among LSM, CAP, and events was assessed by univariate and multivariate Cox regression. Among the 193 patients (viral etiology = 58%; median Child score = 5; LSM = 15.1 kPa; CAP = 255 ± 62 dB/m) who were followed up in median for 18 months, 18 developed clinically relevant events (11 liver decompensation, 7 severe bacterial infections). Patients developing events had higher LSM (median: 30.8 versus 14.3 kPa, P < 0.001) and showed trends for higher CAP (275 ± 46 versus 252 ± 63 dB/m, P = 0.07), lower platelet count (134 ± 74 versus 167 ± 74 G/L, P = 0.07), and worse liver function versus patients remaining compensated. Body mass index was similar in the two groups. All events were more frequent in patients with CAP being greater than or equal to 220 dB/m (12.9% versus 1.6% in CAP < 220; P = 0.013), and 10 of 11 episodes of liver decompensation occurred in patients with CAP being greater than or equal to 220 dB/m. Following multivariate analysis, LSM and CAP greater than or equal to 220 dB/m remained independently associated with clinical events in the whole population and in patients with clinically significant portal hypertension. Conclusion: The CAP being greater than or equal to 220 dB/m is associated with increased risk of clinical decompensation and bacterial infections independent of LSM in patients with cACLD and allows refining the noninvasive risk stratification in this population. (Hepatology Communications 2018; 00:000‐000)
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- 2018
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15. Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing
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Frédégonde About, Stéphanie Bibert, Emmanuelle Jouanguy, Bertrand Nalpas, Lazaro Lorenzo, Vimel Rattina, Mohammed Zarhrate, Sylvain Hanein, Mona Munteanu, Beat Müllhaupt, David Semela, Nasser Semmo, Jean-Laurent Casanova, Ioannis Theodorou, Philippe Sultanik, Thierry Poynard, Stanislas Pol, Pierre-Yves Bochud, Aurélie Cobat, Laurent Abel, The Swiss Hepatitis C Cohort Study Group, The French ANRS HC EP 26 Genoscan Study Group, Francesco Negro, Antoine Hadengue, Laurent Kaiser, Laura Rubbia-Brandt, Darius Moradpour, Cristina Cellerai, Martin Rickenbach, Andreas Cerny, Gladys Martinetti, Jean-François Dufour, Meri Gorgievski, Virginie Masserey Spicher, Markus Heim, Hans Hirsch, Beat Helbling, Stephan Regenass, Raffaele Malinverni, Guenter Dollenmaier, and Gieri Cathomas
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endoglin ,HCV-related liver fibrosis ,exome sequencing ,TGF-beta ,rare-variant association study ,Genetics ,QH426-470 - Abstract
Despite the astonishing progress in treating chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents, liver fibrosis remains a major health concern in HCV infected patients, in particular due to the treatment cost and insufficient HCV screening in many countries. Only a fraction of patients with chronic HCV infection develop liver fibrosis. While there is evidence that host genetic factors are involved in the development of liver fibrosis, the common variants identified so far, in particular by genome-wide association studies, were found to have limited effects. Here, we conducted an exome association study in 88 highly selected HCV-infected patients with and without fibrosis. A strategy focusing on TGF-β pathway genes revealed an enrichment in rare variants of the endoglin gene (ENG) in fibrosis patients. Replication studies in additional cohorts (617 patients) identified one specific ENG variant, Thr5Met, with an overall odds ratio for fibrosis development in carriers of 3.04 (1.39–6.69). Our results suggest that endoglin, a key player in TGF-β signaling, is involved in HCV-related liver fibrogenesis.
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- 2019
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16. Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis
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Marta Correia de Sousa, Nicolas Calo, Cyril Sobolewski, Monika Gjorgjieva, Sophie Clément, Christine Maeder, Dobrochna Dolicka, Margot Fournier, Laurent Vinet, Xavier Montet, Jean-François Dufour, Bostjan Humar, Francesco Negro, Christine Sempoux, and Michelangelo Foti
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microRNA 21 ,HCC ,oncogenes ,tumor suppressors ,inflammation ,fibrosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The microRNA 21 (miR-21) is upregulated in almost all known human cancers and is considered a highly potent oncogene and potential therapeutic target for cancer treatment. In the liver, miR-21 was reported to promote hepatic steatosis and inflammation, but whether miR-21 also drives hepatocarcinogenesis remains poorly investigated in vivo. Here we show using both carcinogen (Diethylnitrosamine, DEN) or genetically (PTEN deficiency)-induced mouse models of hepatocellular carcinoma (HCC), total or hepatocyte-specific genetic deletion of this microRNA fosters HCC development—contrasting the expected oncogenic role of miR-21. Gene and protein expression analyses of mouse liver tissues further indicate that total or hepatocyte-specific miR-21 deficiency is associated with an increased expression of oncogenes such as Cdc25a, subtle deregulations of the MAPK, HiPPO, and STAT3 signaling pathways, as well as alterations of the inflammatory/immune anti-tumoral responses in the liver. Together, our data show that miR-21 deficiency promotes a pro-tumoral microenvironment, which over time fosters HCC development via pleiotropic and complex mechanisms. These results question the current dogma of miR-21 being a potent oncomiR in the liver and call for cautiousness when considering miR-21 inhibition for therapeutic purposes in HCC.
