75 results on '"Raevens, S."'
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2. Hepatopulmonary Syndrome and Portopulmonary Hypertension
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Raevens, S., primary and Colle, I., additional
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- 2017
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3. List of Contributors
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Abenavoli, L., primary, Abraldes, J.G., additional, Aguilar-Olivos, N.E., additional, Aguirre-García, J., additional, Almeda-Valdés, P., additional, Arauz, J., additional, Aravalli, R.N., additional, Arellanes-Robledo, J., additional, Ascensão, A., additional, Bardia, A., additional, Beleza, J., additional, Billiar, T.R., additional, Buendía-Montaño, L.D., additional, Camacho, J., additional, Casas-Grajales, S., additional, Casillas-Ramírez, A., additional, Castañeda-Hernández, G., additional, Cederbaum, A.I., additional, Chagoya de Sánchez, V., additional, Chávez, E., additional, Colle, I., additional, Cruz-Antonio, L., additional, Cruz-Baquero, A., additional, Czaja, A.J., additional, Dara, L., additional, del Pilar Cabrales-Romero, M., additional, Dhayal, M., additional, Espinosa-Cantellano, M., additional, Factor, V.M., additional, Ferenci, P., additional, Fernández-Martínez, E., additional, Fernandez, M., additional, Fierro, N.A., additional, Flores-Beltrán, R.E., additional, French, S.W., additional, Fu, P., additional, Fukui, H., additional, Galicia-Moreno, M., additional, Galli, A., additional, García-López, P., additional, Garcia-Tsao, G., additional, García de León, M.C., additional, Ginès, P., additional, Girish, C., additional, Gómez-Quiroz, L.E., additional, Gonçalves, I.O., additional, Gonzalez-Aldaco, K., additional, Gracia-Sancho, J., additional, Grattagliano, I., additional, Graupera, I., additional, Gressner, O.A., additional, Gressner, A.M., additional, Groszmann, R.J., additional, Guízar-Sahagún, G., additional, Gutiérrez-Reyes, D.G., additional, Gutiérrez-Ruiz, M.C., additional, Habeeb, M.A., additional, Hai, H., additional, Hammerich, L., additional, Hernández-Aquino, E., additional, Hernández, C., additional, Jaeschke, H., additional, Jiménez-Castro, M.B., additional, Kaplowitz, N., additional, Katoonizadeh, A., additional, Kawada, N., additional, Kershenobich, D., additional, Khan, A.A., additional, Ki, S.H., additional, Kim, K.M., additional, Lakshman, M.R., additional, Li, W., additional, Liang, X., additional, Liu, X., additional, Liu, Z.-X., additional, Loughran, P.A., additional, Lu, S.C., additional, Maeda, S., additional, Magalhães, J., additional, Mann, J., additional, Marquardt, J.U., additional, Martínez-Castillo, M., additional, Martínez-Chantar, M.L., additional, Martínez-Padrón, H.Y., additional, Martínez-Palomo, A., additional, Martins, M.J., additional, Mato, J.M., additional, Méndez-Sánchez, N., additional, Milic, N., additional, Montes-Páez, G., additional, Montes, S., additional, Muriel, P., additional, Nakamura, T., additional, Noureddin, M., additional, Oliveira, P.J., additional, Pacheco-Rivera, R., additional, Pacheco-Yépez, J., additional, Panduro, A., additional, Peralta, C., additional, Pérez-Carreón, J.I., additional, Portincasa, P., additional, Pradhan, S.C., additional, Raevens, S., additional, Ramachandran, A., additional, Ramos-Tovar, E., additional, Reyes-Gordillo, K., additional, Rivera-Mancía, S., additional, Roberts, M.S., additional, Rocha-Sánchez, A.Y., additional, Roman, S., additional, Serrano-Luna, J., additional, Shah, R., additional, Shibata, W., additional, Shibayama, M., additional, Shimizu, Y., additional, Shiota, G., additional, Solà, E., additional, Tacke, F., additional, Tajiri, K., additional, Takaki, A., additional, Tarocchi, M., additional, Thorgeirsson, S.S., additional, Thuy, T.T.V., additional, Thuy le, T.T., additional, Torimura, T., additional, Tristán-López, L.A., additional, Tsutsumi, V., additional, Tsutsumi, G.R., additional, Uchida, D., additional, Ueno, T., additional, Uribe, M., additional, Vargas-Pozada, E.E., additional, Vázquez-Flores, L.F., additional, Velasco-Loyden, G., additional, Vergani, L., additional, Vishwakarma, S.K., additional, Vorobioff, J.D., additional, Wang, J.-Y., additional, Wang, H., additional, Wu, S.-D., additional, Xia, F., additional, Xu, W., additional, Xu, L., additional, Yamamoto, K., additional, Yao, X.R., additional, Yu, J., additional, Zeng, L., additional, and Zhou, B.J., additional
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- 2017
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4. Recent advances in the approach to hepatopulmonary syndrome and portopulmonary hypertension
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Raevens, S, primary, Geerts, A, additional, Devisscher, L, additional, Van Vlierberghe, H, additional, Van Steenkiste, C, additional, and Colle, I, additional
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- 2021
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5. Chapter 39 - Hepatopulmonary Syndrome and Portopulmonary Hypertension
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Raevens, S. and Colle, I.
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- 2017
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6. An unusual cause of portal hypertension.
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Ferdinande, K., Lamiroy, T., Hoorens, A., Verhelst, X., Degroote, H., Raevens, S., Van Vlierberghe, H., and Geerts, A.
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- 2023
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7. A remarkable presentation of a massive Budd-Chiari syndrome.
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Ferdinande, K., Degroote, H., Geerts, A., Van Vlierberghe, H., Verhelst, X., and Raevens, S.
