المؤلفون: Katharina Burger, Finn Jung, Katharina Staufer, Ruth Ladurner, Michael Trauner, Anja Baumann, Annette Brandt, Ina Bergheim

المصدر: Redox Biology, Vol 71, Iss , Pp 103121- (2024)

مصطلحات موضوعية: Alcohol dehydrogenase, Alcohol metabolism, c-Jun N-terminal kinase, Tumor necrosis factor alpha, Steatotic liver disease, Medicine (General), R5-920, Biology (General), QH301-705.5

الوصف: Elevated fasting ethanol levels in peripheral blood frequently found in metabolic dysfunction-associated steatohepatitis (MASLD) patients even in the absence of alcohol consumption are discussed to contribute to disease development. To test the hypothesis that besides an enhanced gastrointestinal synthesis a diminished alcohol elimination through alcohol dehydrogenase (ADH) may also be critical herein, we determined fasting ethanol levels and ADH activity in livers and blood of MASLD patients and in wild-type ± anti-TNFα antibody (infliximab) treated and TNFα-/- mice fed a MASLD-inducing diet. Blood ethanol levels were significantly higher in patients and wild-type mice with MASLD while relative ADH activity in blood and liver tissue was significantly lower compared to controls. Both alterations were significantly attenuated in MASLD diet-fed TNFα-/- mice and wild-type mice treated with infliximab. Moreover, alcohol elimination was significantly impaired in mice with MASLD. In in vitro models, TNFα but not IL-1β or IL-6 significantly decreased ADH activity. Our data suggest that elevated ethanol levels in MASLD patients are related to TNFα-dependent impairments of ADH activity.

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S2213231724000971; https://doaj.org/toc/2213-2317

URL الوصول: https://doaj.org/article/619b7b66ac9c46d19ef8f721e4e42537

المؤلفون: Katharina Staufer, Heidemarie Huber, Jasmin Zessner-Spitzenberg, Rudolf Stauber, Armin Finkenstedt, Heike Bantel, Thomas S. Weiss, Markus Huber, Patrick Starlinger, Thomas Gruenberger, Thomas Reiberger, Susanne Sebens, Gail McIntyre, Ray Tabibiazar, Amato Giaccia, Heinz Zoller, Michael Trauner, Wolfgang Mikulits

المصدر: Cell Death Discovery, Vol 9, Iss 1, Pp 1-8 (2023)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671

الوصف: Abstract The expression of the receptor tyrosine kinase Axl and its cleavage product soluble Axl (sAxl) is increased in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this multicenter study, we evaluated the diagnostic value of Gas6, the high-affinity ligand of Axl, in patients with chronic liver disease. Levels of sAxl and Gas6, and their albumin (alb) ratios were analyzed in serum samples of patients with biopsy-proven liver fibrosis, end-stage liver disease, HCC, and healthy controls, and were compared to Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF™) test, Child-Pugh score (CPS), model of end-stage liver disease (MELD) score, hepatic venous pressure gradient, and α-fetoprotein, respectively. A total of 1111 patients (median age 57.8 y, 67.3% male) was analyzed. Gas6/alb showed high diagnostic accuracy for the detection of significant (≥F2: AUC 0.805) to advanced fibrosis (≥F3: AUC 0.818), and was superior to Fib-4 for the detection of cirrhosis (F4: AUC 0.897 vs. 0.878). In addition, Gas6/alb was highly predictive of liver disease severity (Odds ratios for CPS B/C, MELD ≥ 15, and clinically significant portal hypertension (CSPH) were 16.534, 10.258, and 12.115), and was associated with transplant-free survival (Hazard ratio 1.031). Although Gas6 and Gas6/alb showed high diagnostic accuracy for the detection of HCC in comparison to chronic liver disease patients without cirrhosis (AUC 0.852, 0.868), they failed to discriminate between HCC in cirrhosis versus cirrhosis only. In conclusion, Gas6/alb shows a high accuracy to detect significant to advanced fibrosis and cirrhosis, and predicts severity of liver disease including CSPH.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2058-7716