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- 2021
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17. COVID-19 in Liver Transplant Recipients: A Systematic Review
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Chiara Becchetti, Sarah Gabriela Gschwend, Jean-François Dufour, and Vanessa Banz
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solid organ transplantation ,liver injury ,immunosuppressant ,SARS-CoV-2 ,humoral response ,vaccination ,Medicine - Abstract
Liver transplant (LT) recipients are considered a vulnerable population amidst the COVID-19 pandemic. To date, available data have been heterogeneous and scarce. Therefore, we conducted a systematic literature review identifying English-language articles published in PubMed between November 2019 and 30 May 2021. We aimed to explore three areas: (1) outcome and clinical course; (2) immunological response after COVID-19 in LT recipients; and (3) vaccination response. After systematic selection, 35, 4, and 5 articles, respectively, were considered suitable for each area of analysis. Despite the heterogeneity of the reports included in this study, we found that gastrointestinal symptoms were common in LT recipients. The outcome of the LT population was not per se worse compared to the general population, although careful management of immunosuppressive therapy is required. While a complete therapy discontinuation is not encouraged, caution needs to be taken with use of mycophenolate mofetil (MMF), favoring tacrolimus (TAC) use. Although data conflicted about acquired immunity after SARS-CoV-2 infection, vaccine immunogenicity appeared to be low, suggesting that the level of surveillance should be kept high in this population.
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- 2021
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18. Intricate interpretation of etiology-specific outcome comparison in patients with hepatocellular carcinoma
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Hwi Young Kim and Jean-François Dufour
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2020
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19. A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?
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Nardeen Eldafashi, Rebecca Darlay, Ruchi Shukla, Misti Vanette McCain, Robyn Watson, Yang Lin Liu, Nikki McStraw, Moustafa Fathy, Michael Atef Fawzy, Marco Y. W. Zaki, Ann K. Daly, João P. Maurício, Alastair D. Burt, Beate Haugk, Heather J. Cordell, Cristiana Bianco, Jean-François Dufour, Luca Valenti, Quentin M. Anstee, and Helen L. Reeves
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primary liver cancer ,hepatocellular carcinoma ,metabolic syndrome ,genetic predisposition ,single-nucleotide polymorphism ,PDCD1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409; TM6SF2 rs58542926). Here, we have considered single-nucleotide polymorphisms (SNPs) in candidate immunoregulatory genes (MICA rs2596542; CD44 rs187115; PDCD1 rs7421861 and rs10204525), in 594 patients with NAFLD and 391 with NAFLD-HCC, from three European centres. Associations between age, body mass index, diabetes, cirrhosis and SNPs with HCC development were explored. PNPLA3 and TM6SF2 SNPs were associated with both progression to cirrhosis and NAFLD-HCC development, while PDCD1 SNPs were specifically associated with NAFLD-HCC risk, regardless of cirrhosis. PDCD1 rs7421861 was independently associated with NAFLD-HCC development, while PDCD1 rs10204525 acquired significance after adjusting for other risks, being most notable in the smaller numbers of women with NAFLD-HCC. The study highlights the potential impact of inter individual variation in immune tolerance induction in patients with NAFLD, both in the presence and absence of cirrhosis.
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- 2021
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20. Clinical and Genetic Tumor Characteristics of Responding and Non-Responding Patients to PD-1 Inhibition in Hepatocellular Carcinoma
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Stephan Spahn, Daniel Roessler, Radu Pompilia, Gisela Gabernet, Beryl Primrose Gladstone, Marius Horger, Saskia Biskup, Magdalena Feldhahn, Sven Nahnsen, Franz J. Hilke, Bernhard Scheiner, Jean-François Dufour, Enrico N. De Toni, Matthias Pinter, Nisar P. Malek, and Michael Bitzer
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hepatocellular carcinoma ,immunotherapy ,biomarkers ,microbiome ,tumor mutational burden ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Immune checkpoint inhibitors (ICIs) belong to the therapeutic armamentarium in advanced hepatocellular carcinoma (HCC). However, only a minority of patients benefit from immunotherapy. Therefore, we aimed to identify indicators of therapy response. This multicenter analysis included 99 HCC patients. Progression-free (PFS) and overall survival (OS) were studied by Kaplan-Meier analyses for clinical parameters using weighted log-rank testing. Next-generation sequencing (NGS) was performed in a subset of 15 patients. The objective response (OR) rate was 19% median OS (mOS)16.7 months. Forty-one percent reached a PFS > 6 months; these patients had a significantly longer mOS (32.0 vs. 8.5 months). Child-Pugh (CP) A and B patients showed a mOS of 22.1 and 12.1 months, respectively. Ten of thirty CP-B patients reached PFS > 6 months, including 3 patients with an OR. Tumor mutational burden (TMB) could not predict responders. Of note, antibiotic treatment within 30 days around ICI initiation was associated with significantly shorter mOS (8.5 vs. 17.4 months). Taken together, this study shows favorable outcomes for OS with low AFP, OR, and PFS > 6 months. No specific genetic pattern, including TMB, could identify responders. Antibiotics around treatment initiation were associated with worse outcome, suggesting an influence of the host microbiome on therapy success.