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- 2023
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8. Cu isotope ratio shifts in common bile duct ligated mice and correlates with the degree of cholestatic-induced liver disease
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Campenhout, S.V., primary, Costas-Rodríguez, M., additional, Hastuti, A.A.M.B., additional, Raevens, S., additional, Geerts, A., additional, Verhelst, X., additional, Vanhaecke, F., additional, Vlierberghe, H.V., additional, and Devisscher, L., additional
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- 2018
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9. Angiopoietin-2 as therapeutic target for pathological angiogenesis and inflammation in non-alcoholic steatohepatitis
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Lefere, S., primary, Van de Velde, F., additional, Raevens, S., additional, Van Campenhout, S., additional, Vandierendonck, A., additional, Neyt, S., additional, Vanhove, C., additional, Hoorens, A., additional, Casteleyn, C., additional, Verhelst, X., additional, Van Vlierberghe, H., additional, Lapauw, B., additional, Geerts, A., additional, and Devisscher, L., additional
- Published
- 2018
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10. Serum vascular cell adhesion molecule-1 predicts significant liver fibrosis in non-alcoholic fatty liver disease
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Lefere, S, primary, Van de Velde, F, additional, Devisscher, L, additional, Bekaert, M, additional, Raevens, S, additional, Verhelst, X, additional, Van Nieuwenhove, Y, additional, Praet, M, additional, Hoorens, A, additional, Van Steenkiste, C, additional, Van Vlierberghe, H, additional, Lapauw, B, additional, and Geerts, A, additional
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- 2017
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11. Kupffer cell pool is maintained by local proliferation and the differentiation of bone marrow monocytes into short-lived monocyte-derived Kupffer cells during non-alcoholic steatohepatitis and recovery
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Devisscher, L., primary, Scott, C.L., additional, Lefere, S., additional, Raevens, S., additional, Bogaerts, E., additional, Paridaens, A., additional, Verhelst, X., additional, Geerts, A., additional, Guilliams, M., additional, and Van Vlierberghe, H., additional
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- 2017
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12. Serum vascular cell adhesion molecule-1 predicts significant liver fibrosis in obese patients with non-alcoholic fatty liver disease
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Lefere, S., primary, Van de Velde, F., additional, Devisscher, L., additional, Bekaert, M., additional, Raevens, S., additional, Verhelst, X., additional, Van Nieuwenhove, Y., additional, Praet, M., additional, Hoorens, A., additional, Van Steenkiste, C., additional, Van Vlierberghe, H., additional, Lapauw, B., additional, and Geerts, A., additional
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- 2017
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13. Kinetics of Pulmonary Angiogenesis in Mouse Common Bile Duct Ligation-Induced Liver Fibrosis
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Raevens, S., primary, Devisscher, L., additional, Paridaens, A., additional, Bogaerts, E., additional, Lefere, S., additional, Vandewynckel, Y.-P., additional, Casteleyn, C., additional, Bracke, K., additional, Maes, T., additional, Verhelst, X., additional, Van Vlierberghe, H., additional, Van Steenkiste, C., additional, Geerts, A., additional, and Colle, I., additional
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- 2016
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14. The Bile Acid Tauroursodeoxycholic Acid Cooperates with N-Acetylcysteine in the Treatment of Experimental Acetaminophen-Induced Hepatotoxicity
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Paridaens, A., primary, Devisscher, L., additional, Raevens, S., additional, Bogaerts, E., additional, Vandewynckel, Y.-P., additional, Verhelst, X., additional, Mannaerts, I., additional, Van Grunsven, L., additional, Van Vlierberghe, H., additional, Colle, I., additional, and Geerts, A., additional
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- 2016
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15. The Unfolded Protein Response Underlies Microenvironmental Stress-Induced Phenotype Switching Leading to Stemness and Chemoresistance in Human Hepatocellular Carcinoma
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Vandewynckel, Y.-P., primary, Govaere, O., additional, Vandierendonck, A., additional, Laukens, D., additional, Devisscher, L., additional, Paridaens, A., additional, Bogaerts, E., additional, Raevens, S., additional, Verhelst, X., additional, Van Steenkiste, C., additional, Libbrecht, L., additional, Ampe, C., additional, Van Troys, M., additional, Geerts, A., additional, Roskams, T., additional, and Van Vlierberghe, H., additional
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- 2016
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16. Next-Generation Proteasome Inhibitor Oprozomib Synergizes with Modulators of the Unfolded Protein Response to Suppress Hepatocellular Carcinoma
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Vandewynckel, Y.-P., primary, Coucke, C., additional, Laukens, D., additional, Devisscher, L., additional, Paridaens, A., additional, Bogaerts, E., additional, Vandierendonck, A., additional, Raevens, S., additional, Verhelst, X., additional, Van Steenkiste, C., additional, Libbrecht, L., additional, Geerts, A., additional, and Van Vlierberghe, H., additional
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- 2016
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17. FRI-212 - Cu isotope ratio shifts in common bile duct ligated mice and correlates with the degree of cholestatic-induced liver disease
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Campenhout, S.V., Costas-Rodríguez, M., Hastuti, A.A.M.B., Raevens, S., Geerts, A., Verhelst, X., Vanhaecke, F., Vlierberghe, H.V., and Devisscher, L.
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- 2018
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18. THU-443 - Angiopoietin-2 as therapeutic target for pathological angiogenesis and inflammation in non-alcoholic steatohepatitis
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Lefere, S., Van de Velde, F., Raevens, S., Van Campenhout, S., Vandierendonck, A., Neyt, S., Vanhove, C., Hoorens, A., Casteleyn, C., Verhelst, X., Van Vlierberghe, H., Lapauw, B., Geerts, A., and Devisscher, L.
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- 2018
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19. P0290 : Placental growth factor inhibition modulates the interplay between hypoxia and the unfolded protein response in hepatocellular carcinoma
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Vandewynckel, Y.-P., primary, Laukens, D., additional, Devisscher, L., additional, Paridaens, A., additional, Bogaerts, E., additional, Verhelst, X., additional, Van den Bussche, A., additional, Raevens, S., additional, Van Steenkiste, C., additional, Jonckx, B., additional, Libbrecht, L., additional, Geerts, A., additional, Carmeliet, P., additional, and Van Vlierberghe, H., additional
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- 2015
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20. P0258 : Tauroursodeoxycholic acid dampens oncogenic apoptosis induced by endoplasmic reticulum stress during hepatocarcinogen exposure
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Vandewynckel, Y.-P., primary, Laukens, D., additional, Devisscher, L., additional, Paridaens, A., additional, Bogaerts, E., additional, Verhelst, X., additional, Van den Bussche, A., additional, Raevens, S., additional, Van Steenkiste, C., additional, Van Troys, M., additional, Ampe, C., additional, Descamps, B., additional, Vanhove, C., additional, Govaere, O., additional, Libbrecht, L., additional, Geerts, A., additional, and Van Vlierberghe, H., additional
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- 2015
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21. FRI-100 - Next-Generation Proteasome Inhibitor Oprozomib Synergizes with Modulators of the Unfolded Protein Response to Suppress Hepatocellular Carcinoma
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Vandewynckel, Y.-P., Coucke, C., Laukens, D., Devisscher, L., Paridaens, A., Bogaerts, E., Vandierendonck, A., Raevens, S., Verhelst, X., Van Steenkiste, C., Libbrecht, L., Geerts, A., and Van Vlierberghe, H.
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- 2016
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22. FRI-101 - The Unfolded Protein Response Underlies Microenvironmental Stress-Induced Phenotype Switching Leading to Stemness and Chemoresistance in Human Hepatocellular Carcinoma
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Vandewynckel, Y.-P., Govaere, O., Vandierendonck, A., Laukens, D., Devisscher, L., Paridaens, A., Bogaerts, E., Raevens, S., Verhelst, X., Van Steenkiste, C., Libbrecht, L., Ampe, C., Van Troys, M., Geerts, A., Roskams, T., and Van Vlierberghe, H.
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- 2016
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23. FRI-022 - Kinetics of Pulmonary Angiogenesis in Mouse Common Bile Duct Ligation-Induced Liver Fibrosis
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Raevens, S., Devisscher, L., Paridaens, A., Bogaerts, E., Lefere, S., Vandewynckel, Y.-P., Casteleyn, C., Bracke, K., Maes, T., Verhelst, X., Van Vlierberghe, H., Van Steenkiste, C., Geerts, A., and Colle, I.
