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2. FRI-074-YI Rifaximin reduces healthcare utilization but not overall costs in patients with cirrhosis and recurrent episodes of hepatic encephalopathy: a retrospective efficacy study

Author

van Doorn, Diederick, primary, van Eekhout, Kirsi, additional, de Wit, Koos, additional, Baak, L.C., additional, Klemt-Kropp, Michael, additional, Verwer, Bart, additional, Friederich, Philip W., additional, de Bruin, Gijs J., additional, Vos, Xander, additional, and Bart Takkenberg, R., additional

Published
2024
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3. Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial

Author

Pose, Elisa, Napoleone, Laura, Amin, Ahmed, Campion, Daniela, Jimenez, César, Piano, Salvatore, Roux, Olivier, Uschner, Frank Erhard, de Wit, Koos, Zaccherini, Giacomo, Alessandria, Carlo, Angeli, Paolo, Bernardi, Mauro, Beuers, Ulrich, Caraceni, Paolo, Durand, François, Mookerjee, Rajeshwar P, Trebicka, Jonel, Vargas, Victor, Andrade, Raúl J, Carol, Marta, Pich, Judit, Ferrero, Juan, Domenech, Gema, Llopis, Marta, Torres, Ferran, Kamath, Patrick S, Abraldes, Juan G, Solà, Elsa, and Ginès, Pere

Published
2020
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4. Simvastatin plus Rifaximin to prevent ACLF in patients with decompensated cirrhosis. A randomised, double-blind, placebo-controlled, phase-3 trial: the liverhope efficacy trial

Author

Pose, Elisa, primary, Jiménez, César, additional, Zaccherini, Giacomo, additional, Campion, Daniela, additional, Piano, Salvatore, additional, Uschner, Frank Erhard, additional, de Wit, Koos, additional, Roux, Olivier, additional, Gananandan, Kohilan, additional, Laleman, Wim, additional, Solé, Cristina, additional, Alonso, Sonia, additional, Cuyas, Berta, additional, Ariza, Xavier, additional, Juanola, Adria, additional, Ma, Ann T, additional, Napoleone, Laura, additional, Gratacos, Jordi, additional, Tonon, Marta, additional, Pompili, Enrico, additional, Sánchez-Delgado, Jordi, additional, Carol, Marta, additional, Perez, Martina, additional, Fabrellas, Núria, additional, Pich, Judit, additional, Martell, Claudia, additional, Casanovas, Georgina, additional, Domenech, Gemma, additional, Torres, Ferran, additional, Manuel, Víctor, additional, Blasco, Vargas, additional, Caraceni, Paolo, additional, Alessandria, Carlo, additional, Angeli, Paolo, additional, Trebicka, Jonel, additional, Beuers, Ulrich, additional, Francoz, Claire, additional, Mookerjee, Raj, additional, Bañares, Rafael, additional, Soriano, German, additional, Hernaez, Ruben, additional, Allegretti, Andrew S., additional, Morales-Ruiz, Manuel, additional, Serra, Miquel, additional, Watson, Hugh, additional, Abraldes, Juan G, additional, Kamath, Patrick S., additional, and Ginès, Pere, additional

Published
2023
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6. Issue Cover

Author

de Wit, Koos, primary, Beuers, Ulrich, additional, Mukha, Anna, additional, Stigter, Edwin C. A., additional, Gulersonmez, M. Can, additional, Ramos Pittol, Jose M., additional, Middendorp, Sabine, additional, Takkenberg, R. Bart, additional, and van Mil, Saskia W. C., additional

Published
2023
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8. Rifaximin stimulates nitrogen detoxification by PXR-independent mechanisms in human small intestinal organoids