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- 2020
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21. Treatment allocation in hepatocellular carcinoma: Assessment of the BCLC algorithm
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Mandy Richani, Philippe Kolly, Marina Knoepfli, Evelyn Herrmann, Martin Zweifel, Hendrik von Tengg-Kobligk, Daniel Candinas, and Jean-François Dufour
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Barcelona Clinic Liver Cancer ,Bern Clinic Liver Cancer ,Performance status ,Specialties of internal medicine ,RC581-951 - Abstract
Background and aims. The Barcelona Clinic Liver Cancer (BCLC) staging system is the algorithm most widely used to manage patients with hepatocellular carcinoma (HCC). We aimed to investigate the extent to which the BCLC recommendations effectively guide clinical practice and assess the reasons for any deviation from the recommendations.Material and methods. The first-line treatments assigned to patients included in the prospective Bern HCC cohort were analyzed.Results. Among 223 patients included in the cohort, 116 were not treated according to the BCLC algorithm. Eighty percent of the patients in BCLC stage 0 (very early HCC) and 60% of the patients in BCLC stage A (early HCC) received recommended curative treatment. Only 29% of the BCLC stage B patients (intermediate HCC) and 33% of the BCLC stage C patients (advanced HCC) were treated according to the algorithm. Eighty-nine percent of the BCLC stage D patients (terminal HCC) were treated with best supportive care, as recommended. In 98 patients (44%) the performance status was disregarded in the stage assignment.Conclusion. The management of HCC in clinical practice frequently deviates from the BCLC recommendations. Most of the curative therapy options, which have well-defined selection criteria, were allocated according to the recommendations, while the majority of the palliative therapy options were assigned to patients with tumor stages not aligned with the recommendations. The only parameter which is subjective in the algorithm, the performance status, is also the least respected.
- Published
- 2016
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22. Exercise Attenuates the Transition from Fatty Liver to Steatohepatitis and Reduces Tumor Formation in Mice
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Maria Guarino, Pavitra Kumar, Andrea Felser, Luigi M. Terracciano, Sergi Guixé-Muntet, Bostjan Humar, Michelangelo Foti, Jean-Marc Nuoffer, Marie V. St-Pierre, and Jean-François Dufour
- Subjects
exercise ,ER stress ,non-alcoholic fatty liver disease (NAFLD) ,non-alcoholic steatohepatitis (NASH) ,hepatocellular carcinoma (HCC) ,liver fibrosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Non-alcoholic fatty liver disease (NAFLD) leads to steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. For sedentary patients, lifestyle interventions combining exercise and dietary changes are a cornerstone of treatment. However, the benefit of exercise alone when dietary changes have failed is uncertain. We query whether exercise alone arrests the progression of NASH and tumorigenesis in a choline-deficient, high-fat diet (CD-HFD) murine model. Male C57Bl/6N mice received a control diet or CD-HFD for 12 weeks. CD-HFD mice were randomized further for 8 weeks of sedentariness (SED) or treadmill exercise (EXE). CD-HFD for 12 weeks produced NAFL. After 20 weeks, SED mice developed NASH and hepatic adenomas. Exercise attenuated the progression to NASH. EXE livers showed lower triglycerides and tumor necrosis factor-α expression, less fibrosis, less ballooning, and a lower NAFLD activity score than did SED livers. Plasma transaminases and triglycerides were lower. Exercise activated AMP-activated protein kinase (AMPK) with inhibition of mTORC1 and decreased S6 phosphorylation, reducing hepatocellular adenoma. Exercise activated autophagy with increased LC3-II/LC3-I and mitochondrial recruitment of phosphorylated PTEN-induced kinase. Therefore, exercise attenuates the transition from NAFL to NASH, improves biochemical and histological parameters of NAFLD, and impedes the progression of fibrosis and tumorigenesis associated with enhanced activation of AMPK signaling and favors liver autophagy. Our work supports the benefits of exercise independently of dietary changes.