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- 2016
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24. THU-278 - The Bile Acid Tauroursodeoxycholic Acid Cooperates with N-Acetylcysteine in the Treatment of Experimental Acetaminophen-Induced Hepatotoxicity
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Paridaens, A., Devisscher, L., Raevens, S., Bogaerts, E., Vandewynckel, Y.-P., Verhelst, X., Mannaerts, I., Van Grunsven, L., Van Vlierberghe, H., Colle, I., and Geerts, A.
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- 2016
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25. Reduced temperature flip-chip technologies on flexible display substrates using adhesives.
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Vanfleteren, J., Vandecasteele, B., Raevens, S., Maattanen, J., and Perttula, P.
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- 2002
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26. Reduced temperature flip-chip technologies on flexible display substrates using adhesives
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Vanfleteren, J., primary, Vandecasteele, B., additional, Raevens, S., additional, Maattanen, J., additional, and Perttula, P., additional
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27. Refractory subacute steatohepatitis after biliopancreatic diversion
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Hans Van Vlierberghe, Anne Hoorens, Sarah Raevens, Anja Geerts, Xavier Verhelst, Roberto Troisi, Sander Lefere, Lefere, S., Hoorens, A., Raevens, S., Troisi, R., Verhelst, X., Van Vlierberghe, H., and Geerts, A.
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Liver transplantation ,medicine.disease ,Biliopancreatic Diversion ,Gastroenterology ,Fatty Liver ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Fatal Outcome ,Postoperative Complications ,Refractory ,Recurrence ,Internal medicine ,medicine ,Humans ,030211 gastroenterology & hepatology ,Female ,Steatohepatitis ,business - Published
- 2017
28. Adipose Tissue Insulin Resistance Correlates with Disease Severity in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease: A Prospective Cohort Study.
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Heldens A, Dupont E, Devisscher L, Buytaert M, Verhelst X, Raevens S, Van Vlierberghe H, Geerts A, De Bruyne R, and Lefere S
- Abstract
Objectives: To assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR evolution during a lifestyle intervention program., Study Design: In this prospective cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound examination and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4-6 months, anthropometric measurements, serum biochemical analysis, ultrasound examination, and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration, and hepatic IR by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), respectively., Results: Of 200 patients with obesity, 56% had evidence of steatosis on ultrasound examination and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already increased in patients with only mild steatosis (P = .0403). Patients with more insulin-sensitive adipose tissue exhibited a lower liver fat content (P < .05) and serum alanine transaminase levels (P = .001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (P < .001), but not with total body fat percentage (P = .263). After 4-6 months of lifestyle management, both MASLD and Adipo-IR improved., Conclusions: Our data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis., Competing Interests: Declaration of Competing Interest Work in the lab of A.G. and S.L. has received funding from Inventiva. The other authors declare not conflicts of interest. Supported by a grant from the Ghent University Hospital (FIKO19-TYPE2-006). S.L. is supported by a grant from the Research Foundation – Flanders (FWO) (1227824N). H.V., A.G., and R.B. are senior clinical investigators of the FWO (1801721N, 1805718N and 1843824N). These funding agencies were not involved in study design, analysis or reporting., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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29. External validation of the IAIHG autoimmune hepatitis response criteria in a multicentric real-world cohort.
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Grossar L, Raevens S, Van Steenkiste C, Colle I, De Vloo C, Orlent H, Schouten J, Gallant M, Van Driessche A, Lefere S, Devisscher L, Geerts A, Van Vlierberghe H, and Verhelst X
- Abstract
Background & Aims: The goal of treatment in autoimmune hepatitis (AIH) is induction of remission to prevent the development of liver fibrosis, cirrhosis, and its related complications. Various definitions of treatment response and remission have been used. The International Autoimmune Hepatitis Group (IAIHG) recently defined consensus criteria for treatment response. We aimed to validate the IAIHG response criteria in our cohort and establish correlations with survival endpoints., Methods: We performed a retrospective, multicentric cohort study in one tertiary and seven secondary care centres in Belgium. Eligible patients were at least 18 years of age at data collection and were diagnosed with AIH by a simplified IAIHG score of ≥6. Complete biochemical response (CBR) was defined according to the IAIHG consensus criteria as normalisation of transaminases and serum IgG within the first 6 months of treatment. The primary endpoint was liver-related survival - defined as freedom from liver-related death or liver transplantation. Secondary endpoints were overall mortality and transplant-free survival. Outcomes were compared between patients attaining CBR and those with insufficient response., Results: Biochemical response status could be determined in 200 patients with AIH: CBR was achieved in 128 (64.0%) individuals. Patients not achieving CBR more frequently presented with cirrhosis on initial histology (22.2% vs . 10.9%, p = 0.036). Liver-related mortality or liver transplantation as a primary outcome occurred in 26 patients (13.0%). Patients achieving CBR exhibited superior liver-related (hazard ratio 0.118; 95% CI 0.052-0.267; p <0.0001) and overall (hazard ratio 0.253; 95% CI 0.111-0.572; p = 0.0003) survival., Conclusions: We externally validated the IAIHG consensus criteria for CBR and confirmed their correlation with survival endpoints in a multicentric, real-world cohort. Patients with AIH achieving CBR as an intermediate endpoint have significantly superior liver-related and overall survival., Impacts and Implications: Corticosteroids remain the cornerstone of treatment to induce remission of disease activity in autoimmune hepatitis (AIH), and the majority of patients require long-term corticosteroid treatment to achieve sustained remission. Definitions of response to treatment have varied over the years, and consistently used intermediate endpoints are needed to facilitate advancements in non-corticosteroid treatment for autoimmune hepatitis. The International Autoimmune Hepatitis Group (IAIHG) defined consensus criteria on endpoints in the treatment of AIH, for which further external validation is needed. Here, we demonstrate the usefulness of the IAIHG consensus criteria and corroborate their correlation to primary endpoints, such as liver-related survival and native liver survival in a multicentric, real-world setting. The design of future studies can rely on the IAIHG consensus criteria as intermediate endpoints., (© 2024 The Authors.)
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- 2024
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30. PhpC modulates G-quadruplex-RNA landscapes in human cells.
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Mitteaux J, Raevens S, Wang Z, Pirrotta M, Valverde IE, Hudson RHE, and Monchaud D
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- Humans, DNA genetics, Ligands, RNA, G-Quadruplexes
- Abstract
Stabilizing DNA/RNA G-quadruplexes (G4s) using small molecules (ligands) has proven an efficient strategy to decipher G4 biology. Quite paradoxically, this search has also highlighted the need for finding molecules able to disrupt G4s to tackle G4-associated cellular dysfunctions. We report here on both qualitative and quantitative investigations that validate the G4-RNA-destabilizing properties of the leading compound PhpC in human cells.
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- 2024
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31. Systematic review: Glycomics as diagnostic markers for hepatocellular carcinoma.