Author

CMM Groep Van Mil, Cancer, CMM Groep Burgering, Child Health, Regenerative Medicine and Stem Cells, CMM, de Wit, Koos, Beuers, Ulrich, Mukha, Anna, Stigter, Edwin, Gulersonmez, M Can, Ramos Pittol, Jose M, Middendorp, Sabine, Takkenberg, R Bart, van Mil, Saskia W C, CMM Groep Van Mil, Cancer, CMM Groep Burgering, Child Health, Regenerative Medicine and Stem Cells, CMM, de Wit, Koos, Beuers, Ulrich, Mukha, Anna, Stigter, Edwin, Gulersonmez, M Can, Ramos Pittol, Jose M, Middendorp, Sabine, Takkenberg, R Bart, and van Mil, Saskia W C

Published
2023

9. Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis

Author

Juanola, Adrià, Ma, Ann Thu, de Wit, Koos, Gananandan, Kohilan, Roux, Olivier, Zaccherini, Giacomo, Jiménez, César, Tonon, Marta, Solé, Cristina, Villaseca, Clara, Uschner, Frank E, Graupera, Isabel, Pose, Elisa, Moreta, Maria José, Campion, Daniela, Beuers, Ulrich, Mookerjee, Rajeshawar P, Francoz, Claire, Durand, Francois, Vargas, Victor, Piano, Salvatore, Alonso, Sonia, Trebicka, Jonel, Laleman, Wim, Asrani, Sumeet K, Soriano, German, Alessandria, Carlo, Serra-Burriel, Miquel, Morales-Ruiz, Manuel, Torres, Ferran, Allegretti, Andrew S, Krag, Aleksander, Caraceni, Paolo, Watson, Hugh, Abraldes, Juan G, Solà, Elsa, Kamath, Patrick S, Hernaez, Ruben, and Ginès, Pere

Abstract

BackgroundPatients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications.MethodsWe performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not.ResultsOf 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46).ConclusionNovel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.

Published
2024
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13. Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis

Author

Pose, Elisa, primary, Solà, Elsa, additional, Lozano, Juan J., additional, Juanola, Adrià, additional, Sidorova, Julia, additional, Zaccherini, Giacomo, additional, de Wit, Koos, additional, Uschner, Frank, additional, Tonon, Marta, additional, Kazankov, Konstantin, additional, Jiménez, Cesar, additional, Campion, Daniela, additional, Napoleone, Laura, additional, Ma, Ann T., additional, Carol, Marta, additional, Morales-Ruiz, Manuel, additional, Alessandria, Carlo, additional, Beuers, Ulrich, additional, Caraceni, Paolo, additional, Francoz, Claire, additional, Durand, François, additional, Mookerjee, Rajeshwar P., additional, Trebicka, Jonel, additional, Vargas, Victor, additional, Piano, Salvatore, additional, Watson, Hugh, additional, Abraldes, Juan G., additional, Kamath, Patrick S., additional, Davis, Mark M., additional, Ginès, Pere, additional, Schulz, M., additional, Ferstl, P., additional, Giovo, I., additional, Roux, O., additional, Simon-Talero, M., additional, Pérez-Guasch, M., additional, Rubio, A. B., additional, Cervera, M., additional, Martínez, S., additional, Fabrellas, N., additional, Pich, J., additional, Vives, A., additional, Avitabile, E., additional, Graupera, I., additional, Solé, C., additional, Bassegoda, O., additional, Gratacós-Ginès, J., additional, Joyera, M., additional, Palacio, E., additional, Aban, M., additional, Lanzillotti, T., additional, Nicolao, G., additional, Chiappa, M. T., additional, Esnault, V., additional, Andrade, R., additional, Pavesi, M., additional, Korenjak, M., additional, Farrés, J., additional, Serra-Burriel, M., additional, and Angeli, P., additional

Published
2022
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14. Rifaximin stimulates nitrogen detoxification by PXR‐independent mechanisms in human small intestinal organoids.

Author

de Wit, Koos, Beuers, Ulrich, Mukha, Anna, Stigter, Edwin C. A., Gulersonmez, M. Can, Ramos Pittol, Jose M., Middendorp, Sabine, Takkenberg, R. Bart, and van Mil, Saskia W. C.