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- 2020
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23. Disruption of tumor suppressor gene Hint1 leads to remodeling of the lipid metabolic phenotype of mouse liver[S]
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Diren Beyoğlu, Kristopher W. Krausz, Juliette Martin, Olivier Maurhofer, Juliane Dorow, Uta Ceglarek, Frank J. Gonzalez, Jean-François Dufour, and Jeffrey R. Idle
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lipidomics ,metabolomics ,mass spectrometry ,carcinogenesis ,cholesterol ,phospholipids ,Biochemistry ,QD415-436 - Abstract
A lipidomic and metabolomic investigation of serum and liver from mice was performed to gain insight into the tumor suppressor gene Hint1. A major reprogramming of lipid homeostasis was found in both serum and liver of Hint1-null (Hint−/−) mice, with significant changes in the levels of many lipid molecules, as compared with gender-, age-, and strain-matched WT mice. In the Hint1−/− mice, serum total and esterified cholesterol were reduced 2.5-fold, and lysophosphatidylcholines (LPCs) and lysophosphatidic acids were 10-fold elevated in serum, with a corresponding fall in phosphatidylcholines (PCs). In the liver, MUFAs and PUFAs, including arachidonic acid (AA) and its metabolic precursors, were also raised, as was mRNA encoding enzymes involved in AA de novo synthesis. There was also a significant 50% increase in hepatic macrophages in the Hint1−/− mice. Several hepatic ceramides and acylcarnitines were decreased in the livers of Hint1−/− mice. The changes in serum LPCs and PCs were neither related to hepatic phospholipase A2 activity nor to mRNAs encoding lysophosphatidylcholine acetyltransferases 1-4. The lipidomic phenotype of the Hint1−/− mouse revealed decreased inflammatory eicosanoids with elevated proliferative mediators that, combined with decreased ceramide apoptosis signaling molecules, may contribute to the tumor suppressor activity of Hint1.
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- 2014
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24. Factors affecting screening for hepatocellular carcinoma
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Farah Al Hasani, Marina Knoepfli, Armin Gemperli, Attila Kollar, Vanessa Banz, Joachim Kettenbach, Peter Jüni, and Jean-François Dufour
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Cohort ,Cirrhosis ,Liver cancer ,Risk factor ,Surveillance ,Specialties of internal medicine ,RC581-951 - Abstract
Background and aim. Hepatocellular carcinoma (HCC) is a frequent cancer. Its prognosis is highly dependent on early diagnosis. Patients at risk for developing HCC should be enrolled in a surveillance programme. Nevertheless, many patients at risk are not regularly screened. We aimed at exploring the characteristics that affect enrolment in a surveillance programme.Material and methods. The characteristics of the patients included in the prospective Bern HCC cohort between August 2010 and August 2011 were analysed according to their participation in a surveillance programme.Results. Among the 82 patients included in the cohort during this period of time, 48 were in a surveillance program before the diagnosis of HCC. Thirty five percent of cirrhotic patients were not screened. Age, sex, level of education, Child-Pugh status and MELD score were similar between the patients who were screened and those who were not screened. Patients with a private insurance and patients treated by a liver specialist were more frequently enrolled in a surveillance program. Sixty seven percent of the screened patients were eligible for curative treatment whereas only 15% of the non-screened patients were.Conclusions. In conclusion the surveillance of patients at risk for developing HCC increases their chances to be diagnosed at an early stage to allow curative treatment. More than one third of cirrhotic patients were not regularly screened. Patients with chronic liver disease should be referred to identify those at risk and enrol them in a surveillance program.
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- 2014
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25. Nicotinamide and NAFLD: Is There Nothing New Under the Sun?
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Maria Guarino and Jean-François Dufour
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nicotinamide ,NAFLD ,steatosis ,Microbiology ,QR1-502 - Abstract
Nicotinamide adenine dinucleotide (NAD) has a critical role in cellular metabolism and energy homeostasis. Its importance has been established early with the discovery of NAD’s therapeutic role for pellagra. This review addresses some of the recent findings on NAD physiopathology and their effects on nonalcoholic fatty liver disease (NAFLD) pathogenesis, which need to be considered in the search for a better therapeutic approach. Reduced NAD concentrations contribute to the dysmetabolic imbalance and consequently to the pathogenesis of NAFLD. In this perspective, the dietary supplementation or the pharmacological modulation of NAD levels appear to be an attractive strategy. These reviewed studies open the doors to growing interest in NAD metabolism for NAFLD diagnosis, prevention, and treatment. Future rigorous clinical studies in humans will be necessary to validate these preliminary but promising results.
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- 2019
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26. Hepatitis C: a changing epidemic
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Gilles Wandeler, Jean-François Dufour, Philip Bruggmann, and Andri Rauch
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Epidemiology ,Viral Hepatitis C infection ,direct-acting antivirals ,HIV-coinfection ,eradication ,Medicine - Abstract
Approximately 3% of the world population is estimated to have a chronic hepatitis C virus (HCV) infection and 500,000 individuals die from its consequences yearly. Persons who inject drugs (PWID) bear the majority of the disease burden in high-income countries. Drug substitution programmes have helped reduce HCV transmissions among PWID. However, recent epidemics of sexually transmitted HCV infections in HIV-infected men who have sex with men demonstrated the changing nature of the HCV epidemic. HCV therapy is undergoing a revolution, as new interferon-free, oral treatments eradicate HCV infections in almost all treated patients. As a consequence, the eradication of HCV has become a matter of debate and is becoming an important future public health target. However, for this to be achieved, many challenges need to be addressed, including the poor uptake of HCV testing, the high cost of the new antiviral combinations and the high frequency of re-infections after treatment in some populations.