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Butaye E, Somers N, Grossar L, Pauwels N, Lefere S, Devisscher L, Raevens S, Geerts A, Meuris L, Callewaert N, Van Vlierberghe H, and Verhelst X
- Subjects
- Humans, Glycomics, alpha-Fetoproteins analysis, Biomarkers, Glycoproteins, Biomarkers, Tumor, Liver Cirrhosis diagnosis, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular pathology, Liver Neoplasms diagnosis, Liver Neoplasms pathology
- Abstract
Background: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with one of the highest cancer-related mortality rates worldwide. Early diagnosis is crucial for improving the therapeutic options and reducing the disease-related mortality., Aim: To investigate serum N-glycomics as diagnostic markers for HCC., Methods: We performed a comprehensive search in PubMed, EMBASE, Web of Science and Scopus through August 17, 2023. Eligible studies assessed the potential use of serum N-glycomics as diagnostic biomarkers for HCC. Study selection, data extraction and quality assessment were performed by two independent reviewers., Results: Of the 48 articles included, 11 evaluated the utility of N-glycomics for the diagnosis of HCC in whole serum while the remaining articles focused on specific protein glycoforms or protein levels. Of these specific proteins, haptoglobin, alpha-fetoprotein (AFP), kininogen (Kin), α-1-antitrypsin and Golgi protein 73 (GP73) were the most frequently studied. Increased levels of fucosylation and branching presented as the most prevalent post-translational modifications of glycoproteins in patients with HCC compared to controls. Notably, glycomics-based biomarkers may provide a clinical benefit for the diagnosis of early HCC, as several algorithms achieved AUCs between 0.92-0.97. However, these were based on single studies with limited sample sizes and should therefore be validated., Conclusions: Alterations in serum N-glycomics, characterised by increased levels of fucosylation and branching, have potential as diagnostic biomarkers for HCC. Optimisation of study design, patient selection and analysing techniques are needed before clinical implementation will be possible., (© 2023 John Wiley & Sons Ltd.)
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- 2024
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32. Patients hospitalized with alcohol-related liver disease and prior bariatric surgery are more prone to develop acute-on-chronic liver failure.
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Onghena L, Van Nieuwenhove Y, Demeulenaere L, Devisscher L, Verhelst X, Degroote H, Raevens S, Van Vlierberghe H, Lefere S, and Geerts A
- Subjects
- Humans, Female, Male, Retrospective Studies, Hospitalization, Obesity, Morbid complications, Obesity, Morbid surgery, Obesity, Morbid epidemiology, Acute-On-Chronic Liver Failure complications, Bariatric Surgery adverse effects, Gastric Bypass
- Abstract
Background & Aims: Patients with a history of bariatric surgery (BS) are susceptible to developing alcohol use disorder. We and others have previously shown that these patients can develop severe alcohol-related liver disease (ARLD). Our aim was to describe the demographics, co-morbidities and mortality of a hospitalized population diagnosed with alcohol-related liver disease, in relation to BS., Methods: We included 299 patients hospitalized with ARLD at the Ghent University Hospital between 1 January 2018 and 31 December 2022. Clinical, biochemical and outcome data were retrospectively retrieved from the most recent hospitalization. Statistical analysis was performed using the t test, Mann-Whitney U and χ
2 tests., Results: Thirteen per cent (39/299) of patients admitted with ARLD had a history of bariatric surgery, of whom 25 (64.1%) had undergone Roux-en-Y gastric bypass. Patients with a history of BS were predominantly female (76.9%), in contrast to the non-BS population (29.2%) (p < .0001), and despite being significantly younger (p < .0001) and had a similar survival (61.5% vs. 58.1%). Bariatric surgery and older age at diagnosis were both significantly associated with poorer transplant-free survival. The cause of death was acute-on-chronic liver failure in 73.3% of BS patients, compared to only 19.2% of those without a history of BS (p < .0001). The weekly amount of alcohol consumed (p = .012) and duration of use (p < .0001) were significantly lower/shorter in the BS population., Conclusions: BS patients hospitalized with ARLD are predominantly younger women with a lower cumulative alcohol consumption compared to those without prior BS. BS impacted transplant-free survival, with ACLF as the predominant cause of death in these patients., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)- Published
- 2023
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33. Fingolimod as a sphingolipid modulator in hepatopulmonary syndrome: A critical review.
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Raevens S and Fallon MB
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- 2023
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34. Autophagy in liver regeneration: Unravelling the endothelial cell's role and therapeutic prospects.
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Raevens S
- Subjects
- Humans, Autophagy, Endothelial Cells, Liver Regeneration, Focal Nodular Hyperplasia
- Published
- 2023
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35. [1,2,4]triazolo[4,3- a ]quinoxaline as Novel Scaffold in the Imiqualines Family: Candidates with Cytotoxic Activities on Melanoma Cell Lines.
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Patinote C, Raevens S, Baumann A, Pellegrin E, Bonnet PA, and Deleuze-Masquéfa C
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- Humans, Quinoxalines pharmacology, Quinoxalines chemistry, Cell Line, Structure-Activity Relationship, Molecular Structure, Melanoma, Cutaneous Malignant, Melanoma drug therapy, Skin Neoplasms, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry
- Abstract
Cutaneous melanoma is one of the most aggressive human cancers and is the deadliest form of skin cancer, essentially due to metastases. Novel therapies are always required, since cutaneous melanoma develop resistance to oncogenic pathway inhibition treatment. The Imiqualine family is composed of heterocycles diversely substituted around imidazo[1,2- a ]quinoxaline, imidazo[1,2- a ]pyrazine, imidazo[1,5- a ]quinoxaline, and pyrazolo[1,5- a ]quinoxaline scaffolds, which display interesting activities on a panel of cancer cell lines, especially melanoma cell lines. We have designed and prepared novel compounds based on the [1,2,4]triazolo[4,3- a ]quinoxaline scaffold through a common synthetic route, using 1-chloro-2-hydrazinoquinoxaline and an appropriate aldehyde. Cyclization is ensured by an oxidation-reduction mechanism using chloranil. The substituents on positions 1 and 8 were chosen based on previous structure-activity relationship (SAR) studies conducted within our heterocyclic Imiqualine family. Physicochemical parameters of all compounds have also been predicted. A375 melanoma cell line viability has been evaluated for 16 compounds. Among them, three novel [1,2,4]triazolo[4,3- a ]quinoxalines display cytotoxic activities. Compounds 16a and 16b demonstrate relative activities in the micromolar range (respectively, 3158 nM and 3527 nM). Compound 17a shows the best EC
50 of the novel series (365 nM), even if EAPB02303 remains the lead of the entire Imiqualine family (3 nM).- Published
- 2023
- Full Text
- View/download PDF
36. Hepatopulmonary syndrome.
- Author
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Raevens S, Boret M, and Fallon MB
- Abstract
Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of liver disease, which adversely affects prognosis. The disease is characterised by intrapulmonary vascular dilatations and shunts, resulting in impaired gas exchange. A complex interaction between the liver, the gut and the lungs, predominately impacting pulmonary endothelial cells, immune cells and respiratory epithelial cells, is responsible for the development of typical pulmonary alterations seen in HPS. Liver transplantation is the only therapeutic option and generally reverses HPS. Since the implementation of the model for end-stage liver disease (MELD) standard exception policy, outcomes in patients with HPS have been significantly better than they were in the pre-MELD era. This review summarises current knowledge and highlights what's new regarding the diagnosis and management of HPS, and our understanding of pathogenesis based on experimental models and translational studies., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Authors.)
- Published
- 2022
- Full Text
- View/download PDF
37. Metallothioneins alter macrophage phenotype and represent novel therapeutic targets for acetaminophen-induced liver injury.