Subjects
*RIFAXIMIN, *PREGNANE X receptor, *AMINO acid metabolism, *HEPATIC encephalopathy, *ORGANOIDS
Abstract

Background and Aims: Recurrent hepatic encephalopathy (HE) is characterized by hyperammonaemia in combination with neuropsychiatric abnormalities and is treated with lactulose and rifaximin. Rifaximin is a pregnane X receptor (PXR) agonist with low systemic and high intestinal bioavailability. The mechanisms by which it alleviates HE are unclear. We used human small intestinal (hSI) organoids to study whether rifaximin, via PXR activation, affects the epithelial biotransformation machinery, and to gain understanding of its low systemic availability. Methods: We generated PXR knockdown hSI organoids via lentiviral delivery of short hairpin RNAs. Organoids were cultured for 24 h with rifaximin or rifampicin. RNA‐sequencing and metabolomics were performed to analyse gene expression and amino acid metabolism. Luminal rifaximin was quantified by photospectrometry. Results: Treatment of wild‐type hSI organoids with rifaximin resulted in >twofold differential expression of 131 genes compared to DMSO. These effects were largely PXR independent and related to amino acid metabolism. Rifaximin decreased expression of glutaminase‐2 and increased expression of asparagine synthetase and solute carrier 7A11, thereby increasing intracellular glutamine and asparagine concentrations, indicating active ammonia detoxification. Rifaximin was apically excreted into the lumen in an ATP binding cassette B1 (ABCB1)‐dependent manner. Conclusions: Rifaximin—after uptake into enterocytes—stimulates intracellular nitrogen detoxification by PXR‐independent mechanisms. Active apical excretion of rifaximin by ABCB1 into the intestinal lumen explains its low systemic bioavailability. Our study implies that rifaximin, next to modulation of the microbiome, has direct effects on ammonia scavenging in the human small intestinal epithelium. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis

Author

Pose, Elisa, Solà, Elsa, Lozano, Juan J., Juanola, Adrià, Sidorova, Julia, Zaccherini, Giacomo, Wit, Koos, Uschner, Frank, Tonon, Marta, Kazankov, Konstantin, Jiménez, Cesar, Campion, Daniela, Napoleone, Laura, Ma, Ann T., Carol, Marta, Morales‐Ruiz, Manuel, Alessandria, Carlo, Beuers, Ulrich, Caraceni, Paolo, Francoz, Claire, Durand, François, Mookerjee, Rajeshwar P., Trebicka, Jonel, Vargas, Victor, Piano, Salvatore, Watson, Hugh, Abraldes, Juan G., Kamath, Patrick S., Davis, Mark M., Ginès, Pere, Schulz, M., Ferstl, P., Giovo, I., Roux, O., Simon‐Talero, M., Pérez‐Guasch, M., Rubio, A.B., Cervera, M., Martínez, S., Fabrellas, N., Pich, J., Vives, A., Avitabile, E., Graupera, I., Solé, C., Bassegoda, O., Gratacós‐Ginès, J., Joyera, M., Palacio, E., Aban, M., Lanzillotti, T., Nicolao, G., Chiappa, M.T., Esnault, V., Andrade, R., Pavesi, M., Korenjak, M., Farrés, J., Serra‐Burriel, M., Angeli, P., Pose E., Sola E., Lozano J.J., Juanola A., Sidorova J., Zaccherini G., de Wit K., Uschner F., Tonon M., Kazankov K., Jimenez C., Campion D., Napoleone L., Ma A.T., Carol M., Morales-Ruiz M., Alessandria C., Beuers U., Caraceni P., Francoz C., Durand F., Mookerjee R.P., Trebicka J., Vargas V., Piano S., Watson H., Abraldes J.G., Kamath P.S., Davis M.M., Gines P., Schulz M., Ferstl P., Giovo I., Roux O., Simon-Talero M., Perez-Guasch M., Rubio A.B., Cervera M., Martinez S., Fabrellas N., Pich J., Vives A., Avitabile E., Graupera I., Sole C., Bassegoda O., Gratacos-Gines J., Joyera M., Palacio E., Aban M., Lanzillotti T., Nicolao G., Chiappa M.T., Esnault V., Andrade R., Pavesi M., Korenjak M., Farres J., Serra-Burriel M., Angeli P., Gastroenterology and Hepatology, Graduate School, Tytgat Institute for Liver and Intestinal Research, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Liver Cirrhosis, 0303 health sciences, Simvastatin, Hepatology, Kynurenine/therapeutic use, Tryptophan, Acute-On-Chronic Liver Failure, Tryptophan/therapeutic use, Rifaximin, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, simvastatin and rifaximin, Simvastatin/therapeutic use, Carnitine, Humans, Metabolomics, 030211 gastroenterology & hepatology, Carnitine/therapeutic use, Rifaximin/therapeutic use, Kynurenine, 030304 developmental biology, Liver Cirrhosis/drug therapy
Abstract