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- 2015
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27. Macro-AST in an asymptomatic young patient
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Haithem Chtioui, Olivier Mauerhofer, Beatrice Günther, and Jean-François Dufour
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Specialties of internal medicine ,RC581-951 - Published
- 2010
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28. Potentials and pitfalls of clinical peptidomics and metabolomics
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Alexander Benedikt Leichtle, Jean-François Dufour, and Georg Martin Fiedler
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bias ,bioinformatics ,data processing ,Interpretation ,metabolomics ,peptidomics ,Medicine - Abstract
Clinical peptidomics and metabolomics are two emerging “-omics” technologies with the potential not only to detect disease-specific markers, but also to give insight into the disease dependency of degradation processes and metabolic pathway alterations. However, despite their rapid evolution and major investments, a clinical breakthrough, such as the approval of a major cancer biomarker, is still out of sight. What are the reasons for this failure? In this review we focus on three important factors: sensitivity, specificity and the avoidance of bias. The way to clinical implementation of peptidomics and metabolomics is still hampered by many of the problems that had to be solved for genomics and proteomics in the past, as well as new ones that require the creation of new analytic, computational and interpretative techniques. The greatest challenge, however, will be the integration of information from different “-omics” subdisciplines into straightforward answers to clinical questions, for example, in the form of new, superior “meta-markers”.
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- 2013
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29. Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development.
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Christian M Lange, Daiki Miki, Hidenori Ochi, Hans-Dieter Nischalke, Jörg Bojunga, Stéphanie Bibert, Kenichi Morikawa, Jérôme Gouttenoire, Andreas Cerny, Jean-François Dufour, Meri Gorgievski-Hrisoho, Markus H Heim, Raffaele Malinverni, Beat Müllhaupt, Francesco Negro, David Semela, Zoltan Kutalik, Tobias Müller, Ulrich Spengler, Thomas Berg, Kazuaki Chayama, Darius Moradpour, Pierre-Yves Bochud, Hiroshima Liver Study Group, and Swiss Hepatitis C Cohort Study Group
- Subjects
Medicine ,Science - Abstract
Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3) serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657), GC (rs2282679), and DHCR7 (rs7944926, rs12785878) genotypes and 25(OH)D3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs) that are associated with reduced 25(OH)D3 serum levels were found to be associated with HCV-related HCC (P = 0.07 [OR = 1.13, 95% CI = 0.99-1.28] for CYP2R1, P = 0.007 [OR = 1.56, 95% CI = 1.12-2.15] for GC, P = 0.003 [OR = 1.42, 95% CI = 1.13-1.78] for DHCR7; ORs for risk genotypes). In contrast, no association between these genetic variations and liver fibrosis progression rate (P>0.2 for each SNP) or outcome of standard therapy with pegylated interferon-α and ribavirin (P>0.2 for each SNP) was observed, suggesting a specific influence of the genetic determinants of 25(OH)D3 serum levels on hepatocarcinogenesis.Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.
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- 2013
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30. Surveillance for Hepatocellular Carcinoma in Patients with NASH
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Philippe Kolly and Jean-François Dufour
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HCC ,NASH ,NAFLD ,surveillance ,screening ,Medicine (General) ,R5-920 - Abstract
European and American guidelines recommend surveillance for hepatocellular carcinoma (HCC) by performing ultrasonography on a six-month basis on an at risk population, defined by presence of cirrhosis. HCC, due to non-alcoholic steatohepatitis (NASH), is rising. Patients with NASH have a high risk of developing HCC and, therefore, have to be enrolled in a screening program. One of the challenges with NASH-induced HCC is that half of the cases arise in non-cirrhotic patients. There is a need to identify those patients in order to screen them for HCC. The obesity of these patients is another challenge, it makes ultrasound screening more difficult. Other radiological methods, such as computer tomography (CT) scans or magnetic resonance imaging (MRI), are available, but the surveillance program would no longer be cost-effective. There is a need to prospectively acquire information on cohorts of patients with NASH in order to improve the tools we have to diagnose early tumors in these patients.