- Author
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Devisscher L, Van Campenhout S, Lefere S, Raevens S, Tilleman L, Van Nieuwerburgh F, Van Eeckhoutte HP, Hoorens A, Lynes MA, Geerts A, Laukens D, and Van Vlierberghe H
- Subjects
- Animals, Antibodies, Monoclonal therapeutic use, Chemical and Drug Induced Liver Injury drug therapy, Humans, Macrophages drug effects, Male, Mice, Mice, Inbred C57BL, Acetaminophen adverse effects, Analgesics, Non-Narcotic adverse effects, Chemical and Drug Induced Liver Injury pathology, Macrophages pathology, Metallothionein analysis
- Abstract
Acetaminophen (APAP) intoxication is the foremost cause of drug-induced liver failure in developed countries. The only pharmacologic treatment option, N-acetylcysteine (NAC), is not effective for patients who are admitted too late and/or who have excessive liver damage, emphasizing the need for alternative treatment options. APAP intoxication results in hepatocyte death and release of danger signals, which further contribute to liver injury, in part by hepatic monocyte/macrophage infiltration and activation. Metallothionein (MT) 1 and 2 have important danger signaling functions and might represent novel therapeutic targets in APAP overdose. Therefore, we evaluated hepatic MT expression and the effect of anti-MT antibodies on the transcriptional profile of the hepatic macrophage population and liver injury following APAP overdose in mice. Hepatic MT expression was significantly induced in APAP-intoxicated mice and abundantly present in human livers. APAP intoxication in mice resulted in increased serum transaminase levels, extended necrotic regions on liver histology and induced expression of proinflammatory markers, which was significantly less pronounced in mice treated with anti-MT antibodies. Anti-MT antibody therapy attenuated proinflammatory macrophage polarization, as demonstrated by RNA sequencing analyses of isolated liver macrophages and in LPS-stimulated bone marrow-derived macrophages. Importantly, NAC and anti-MT antibodies were equally effective whereas administration of anti-MT antibody in combination with NAC exceeded the efficiency of both monotherapies in APAP-induced liver injury (AILI). We conclude that the neutralization of secreted MTs using a monoclonal antibody is a novel therapeutic strategy as mono- or add-on therapy for AILI. In addition, we provide evidence suggesting that MTs in the extracellular environment are involved in macrophage polarization., (©2021 Society for Leukocyte Biology.)
- Published
- 2022
- Full Text
- View/download PDF
38. Liver Transplantation in Portopulmonary Hypertension: Another Piece of the Puzzle?
- Author
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Raevens S and Fallon MB
- Subjects
- Humans, Hypertension, Hypertension, Portal complications, Hypertension, Portal surgery, Liver Transplantation adverse effects
- Published
- 2021
- Full Text
- View/download PDF
39. Diagnosis of Hepatopulmonary Syndrome in a Large Integrated Health System.
- Author
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Bommena S, Gerkin RD, Agarwal S, Raevens S, Glassberg MK, and Fallon MB
- Subjects
- Blood Gas Analysis, Humans, Liver Cirrhosis complications, Liver Cirrhosis diagnosis, Retrospective Studies, Delivery of Health Care, Integrated, Hepatopulmonary Syndrome diagnosis
- Abstract
Background & Aims: Data on the accuracy of the diagnosis of hepatopulmonary syndrome (HPS) in cirrhosis is limited. We evaluated the clinical characteristics of patients with International Classification of Diseases (ICD) codes for hepatopulmonary syndrome (HPS) in a large integrated health system., Methods: A retrospective review of encounters was performed of all patients with ICD-9-CM and/or ICD-10-CM diagnosis of cirrhosis and HPS from 2014-2019 in a multi-state health system. Demographics and cardiopulmonary testing closest to the time of HPS diagnosis were recorded. HPS was defined using standard criteria., Results: A total of 42,749 unique individuals with cirrhosis were identified. An ICD diagnosis of HPS was found in 194 patients (0.45%), of which 182 had clinically confirmed cirrhosis. 143 (78.5%) underwent contrast-enhanced transthoracic echocardiography, and 98 (54%) had delayed shunting. Among them, 61 patients had a documented arterial blood gas, with 53 showing abnormal oxygenation (A-a gradient of >15 mm Hg). 12 were excluded due to significant pulmonary function test abnormalities and abnormal oxygenation from other cardiopulmonary diseases. Ultimately, 41 (22.5%) fulfilled the criteria for HPS. When stratifying those with an ICD code diagnosis of HPS into HPS, no HPS and indeterminate HPS groups, based on standard diagnostic criteria for HPS, we found that the confirmed HPS patients had similar complications except for less portopulmonary hypertension, worse gas exchange, less cardiopulmonary disease and were more often diagnosed in transplant centers., Conclusions: The diagnosis of HPS by ICD code is made in an extremely small subset of a sizeable cirrhotic cohort. When made, only a minority of these patients meet diagnostic criteria. Our findings highlight the need for improved education and more effective screening algorithms., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
40. Pulmonary Abnormalities in Liver Disease: Relevance to Transplantation and Outcome.
- Author
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Raevens S, Boret M, De Pauw M, Fallon MB, and Van Vlierberghe H
- Subjects
- Adult, Asthma diagnosis, Asthma epidemiology, Asthma mortality, COVID-19 diagnosis, COVID-19 epidemiology, COVID-19 mortality, COVID-19 virology, Child, Cystic Fibrosis, End Stage Liver Disease complications, Hepatopulmonary Syndrome diagnosis, Hepatopulmonary Syndrome epidemiology, Hepatopulmonary Syndrome mortality, Humans, Hypertension, Pulmonary drug therapy, Hypertension, Pulmonary etiology, Liver Transplantation methods, Lung Diseases epidemiology, Lung Diseases pathology, Lung Diseases physiopathology, Mass Screening, Patient Selection ethics, Prognosis, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive epidemiology, Pulmonary Disease, Chronic Obstructive mortality, Respiratory Function Tests methods, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Sarcoidosis diagnosis, Sarcoidosis epidemiology, Sarcoidosis mortality, Survival Rate trends, Telangiectasia, Hereditary Hemorrhagic diagnosis, Telangiectasia, Hereditary Hemorrhagic epidemiology, Telangiectasia, Hereditary Hemorrhagic mortality, alpha 1-Antitrypsin Deficiency diagnosis, alpha 1-Antitrypsin Deficiency epidemiology, alpha 1-Antitrypsin Deficiency mortality, Hypertension, Portal complications, Liver Cirrhosis complications, Liver Transplantation mortality, Lung Diseases complications
- Abstract
Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post-LT outcome. Pre-LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end-stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post-LT and are considered "pulmonary indications" for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1-antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post-LT survival, as well as the reciprocal impact of LT on the evolution of lung function., (© 2021 by the American Association for the Study of Liver Diseases.)