Patients with decompensated cirrhosis, particularly those with acute-on-chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE-SAFETY randomized, double-blind, placebo-controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography-tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan-kynurenine and carnitine beta-oxidation pathways. An ACLF-specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan-kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

Published
2021

16. The Use of Rifaximin in Patients With Cirrhosis

Author

Caraceni, Paolo, Vargas, Victor, Solà, Elsa, Alessandria, Carlo, de Wit, Koos, Trebicka, Jonel, Angeli, Paolo, Mookerjee, Rajeshwar P., Durand, François, Pose, Elisa, Krag, Aleksander, Bajaj, Jasmohan S., Beuers, Ulrich, Ginès, Pere, Universitat Autònoma de Barcelona, Caraceni, Paolo, Vargas, Victor, Solà, Elsa, Alessandria, Carlo, de Wit, Koos, Trebicka, Jonel, Angeli, Paolo, Mookerjee, Rajeshwar P., Durand, François, Pose, Elisa, Krag, Aleksander, Bajaj, Jasmohan S., Beuers, Ulrich, Ginès, Pere, and Universitat Autònoma de Barcelona

Abstract

Rifaximin is an oral nonsystemic antibiotic with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both gram-positive and gram-negative organisms. Rifaximin is currently used worldwide in patients with cirrhosis for preventing recurrent HE because its efficacy and safety have been proven by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which in turn can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted because evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas in the second part, its clinical effects are critically discussed. It clearly emerges that, because of its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than HE deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure, and mortality, are therefore eagerly awaited

Published
2021

17. LBO-01 - Simvastatin plus Rifaximin to prevent ACLF in patients with decompensated cirrhosis. A randomised, double-blind, placebo-controlled, phase-3 trial: the liverhope efficacy trial

Author

Pose, Elisa, Jiménez, César, Zaccherini, Giacomo, Campion, Daniela, Piano, Salvatore, Uschner, Frank Erhard, de Wit, Koos, Roux, Olivier, Gananandan, Kohilan, Laleman, Wim, Solé, Cristina, Alonso, Sonia, Cuyas, Berta, Ariza, Xavier, Juanola, Adria, Ma, Ann T, Napoleone, Laura, Gratacos, Jordi, Tonon, Marta, Pompili, Enrico, Sánchez-Delgado, Jordi, Carol, Marta, Perez, Martina, Fabrellas, Núria, Pich, Judit, Martell, Claudia, Casanovas, Georgina, Domenech, Gemma, Torres, Ferran, Manuel, Víctor, Blasco, Vargas, Caraceni, Paolo, Alessandria, Carlo, Angeli, Paolo, Trebicka, Jonel, Beuers, Ulrich, Francoz, Claire, Mookerjee, Raj, Bañares, Rafael, Soriano, German, Hernaez, Ruben, Allegretti, Andrew S., Morales-Ruiz, Manuel, Serra, Miquel, Watson, Hugh, Abraldes, Juan G, Kamath, Patrick S., and Ginès, Pere

Published
2023
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18. Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium

Author

LiverHope Consortium Investigators, Solà, Elsa, Pose Mendez, Elisa, Campion, Daniela, Piano, Salvatore, Roux, Olivier, Simon-Talero, Macarena, Uschner, Frank Erhard, Wit, Koos de, Zaccherini, Giacomo, Alessandria, Carlo, Beuers, Ulrich, Caraceni, Paolo, Francoz, Claire, Mookerjee, Rajeshwar Prosad, Trebicka, Jonel, Vargas Blasco, Victor Manuel, Serra, Miquel, Torres, Ferran, Montagnese, Sara, Krag, Aleksander, Hernaez, Ruben, Korenjak, Marko, Watson, Hugh, Abraldes, Juan G., Kamath, Patrick S., Ginès, Pere, LiverHope Consortium Investigators, Solà, Elsa, Pose Mendez, Elisa, Campion, Daniela, Piano, Salvatore, Roux, Olivier, Simon-Talero, Macarena, Uschner, Frank Erhard, Wit, Koos de, Zaccherini, Giacomo, Alessandria, Carlo, Beuers, Ulrich, Caraceni, Paolo, Francoz, Claire, Mookerjee, Rajeshwar Prosad, Trebicka, Jonel, Vargas Blasco, Victor Manuel, Serra, Miquel, Torres, Ferran, Montagnese, Sara, Krag, Aleksander, Hernaez, Ruben, Korenjak, Marko, Watson, Hugh, Abraldes, Juan G., Kamath, Patrick S., and Ginès, Pere

Abstract

Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.

Published
2020

19. Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium

Author

Solà, Elsa, primary, Pose, Elisa, additional, Campion, Daniela, additional, Piano, Salvatore, additional, Roux, Olivier, additional, Simon-Talero, Macarena, additional, Uschner, Frank, additional, de Wit, Koos, additional, Zaccherini, Giacomo, additional, Alessandria, Carlo, additional, Beuers, Ulrich, additional, Caraceni, Paolo, additional, Francoz, Claire, additional, Mookerjee, Rajeshwar P., additional, Trebicka, Jonel, additional, Vargas, Victor, additional, Serra, Miquel, additional, Torres, Ferran, additional, Montagnese, Sara, additional, Krag, Aleksander, additional, Hernaez, Ruben, additional, Korenjak, Marko, additional, Watson, Hugh, additional, Abraldes, Juan G., additional, Kamath, Patrick S., additional, Ginès, Pere, additional, Durand, F., additional, Bernardi, M., additional, Solé, C., additional, Pich, J., additional, Graupera, I., additional, Napoleone, L., additional, Jiménez, C., additional, Juanola, A., additional, Avitabile, E., additional, Ma, A., additional, Fabrellas, N., additional, Carol, M., additional, Palacio, E., additional, Aban, M., additional, Lanzillotti, T., additional, Nicolao, G., additional, Chiappa, M.T., additional, Esnault, V., additional, Forner, A., additional, Graf-Dirmeier, S., additional, Helder, J., additional, Lopez, M., additional, Cervera, M., additional, and Pérez-Guasch, M., additional

Published
2021
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22. Variable efficacy of TIPSS in the management of ectopic variceal bleeding: a multicentre retrospective study

Author

Oey, R.C. (Rosalie), K. de Wit (Koos), Moelker, A. (Adriaan), T. Atalik (Tugce), Delden, O.M. (Otto) van, Maleux, G. (Geert), Erler, N.S. (Nicole), Takkenberg, R.B. (R. Bart), Man, R.A. (Robert) de, Nevens, F. (Frederik), Buuren, H.R. (Henk) van, Oey, R.C. (Rosalie), K. de Wit (Koos), Moelker, A. (Adriaan), T. Atalik (Tugce), Delden, O.M. (Otto) van, Maleux, G. (Geert), Erler, N.S. (Nicole), Takkenberg, R.B. (R. Bart), Man, R.A. (Robert) de, Nevens, F. (Frederik), and Buuren, H.R. (Henk) van