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- 2016
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31. Liver tests: what to measure and what to do when abnormal
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Paraskevi Archanioti and Jean-François Dufour
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General Medicine - Published
- 2022
32. Use of statins after liver transplantation is associated with improved survival: results of a nationwide study
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Chiara, Becchetti, Melisa, Dirchwolf, Jonas, Schropp, Giulia, Magini, Beat, Müllhaupt, Franz, Immer, Jean-François, Dufour, Vanessa, Banz, Annalisa, Berzigotti, Jaume, Bosch, Patrick, Yerly, University of Zurich, and Bosch, Jaume
- Subjects
Adult ,Male ,610 Medicine & health ,360 Social problems & social services ,Risk Factors ,Humans ,2736 Pharmacology (medical) ,2715 Gastroenterology ,Pharmacology (medical) ,Aged ,Retrospective Studies ,Hepatology ,Graft Survival ,360 Soziale Probleme, Sozialdienste ,Gastroenterology ,Middle Aged ,Liver Transplantation ,Treatment Outcome ,10219 Clinic for Gastroenterology and Hepatology ,10036 Medical Clinic ,10032 Clinic for Oncology and Hematology ,10209 Clinic for Cardiology ,2721 Hepatology ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,10178 Clinic for Pneumology ,610 Medizin und Gesundheit - Abstract
BACKGROUND There is limited information on the effects of statins on the outcomes of liver transplantation (LT), regarding either their use by LT recipients or donors. AIM To analyse the association between statin exposure and recipient and graft survival. METHODS We included adult LT recipients with deceased donors in a nationwide prospective database study. Using a multistate modelling approach, we examined the effect of statins on the transition hazard between LT, biliary and vascular complications and death, allowing for recurring events. The observation time was 3 years. RESULTS We included 998 (696 male, 70%, mean age 54.46 ± 11.14 years) LT recipients. 14% of donors and 19% of recipients were exposed to statins during the study period. During follow-up, 141 patients died; there were 40 re-LT and 363 complications, with 66 patients having two or more complications. Treatment with statins in the recipient was modelled as a concurrent covariate and associated with lower mortality after LT (HR = 0.35; 95% CI 0.12-0.98; p = 0.047), as well as a significant reduction of re-LT (p = 0.004). However, it was not associated with lower incidence of complications (HR = 1.25; 95% CI = 0.85-1.83; p = 0.266). Moreover, in patients developing complications, statin use was significantly associated with decreased mortality (HR = 0.10; 95% CI = 0.01-0.81; p = 0.030), and reduced recurrence of complications (HR = 0.43; 95% CI = 0.20-0.93; p = 0.032). CONCLUSIONS Statin use by LT recipients may confer a survival advantage. Statin administration should be encouraged in LT recipients when clinically indicated.
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- 2022
33. Intermittent fasting- the future treatment in nash patients?
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Iulia Minciună, Suchira Gallage, Mathias Heikenwalder, Shira Zelber-Sagi, and Jean-François Dufour
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Hepatology - Published
- 2023
34. Supplementary Figure 4 from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
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Jean-François Dufour, Valentin Djonov, Luigi Terracciano, Maresa Afthinos, Vesna Radojevic, Paul M.J. McSheehy, Marie V. St-Pierre, Ruslan Hlushchuk, Bettina Saar, and Anne-Christine Piguet
- Abstract
Supplementary Figure 4 from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
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- 2023
35. Supplementary Figure 2 from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
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Jean-François Dufour, Valentin Djonov, Luigi Terracciano, Maresa Afthinos, Vesna Radojevic, Paul M.J. McSheehy, Marie V. St-Pierre, Ruslan Hlushchuk, Bettina Saar, and Anne-Christine Piguet
- Abstract
Supplementary Figure 2 from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
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- 2023
36. Supplementary Figure Legends from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
- Author
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Jean-François Dufour, Valentin Djonov, Luigi Terracciano, Maresa Afthinos, Vesna Radojevic, Paul M.J. McSheehy, Marie V. St-Pierre, Ruslan Hlushchuk, Bettina Saar, and Anne-Christine Piguet
- Abstract
Supplementary Figure Legends from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
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- 2023
37. Data from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
- Author
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Jean-François Dufour, Valentin Djonov, Luigi Terracciano, Maresa Afthinos, Vesna Radojevic, Paul M.J. McSheehy, Marie V. St-Pierre, Ruslan Hlushchuk, Bettina Saar, and Anne-Christine Piguet
- Abstract
Sorafenib targets the Raf/mitogen-activated protein kinase, VEGF, and platelet-derived growth factor pathways and prolongs survival patients in advanced hepatocellular carcinoma (HCC). Everolimus inhibits the mammalian target of rapamycin, a kinase overactive in HCC. To investigate whether the antitumor effects of these agents are additive, we compared a combined and sequential treatment regimen of everolimus and sorafenib with monotherapy. After hepatic implantation of Morris Hepatoma (MH) cells, rats were randomly allocated to everolimus (5 mg/kg, 2×/week), sorafenib (7.5 mg/kg/d), combined everolimus and sorafenib, sequential sorafenib (2 weeks) then everolimus (3 weeks), or control groups. MRI quantified tumor volumes. Erk1/2, 4E-BP1, and their phosphorylated forms were quantified by immunoblotting. Angiogenesis was assessed in vitro by aortic ring and tube formation assays, and in vivo with Vegf-a mRNA and vascular casts. After 35 days, tumor volumes were reduced by 60%, 85%, and 55%, relative to controls, in everolimus, the combination, and sequential groups, respectively (P < 0.01). Survival was longest in the combination group (P < 0.001). Phosphorylation of 4E-BP1 and Erk1/2 decreased after everolimus and sorafenib, respectively. Angiogenesis decreased after all treatments (P < 0.05), although sorafenib increased Vegf-a mRNA in liver tumors. Vessel sprouting was abundant in control tumors, lower after sorafenib, and absent after the combination. Intussusceptive angiogenic transluminal pillars failed to coalesce after the combination. Combined treatment with everolimus and sorafenib exerts a stronger antitumoral effect on MH tumors than monotherapy. Everolimus retains antitumoral properties when administered sequentially after sorafenib. This supports the clinical use of everolimus in HCC, both in combination with sorafenib or after sorafenib. Mol Cancer Ther; 10(6); 1007–17. ©2011 AACR.