- Published
- 2021
- Full Text
- View/download PDF
41. Recent advances in the approach to hepatopulmonary syndrome and portopulmonary hypertension.
- Author
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Raevens S, Geerts A, Devisscher L, Van Vlierberghe H, Van Steenkiste C, and Colle I
- Subjects
- Humans, Liver Cirrhosis, Hepatopulmonary Syndrome diagnosis, Hepatopulmonary Syndrome therapy, Hypertension, Portal complications, Hypertension, Portal diagnosis, Hypertension, Portal therapy, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary etiology, Hypertension, Pulmonary therapy, Pulmonary Arterial Hypertension
- Abstract
Liver disease, cirrhosis and portal hypertension can be complicated by pulmonary vascular disease, which may affect prognosis and influence liver transplantation (LT) candidacy. Pulmonary vascular complications comprise hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). Although these two conditions develop on a same background and share a common trigger, pulmonary responses are distinct and occur at different anatomical sites of the pulmonary circulation. HPS affects 10-30% of patients referred for LT, and is characterized by gas exchange abnormalities due to pulmonary vasodilation and right-to-left shunting. POPH occurs in 5%, and is defined by pulmonary arterial hypertension due to increased pulmonary vascular resistance, which leads to hemodynamic failure. Even though HPS and POPH may have a substantial negative impact on survival, both entities are clinically underrecognized and frequently misdiagnosed. Without intervention, the 5-year survival rate is 23% in HPS and 14% in POPH. Their presence should be actively sought by organized screening in patients presenting with dyspnea and in all patients on the waitlist for LT, also because clinical symptoms are commonly non-specific or even absent. LT may lead to resolution, however, advanced stages of either HPS or POPH may jeopardize safe and successful LT. This implicates the need of proper identification of HPS and POPH cases, as well as the need to be able to successfully 'bridge' patients to LT by medical intervention. A review article on this topic has been published in this journal in 2007 (1). This updated review focuses on recent advances in the diagnosis and management of these 2 liver-induced pulmonary vascular disorders and incorporates results from our recent work., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)
- Published
- 2021
- Full Text
- View/download PDF
42. Vasomodulators and Liver Transplantation for Portopulmonary Hypertension: Evidence From a Systematic Review and Meta-Analysis.
- Author
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Deroo R, Trépo E, Holvoet T, De Pauw M, Geerts A, Verhelst X, Colle I, Van Vlierberghe H, Fallon MB, and Raevens S
- Subjects
- Case-Control Studies, Endothelin Receptor Antagonists pharmacology, Hemodynamics drug effects, Hemodynamics physiology, Humans, Hypertension, Portal complications, Hypertension, Portal mortality, Hypertension, Portal physiopathology, Hypertension, Pulmonary complications, Hypertension, Pulmonary mortality, Hypertension, Pulmonary physiopathology, Observational Studies as Topic, Prognosis, Randomized Controlled Trials as Topic, Survival Rate, Treatment Outcome, Vasodilator Agents pharmacology, Endothelin Receptor Antagonists therapeutic use, Hypertension, Portal therapy, Hypertension, Pulmonary therapy, Liver Transplantation statistics & numerical data, Vasodilator Agents therapeutic use
- Abstract
Background and Aims: Untreated portopulmonary hypertension (PoPH) carries a poor prognosis. Previous reports have described vasomodulator (VM) therapy and liver transplantation (LT) as treatment options. We aimed to provide summary estimates on the endpoints of pulmonary hemodynamics and survival in patients with PoPH, treated with different modalities., Approach and Results: We performed a systematic review with meta-analysis of mainly observational and case-control studies describing no treatment, VM, LT, or VM + LT in patients with PoPH. Twenty-six studies (1,019 patients) were included. Both VM and VM + LT improve pulmonary hemodynamics. A substantial proportion of patients treated with VM become eligible for LT (44%; 95% confidence interval [CI], 31-58). Pooled estimates for 1-, and 3-year postdiagnosis survival in patients treated with VM were 86% (95% CI, 81-90) and 69% (95% CI, 50-84) versus 82% (95% CI, 52-95) and 67% (95% CI, 53-78) in patients treated with VM + LT. Of note, studies reporting on the effect of VM mainly included Child-Pugh A/B patients, whereas studies reporting on VM + LT mainly included Child-Pugh B/C. Seven studies (238 patients) included both patients who received VM only and patients who received VM + LT. Risk of death in VM-only-treated patients was significantly higher than in patients who could be transplanted as well (odds ratio, 3.5; 95% CI, 1.4-8.8); however, importantly, patients who proceeded to transplant had been selected very strictly. In 50% of patients, VM can be discontinued post-LT (95% CI, 38-62)., Conclusions: VM and VM + LT both improve pulmonary hemodynamics and prognosis in PoPH. In a strictly selected subpopulation of cases where LT is indicated based on severe liver disease and where LT is considered safe and feasible, treatment with VM + LT confers a better prognosis. Considering successful VM, 44% can proceed to LT, with half being able to postoperatively stop medication., (© 2020 by the American Association for the Study of Liver Diseases.)
- Published
- 2020
- Full Text
- View/download PDF
43. Myeloid-specific IRE1alpha deletion reduces tumour development in a diabetic, non-alcoholic steatohepatitis-induced hepatocellular carcinoma mouse model.
- Author
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Van Campenhout S, Tilleman L, Lefere S, Vandierendonck A, Raevens S, Verhelst X, Geerts A, Van Nieuwerburgh F, Van Vlierberghe H, and Devisscher L
- Subjects
- Animals, Blood Glucose metabolism, Diet, Western, Glucose Intolerance prevention & control, Kupffer Cells pathology, Liver pathology, Liver Neoplasms genetics, Liver Neoplasms, Experimental genetics, Macrophages pathology, Mice, Mice, Knockout, Mice, Transgenic, Transcriptional Activation, Diabetes Mellitus, Experimental complications, Endoribonucleases genetics, Liver Neoplasms etiology, Liver Neoplasms prevention & control, Liver Neoplasms, Experimental etiology, Liver Neoplasms, Experimental prevention & control, Non-alcoholic Fatty Liver Disease complications, Protein Serine-Threonine Kinases genetics
- Abstract
Background and Aims: Obesity, diabetes and associated non-alcoholic steatohepatitis (NASH) are rising risk factors for hepatocellular carcinoma (HCC). Macrophages are important immune cells involved in inflammation and tumour development. Macrophage inositol-requiring enzyme 1 alpha (IRE1α), an ER-stress protein, has been shown to be involved in macrophage cytokine production, and myeloid-specific IRE1α knock-out (myeloid IRE1α-KO) mice showed reduced weight gain during high-fat diet feeding. However, the effect of myeloid IRE1α on NASH and subsequent HCC development has not been examined. Here, we characterized the transcriptional profile of the hepatic macrophage population in a diabetes-NASH-HCC mouse model, and investigated the effect of myeloid-specific IRE1α deletion on the phenotype of hepatic macrophage subsets and experimental NASH-HCC development., Methods: Mice with non-functional myeloid IRE1α were created by crossing Ire1a floxed mice with Lysm-Cre mice. Two-day old myeloid IRE1α-KO and wild type (WT) mice were subcutaneously injected with streptozotocin (STZ), and male mice were fed a high-fat, -sucrose, -cholesterol diet (Western diet, WD) from the age of 4 weeks until 21 weeks. Control myeloid IRE1α-KO and WT mice received a PBS injection and were fed a matched control diet. These mice were evaluated for obesity, diabetes, NASH and HCC. The hepatic macrophage population was evaluated by flow cytometry and RNA sequencing on FACS-isolated macrophage subsets., Results: STZ-injection and WD feeding resulted in an impaired glucose tolerance, advanced NASH with fibrosis, and HCC development. Myeloid IRE1α-KO STZ mice showed lower fasting glucose levels at the start of WD feeding, and an improved glucose tolerance and attenuated HCC development after 17 weeks of WD feeding despite a similar degree of liver steatosis and inflammation compared to WT mice. Transcriptomic analysis of WT liver Kupffer cells, macrophages and monocytes revealed phenotypical changes in those cell subsets during NASH-HCC development. Isolated liver Kupffer cells and macrophages from mice with a myeloid IRE1α deletion showed downregulated pathways involved in immune system activation and metabolic pathways (only in Kupffer cells), whereas pathways involved in cell division and metabolism were upregulated in monocytes. These transcriptional differences were attenuated during NASH-HCC development., Conclusion: Our results show that myeloid-specific IRE1α deletion results in an altered transcriptional profile of hepatic macrophages and dampens diabetes-induced NASH-HCC development, possibly by attenuated diabetes induction., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