Abstract

Background: Evidence for the efficacy of TIPSS in ectopic variceal bleeding (EctVB) is largely based on relatively small series. Aim: To define the efficacy of TIPSS in EctVB. Methods: Retrospective analysis of consecutive patients with chronic liver disease who presented with EctVB and received TIPSS in three tertiary centres in 1992-2016. Results: The study included 53 patients (70% male, median age 61 years, median model for end-stage liver disease (MELD) score 11). The ectopic varices were located around the insertion of stomas (40%), duodenum (23%), rectum (17%) and at other sites (20%). Three-quarters of the patients had previously received unsuccessful medical, endoscopic or surgical therapy. The median follow-up was 14.0 months. Following TIPSS, bleeding recurred in 12 patients: 6 of 12 (50%) with duodenal varices, 2 of 9 (22%) with rectal varices and one each with stomal (1/21), intraperitoneal (1/3), hepaticojejunostomy (1/2) and ascending colon varices (1/2). The risk factors for re-bleeding were MELD score at TIPSS placement (HR: 1.081 per point; 95% confidence interval (CI): 1.012-1.153; P = 0.034), varices located at site other than an enterostomy (HR: 9.770; 95%CI

Published
2018
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26. Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

Author

Juanola A, Ma AT, de Wit K, Gananandan K, Roux O, Zaccherini G, Jiménez C, Tonon M, Solé C, Villaseca C, Uschner FE, Graupera I, Pose E, Moreta MJ, Campion D, Beuers U, Mookerjee RP, Francoz C, Durand F, Vargas V, Piano S, Alonso S, Trebicka J, Laleman W, Asrani SK, Soriano G, Alessandria C, Serra-Burriel M, Morales-Ruiz M, Torres F, Allegretti AS, Krag A, Caraceni P, Watson H, Abraldes JG, Solà E, Kamath PS, Hernaez R, and Ginès P

Subjects
Humans, Prognosis, Prospective Studies, Interleukin-6, Severity of Illness Index, Biomarkers, Liver Cirrhosis complications, End Stage Liver Disease
Abstract

Background: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications., Methods: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not., Results: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46)., Conclusion: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone., Competing Interests: Competing interests: FD consults for Biotest. VV consults for Promethera and is on the speakers bureau for Intercept. SP advises Mallinckrodt. HW is employed by Evotec and owns stock in Sanofi. PG consults for and received grants from Gilead, Grifols and Mallinckrodt, and consults for Novartis, Martin and Ferring. JT has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit and CSL Behring. RH is part of the Editorial Board of the Gut journal., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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27. The Use of Rifaximin in Patients With Cirrhosis.

Author

Caraceni P, Vargas V, Solà E, Alessandria C, de Wit K, Trebicka J, Angeli P, Mookerjee RP, Durand F, Pose E, Krag A, Bajaj JS, Beuers U, and Ginès P

Subjects
Bacterial Infections prevention & control, Clinical Trials as Topic, Esophageal and Gastric Varices physiopathology, Esophageal and Gastric Varices prevention & control, Gastrointestinal Hemorrhage physiopathology, Gastrointestinal Hemorrhage prevention & control, Gastrointestinal Microbiome physiology, Hepatic Encephalopathy drug therapy, Hepatic Encephalopathy metabolism, Hepatic Encephalopathy physiopathology, Hepatorenal Syndrome metabolism, Hepatorenal Syndrome physiopathology, Hepatorenal Syndrome prevention & control, Humans, Hypertension, Portal metabolism, Hypertension, Portal physiopathology, Inflammation, Liver Cirrhosis metabolism, Liver Cirrhosis physiopathology, Peritonitis prevention & control, Anti-Bacterial Agents therapeutic use, Hepatic Encephalopathy prevention & control, Hypertension, Portal drug therapy, Liver Cirrhosis drug therapy, Rifaximin therapeutic use
Abstract

Rifaximin is an oral nonsystemic antibiotic with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both gram-positive and gram-negative organisms. Rifaximin is currently used worldwide in patients with cirrhosis for preventing recurrent HE because its efficacy and safety have been proven by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which in turn can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted because evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas in the second part, its clinical effects are critically discussed. It clearly emerges that, because of its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than HE deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure, and mortality, are therefore eagerly awaited., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Published
2021
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