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- 2023
38. Supplementary Figure 3 from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
- Author
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Jean-François Dufour, Valentin Djonov, Luigi Terracciano, Maresa Afthinos, Vesna Radojevic, Paul M.J. McSheehy, Marie V. St-Pierre, Ruslan Hlushchuk, Bettina Saar, and Anne-Christine Piguet
- Abstract
Supplementary Figure 3 from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
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- 2023
39. Supplementary Figure 1 from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
- Author
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Jean-François Dufour, Valentin Djonov, Luigi Terracciano, Maresa Afthinos, Vesna Radojevic, Paul M.J. McSheehy, Marie V. St-Pierre, Ruslan Hlushchuk, Bettina Saar, and Anne-Christine Piguet
- Abstract
Supplementary Figure 1 from Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma
- Published
- 2023
40. Validation of the Blood Test MACK-3 for the Noninvasive Diagnosis of Fibrotic Nonalcoholic Steatohepatitis: An International Study With 1924 Patients
- Author
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Clémence M. Canivet, Ming-Hua Zheng, Sami Qadri, Luisa Vonghia, Kee-Huat Chuah, Charlotte Costentin, Jacob George, Angelo Armandi, Leon A. Adams, Naomi F. Lange, Odile Blanchet, Valérie Moal, Ramy Younes, Marine Roux, Wah-Kheong Chan, Nathalie Sturm, Mohammed Eslam, Elisabetta Bugianesi, Zhengyi Wang, Jean-François Dufour, Sven Francque, Hannele Yki-Järvinen, Kenneth I. Zheng, and Jérôme Boursier
- Subjects
Hepatology ,Gastroenterology - Published
- 2023
41. Review article: vascular effects of <scp>PPARs</scp> in the context of <scp>NASH</scp>
- Author
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Sergi Guixé‐Muntet, Louise Biquard, Gyongyi Szabo, Jean‐François Dufour, Frank Tacke, Sven Francque, Pierre‐Emmanuel Rautou, and Jordi Gracia‐Sancho
- Subjects
Hepatology ,Pharmacology. Therapy ,Peroxisome Proliferator-Activated Receptors ,Gastroenterology ,nutritional and metabolic diseases ,digestive system ,digestive system diseases ,Diabetes Mellitus, Type 2 ,Liver ,Cardiovascular Diseases ,Non-alcoholic Fatty Liver Disease ,Humans ,Pharmacology (medical) ,Human medicine - Abstract
Background Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors known to regulate glucose and fatty acid metabolism, inflammation, endothelial function and fibrosis. PPAR isoforms have been extensively studied in metabolic diseases, including type 2 diabetes and cardiovascular diseases. Recent data extend the key role of PPARs to liver diseases coursing with vascular dysfunction, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Aim This review summarises and discusses the pathobiological role of PPARs in cardiovascular diseases with a special focus on their impact and therapeutic potential in NAFLD and NASH. Results and Conclusions PPARs may be attractive for the treatment of NASH due to their liver-specific effects but also because of their efficacy in improving cardiovascular outcomes, which may later impact liver disease. Assessment of cardiovascular disease in the context of NASH trials is, therefore, of the utmost importance, both from a safety and efficacy perspective.
- Published
- 2022
42. Data from Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Plasma Metabolomics and Lipid Profiling
- Author
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Jeffrey R. Idle, Jean-François Dufour, Frank J. Gonzalez, Thomas Pabst, Kristopher W. Krausz, Christian Lanz, Diren Beyoğlu, Olivier Maurhofer, and Andrew D. Patterson
- Abstract
There has been limited analysis of the effects of hepatocellular carcinoma (HCC) on liver metabolism and circulating endogenous metabolites. Here, we report the findings of a plasma metabolomic investigation of HCC patients by ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), random forests machine learning algorithm, and multivariate data analysis. Control subjects included healthy individuals as well as patients with liver cirrhosis or acute myeloid leukemia. We found that HCC was associated with increased plasma levels of glycodeoxycholate, deoxycholate 3-sulfate, and bilirubin. Accurate mass measurement also indicated upregulation of biliverdin and the fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochol-4,6-dien-24-oic acid in HCC patients. A quantitative lipid profiling of patient plasma was also conducted by ultraperformance liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (UPLC-ESI-TQMS). By this method, we found that HCC was also associated with reduced levels of lysophosphocholines and in 4 of 20 patients with increased levels of lysophosphatidic acid [LPA(16:0)], where it correlated with plasma α-fetoprotein levels. Interestingly, when fatty acids were quantitatively profiled by gas chromatography-mass spectrometry (GC-MS), we found that lignoceric acid (24:0) and nervonic acid (24:1) were virtually absent from HCC plasma. Overall, this investigation illustrates the power of the new discovery technologies represented in the UPLC-ESI-QTOFMS platform combined with the targeted, quantitative platforms of UPLC-ESI-TQMS and GC-MS for conducting metabolomic investigations that can engender new insights into cancer pathobiology. Cancer Res; 71(21); 6590–600. ©2011 AACR.