44. PORTICO: First Randomized Controlled Trial of Vasomodulator Therapy in Portopulmonary Hypertension.
- Author
-
Raevens S and Fallon MB
- Subjects
- Double-Blind Method, Humans, Pyrimidines, Sulfonamides, Hypertension, Liver Diseases
- Published
- 2020
- Full Text
- View/download PDF
45. Combination of sivelestat and N-acetylcysteine alleviates the inflammatory response and exceeds standard treatment for acetaminophen-induced liver injury.
- Author
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Raevens S, Van Campenhout S, Debacker PJ, Lefere S, Verhelst X, Geerts A, Van Vlierberghe H, Colle I, and Devisscher L
- Subjects
- Analgesics, Non-Narcotic toxicity, Animals, Chemical and Drug Induced Liver Injury etiology, Chemical and Drug Induced Liver Injury pathology, Drug Therapy, Combination, Free Radical Scavengers pharmacology, Glycine pharmacology, Inflammation etiology, Inflammation pathology, Male, Mice, Mice, Inbred C57BL, Serine Proteinase Inhibitors pharmacology, Acetaminophen toxicity, Acetylcysteine pharmacology, Chemical and Drug Induced Liver Injury drug therapy, Glycine analogs & derivatives, Inflammation prevention & control, Sulfonamides pharmacology
- Abstract
Hepatocyte death during acetaminophen (APAP) intoxication elicits a reactive inflammatory response, with hepatic recruitment of neutrophils and monocytes, which further aggravates liver injury. Neutrophil elastase (NE), secreted by activated neutrophils, carries degradative and cytotoxic functions and maintains a proinflammatory state. We investigated NE as a therapeutic target in acetaminophen-induced liver injury (AILI). C57BL/6 mice were administered a toxic dose of APAP, 2 h prior to receiving the NE inhibitor sivelestat, N-acetylcysteine (NAC), or a combination therapy, and were euthanized after 24 and 48 h. Upon APAP overdose, neutrophils and monocytes infiltrate the injured liver, accompanied by increased levels of NE. Combination therapy of NAC and sivelestat significantly limits liver damage, as evidenced by lower serum transaminase levels and less hepatic necrosis compared to mice that received APAP only, and this to a greater extent than NAC monotherapy. Lower hepatic expression of proinflammatory markers was observed in the combination treatment group, and flow cytometry revealed significantly less monocyte influx in livers from mice treated with the combination therapy, compared to untreated mice and mice treated with NAC only. The potential of NE to induce leukocyte migration was confirmed in vitro. Importantly, sivelestat did not impair hepatic repair. In conclusion, combination of NE inhibition with sivelestat and NAC dampens the inflammatory response and reduces liver damage following APAP overdose. This strategy exceeds the standard of care and might represent a novel therapeutic option for AILI., (©2019 Society for Leukocyte Biology.)
- Published
- 2020
- Full Text
- View/download PDF
46. Angiopoietin-2 Promotes Pathological Angiogenesis and Is a Therapeutic Target in Murine Nonalcoholic Fatty Liver Disease.
- Author
-
Lefere S, Van de Velde F, Hoorens A, Raevens S, Van Campenhout S, Vandierendonck A, Neyt S, Vandeghinste B, Vanhove C, Debbaut C, Verhelst X, Van Dorpe J, Van Steenkiste C, Casteleyn C, Lapauw B, Van Vlierberghe H, Geerts A, and Devisscher L
- Subjects
- Adult, Angiopoietin-2 antagonists & inhibitors, Angiopoietin-2 blood, Animals, Disease Models, Animal, Female, Humans, Male, Mice, Middle Aged, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease drug therapy, Prospective Studies, Angiopoietin-2 physiology, Liver blood supply, Neovascularization, Pathologic drug therapy, Non-alcoholic Fatty Liver Disease etiology
- Abstract
Angiogenesis contributes to the development of nonalcoholic steatohepatitis (NASH) and promotes inflammation, fibrosis, and progression to hepatocellular carcinoma (HCC). Angiopoietin-2 (Ang-2) is a key regulator of angiogenesis. We aimed to investigate the role of Ang-2 and its potential as a therapeutic target in NASH using human samples, in vivo mouse models, and in vitro assays. Serum Ang-2 levels were determined in 104 obese patients undergoing bariatric surgery and concomitant liver biopsy. The effect of the Ang-2/Tie2 receptor inhibiting peptibody L1-10 was evaluated in the methionine-choline deficient (MCD) and streptozotocin-western diet nonalcoholic fatty liver disease mouse models, and in vitro on endothelial cells and bone marrow-derived macrophages. The hepatic vasculature was visualized with µCT scans and scanning electron microscopy of vascular casts. Serum Ang-2 levels were increased in patients with histological NASH compared with patients with simple steatosis and correlated with hepatic CD34 immunoreactivity as a marker of hepatic angiogenesis. Serum and hepatic Ang-2 levels were similarly increased in mice with steatohepatitis. Both preventive and therapeutic L1-10 treatment reduced hepatocyte ballooning and fibrosis in MCD diet-fed mice and was associated with reduced hepatic angiogenesis and normalization of the vascular micro-architecture. Liver-isolated endothelial cells and monocytes from MCD-fed L1-10-treated mice showed reduced expression of leukocyte adhesion and inflammatory markers, respectively, compared with cells from untreated MCD diet-fed mice. In the streptozotocin-western diet model, therapeutic Ang-2 inhibition was able to reverse NASH and attenuate HCC progression. In vitro, L1-10 treatment mitigated increased cytokine production in lipopolysaccharide-stimulated endothelial cells but not in macrophages. Conclusion: Our findings provide evidence for Ang-2 inhibition as a therapeutic strategy to target pathological angiogenesis in NASH., (© 2018 by the American Association for the Study of Liver Diseases.)