- Published
- 2023
43. Supplementary Figure 2 from Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Plasma Metabolomics and Lipid Profiling
- Author
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Jeffrey R. Idle, Jean-François Dufour, Frank J. Gonzalez, Thomas Pabst, Kristopher W. Krausz, Christian Lanz, Diren Beyoğlu, Olivier Maurhofer, and Andrew D. Patterson
- Abstract
PDF file - 1.3MB
- Published
- 2023
44. Supplementary Table 1 from Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Plasma Metabolomics and Lipid Profiling
- Author
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Jeffrey R. Idle, Jean-François Dufour, Frank J. Gonzalez, Thomas Pabst, Kristopher W. Krausz, Christian Lanz, Diren Beyoğlu, Olivier Maurhofer, and Andrew D. Patterson
- Abstract
PDF file - 63K
- Published
- 2023
45. 2D shear wave elastography of the rectus femoris muscle in patients with cirrhosis: feasibility and clinical findings. A pilot study
- Author
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Chiara Becchetti, Naomi F. Lange, Maria Gabriela Delgado, Michael P. Brönnimann, Martin H. Maurer, Jean-François Dufour, and Annalisa Berzigotti
- Subjects
Hepatology ,Gastroenterology ,610 Medicine & health - Abstract
BACKGROUND AND AIMS Frailty is frequent in cirrhosis and associated with skeletal muscle abnormalities and worse prognosis. 2D shear-wave elastography (2D-SWE) could mirror biomechanical properties of skeletal muscle reflecting muscle quality. However, there is no data on 2D-SWE on skeletal muscle stiffness assessment in cirrhosis and on frailty. METHODS Outpatients with cirrhosis were prospectively included in a single center. Skeletal muscle stiffness was studied at the rectus femoris by 2D-SWE. Ileo-psoas area and index (area/height2), and antero-posterior diameter of rectus femoris (RF) was measured on ultrasound. RESULTS We included 44 patients (24 male, age 59 [IQR 49-66]) with a median liver frailty index (LFI) of 3.7 (IQR 3.2-4.0). Measurement of RF muscle stiffness (RFMS) was feasible in all with high inter-measurement reproducibility. RFMS did not correlate with LFI, liver function and skeletal muscle diameters. Ileo-psoas index was lower in frail patients (1.7 vs 1.0 cm2/m2, p=0.024). RF antero-posterior diameter inversely correlated with LFI (r -0.578: p
- Published
- 2023
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46. Simulated IEEE 802.15.4a BER results (multipath and coexistence) in the spacecraft environment.
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Patrice Pelissou, Rémy Lachaud, Philippe Dallemagne, Jean-Dominique Decotignie, and Jean-François Dufour
- Published
- 2014
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47. Communication aspects in wireless passive sensing on spacecrafts.
- Author
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Pier Giorgio Arpesi, Claudia Sopranzi, Paolo Gamba, Emanuele Goldoni, Pietro Savazzi, Jean-François Dufour, and Michèle Lavagna
- Published
- 2014
- Full Text
- View/download PDF
48. Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention
- Author
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Pompilia Radu, Naomi Lange, and Jean-François Dufour
- Subjects
Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,610 Medicine & health ,Disease ,Chemoprevention ,digestive system ,Diabetes Complications ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Weight loss ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Obesity ,Life Style ,Aspirin ,Hepatology ,business.industry ,Liver Neoplasms ,Fatty liver ,nutritional and metabolic diseases ,medicine.disease ,digestive system diseases ,Metformin ,Hepatocellular carcinoma ,medicine.symptom ,Steatohepatitis ,610 Medizin und Gesundheit ,business ,Tertiary Prevention ,medicine.drug - Abstract
In many countries worldwide, the burden of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing. Preventive strategies are needed to counteract this trend. In this review, we provide an overview of the evidence on preventive strategies in NAFLD-associated HCC. We consider the impact of lifestyle factors such as weight loss, physical activity, smoking, dietary patterns and food items, including coffee and alcohol, on both HCC and NAFLD/NASH. Furthermore, evidence on chemopreventive treatments, including aspirin, antidiabetic treatments and statins is summarised. The role of adjuvant therapies for tertiary prevention of HCC is briefly reviewed.
- Published
- 2021
49. UWB radio channel characterization and design for intra spacecraft communication.
- Author
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Johan H. C. van den Heuvel, Jac Romme, Jean-François Dufour, Guido Dolmans, Nauman F. Kiyani, Kathleen Philips, and Harmke de Groot
- Published
- 2013
- Full Text
- View/download PDF
50. Wireless passive sensors for remote sensing of temperature on aerospace platforms.
- Author
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Paolo Gamba, Emanuele Goldoni, Pietro Savazzi, Pier Giorgio Arpesi, Claudia Sopranzi, and Jean-François Dufour
- Published
- 2013
- Full Text
- View/download PDF
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