- Published
- 2019
- Full Text
- View/download PDF
47. Outcome of liver transplantation for hepatopulmonary syndrome: a Eurotransplant experience.
- Author
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Raevens S, Rogiers X, Geerts A, Verhelst X, Samuel U, van Rosmalen M, Berlakovich G, Delwaide J, Detry O, Lehner F, Mittler J, Nadalin S, Nevens F, Pirenne J, Saner F, Schneeberger S, Stippel D, Turk JM, Zoltan M, Troisi RI, Van Vlierberghe H, and Colle I
- Subjects
- End Stage Liver Disease surgery, Europe, Humans, Oxygen metabolism, Proportional Hazards Models, Registries, Retrospective Studies, Risk, Treatment Outcome, Hepatopulmonary Syndrome surgery, Liver Transplantation mortality
- Abstract
Competing Interests: Conflict of interest: S. Raevens has nothing to disclose. Conflict of interest: X. Rogiers has nothing to disclose. Conflict of interest: A. Geerts has nothing to disclose. Conflict of interest: X. Verhelst has nothing to disclose. Conflict of interest: U. Samuel has nothing to disclose. Conflict of interest: M. van Rosmalen has nothing to disclose. Conflict of interest: G. Berlakovich has nothing to disclose. Conflict of interest: J. Delwaide has nothing to disclose. Conflict of interest: O. Detry has nothing to disclose. Conflict of interest: F. Lehner has nothing to disclose. Conflict of interest: J. Mittler has nothing to disclose. Conflict of interest: S. Nadalin has nothing to disclose. Conflict of interest: F. Nevens reports receiving grants from Roche, Astellas and Sandoz, grants and consultancy fees from BMS, CAF, MSD, TwinPharma and Ipsen, and consultancy fees from Gilead, Novartis, Abbvie, Promethera Biosciences, Durect, Ferring, Gore, Cook Medical, Biotest and Intercept, outside the submitted work. Conflict of interest: J. Pirenne has nothing to disclose. Conflict of interest: F. Saner has nothing to disclose. Conflict of interest: S. Schneeberger reports being a member of an expert group and a consultant for Merck; being a member of an expert group and a speaker for Astellas; receiving grants, and being a member of an expert group and a consultant for Chiesi; being a member of an expert group, a speaker and a consultant for Teva; being a speaker for Novartis; and receiving grants from Sandoz, all outside the submitted work. Conflict of interest: D. Stippel has nothing to disclose. Conflict of interest: M. Turk Jerovšek has nothing to disclose. Conflict of interest: M. Zoltan has nothing to disclose. Conflict of interest: R.I. Troisi has nothing to disclose. Conflict of interest: H. Van Vlierberghe has nothing to disclose. Conflict of interest: I. Colle reports consultancy for Promethera outside the submitted work.
- Published
- 2019
- Full Text
- View/download PDF
48. Why Pulse Oximetry Is Inaccurate in Liver Cirrhosis: Ancient Knowledge.
- Author
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Raevens S, Colle I, Geerts A, and Van Vlierberghe H
- Subjects
- Humans, Liver Cirrhosis, Oximetry, Hepatopulmonary Syndrome, Liver Transplantation
- Published
- 2019
- Full Text
- View/download PDF
49. Potential Clinical Targets in Hepatopulmonary Syndrome: Lessons From Experimental Models.
- Author
-
Raevens S and Fallon MB
- Subjects
- Animals, Disease Models, Animal, Endothelial Cells pathology, Hepatopulmonary Syndrome drug therapy, Humans, Mice, Monocytes pathology, Neovascularization, Pathologic physiopathology, Rats, Hepatopulmonary Syndrome physiopathology, Liver physiopathology, Lung physiopathology
- Abstract
Hepatopulmonary syndrome (HPS) is a relatively common and potentially severe pulmonary complication of cirrhosis with increased risk of mortality. In experimental models, a complex interaction between pulmonary endothelial cells, monocytes, and the respiratory epithelium, which produces chemokines, cytokines, and angiogenic growth factors, causes alterations in the alveolar microvasculature, resulting in impaired oxygenation. Model systems are critical for evaluating mechanisms and for preclinical testing in HPS, due to the challenges of evaluating the lung in the setting of advanced liver disease in humans. This review provides an overview of current knowledge and recent findings in the rodent common bile duct ligation model of HPS, which recapitulates many features of human disease. We focus on the concepts of endothelial derangement, monocyte infiltration, angiogenesis, and alveolar type II cell dysfunction as main contributors and potential targets for therapy., (© 2018 by the American Association for the Study of Liver Diseases.)
- Published
- 2018
- Full Text
- View/download PDF
50. Placental growth factor inhibition targets pulmonary angiogenesis and represents a therapy for hepatopulmonary syndrome in mice.
- Author
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Raevens S, Geerts A, Paridaens A, Lefere S, Verhelst X, Hoorens A, Van Dorpe J, Maes T, Bracke KR, Casteleyn C, Jonckx B, Horvatits T, Fuhrmann V, Van Vlierberghe H, Van Steenkiste C, Devisscher L, and Colle I
- Subjects
- Animals, Antibodies, Monoclonal pharmacology, Biomarkers metabolism, Common Bile Duct surgery, Disease Models, Animal, Endoglin blood, Hepatopulmonary Syndrome physiopathology, Humans, Ligation methods, Liver pathology, Liver Cirrhosis pathology, Male, Mice, Placenta Growth Factor antagonists & inhibitors, Hepatopulmonary Syndrome metabolism, Lung pathology, Neovascularization, Pathologic metabolism, Placenta Growth Factor metabolism
- Abstract
Hepatopulmonary syndrome (HPS) is a severe complication of cirrhosis with increased risk of mortality. Pulmonary microvascular alterations are key features of HPS; but underlying mechanisms are incompletely understood, and studies on HPS are limited to rats. Placental growth factor (PlGF), a proangiogenic molecule that is selectively involved in pathological angiogenesis, may play an important role in HPS development; however, its role has never been investigated. In this study, we validated an HPS model by common bile duct ligation (CBDL) in mice, investigated the kinetic changes in pulmonary angiogenesis and inflammation during HPS development, and provide evidence for a novel therapeutic strategy by targeting pathological angiogenesis. Mice with CBDL developed hypoxemia and intrapulmonary shunting on a background of liver fibrosis. Pulmonary alterations included increased levels of proangiogenic and inflammatory markers, which was confirmed in serum of human HPS patients. Increased PlGF production in HPS mice originated from alveolar type II cells and lung macrophages, as demonstrated by immunofluorescent staining. Dysfunctional vessel formation in CBDL mice was visualized by microscopy on vascular corrosion casts. Both prophylactic and therapeutic anti-PlGF (αPlGF) antibody treatment impeded HPS development, as demonstrated by significantly less intrapulmonary shunting and improved gas exchange. αPlGF treatment decreased endothelial cell dysfunction in vivo and in vitro and was accompanied by reduced pulmonary inflammation. Importantly, αPlGF therapy did not affect liver alterations, supporting αPlGF's ability to directly target the pulmonary compartment., Conclusion: CBDL in mice induces HPS, which is mediated by PlGF production; αPlGF treatment improves experimental HPS by counteracting pulmonary angiogenesis and might be an attractive therapeutic strategy for human HPS. (Hepatology 2017)., (© 2017 by the American Association for the Study of Liver Diseases.)
- Published
- 2018
- Full Text
- View/download PDF
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