URL الوصول: https://doaj.org/article/6ec11fb752674d009f3b4dccfb87f223

المؤلفون: Olivier de Rougemont, Yun Deng, Lukas Frischknecht, Caroline Wehmeier, Jean Villard, Sylvie Ferrari-Lacraz, Déla Golshayan, Monique Gannagé, Isabelle Binet, Urs Wirthmueller, Daniel Sidler, Thomas Schachtner, Stefan Schaub, Jakob Nilsson, the Swiss Transplant Cohort Study, Patrizia Amico, Andres Axel, John David Aubert, Vanessa Banz, Beckmann Sonja, Guido Beldi, Christoph Berger, Ekaterine Berishvili, Pierre-Yves Bochud, Sanda Branca, Heiner Bucher, Thierry Carrel, Emmanuelle Catana, Yves Chalandon, Sabina De Geest, Olivier De Rougemont, Michael Dickenmann, Joëlle Lynn Dreifuss, Michel Duchosal, Thomas Fehr, Nicola Franscini, Christian Garzoni, Paola Gasche Soccal, Christophe Gaudet, Nicolas Goossens, Karine Hadaya, Jörg Halter, Dominik Heim, Christoph Hess, Sven Hillinger, Hans Hirsch, Patricia Hirt, Günther Hofbauer, Uyen Huynh-Do, Franz Immer, Michael Koller, Mirjam Laager, Bettina Laesser, Roger Lehmann, Alexander Leichtle, Christian Lovis, Oriol Manuel, Hans-Peter Marti, Pierre Yves Martin, Michele Martinelli, Valérie McLin, Katell Mellac, Aurelia Mercay, Karin Mettler, Nicolas Mueller, Antonia Müller, Thomas Müller, Ulrike Müller-Arndt, Beat Müllhaupt, Mirjam Nägeli, Graziano Oldani, Manuel Pascual, Klara Posfay-Barbe, Juliane Rick, Anne Rosselet, Simona Rossi, Silvia Rothlin, Frank Ruschitzka, Urs Schanz, Aurelia Schnyder, Macé Schuurmans, Thierry Sengstag, Federico Simonetta, Katharina Staufer, Susanne Stampf, Jürg Steiger, Guido Stirniman, Ueli Stürzinger, Christian Van Delden, Jean-Pierre Venetz, Julien Vionnet, Madeleine Wick, Markus Wilhlem, Patrick Yerly

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: kidney transplantation, donor specific antibodies, ABMR, graft loss, virtual cross-match, living donation, Immunologic diseases. Allergy, RC581-607

الوصف: IntroductionThe type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome.MethodsWe investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants.ResultsThere was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (

وصف الملف: electronic resource

Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1104371/full; https://doaj.org/toc/1664-3224

URL الوصول: https://doaj.org/article/4477ab4529c049ca9d56bbf4349cc853

المؤلفون: Katharina Staufer, Rudolf E. Stauber

المصدر: Biomedicines, Vol 11, Iss 8, p 2108 (2023)

مصطلحات موضوعية: non-alcoholic fatty liver disease (NAFLD), metabolic-dysfunction associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), alcohol-related liver disease (ALD), steatotic liver disease (SLD), Biology (General), QH301-705.5

الوصف: Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), both of them accounting for fatty liver disease (FLD), are among the most common chronic liver diseases globally, contributing to substantial public health burden. Both NAFLD and ALD share a similar picture of clinical presentation yet may have differences in prognosis and treatment, which renders early and accurate diagnosis difficult but necessary. While NAFLD is the fastest increasing chronic liver disease, the prevalence of ALD has seemingly remained stable in recent years. Lately, the term steatotic liver disease (SLD) has been introduced, replacing FLD to reduce stigma. SLD represents an overarching term to primarily comprise metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as alcohol-related liver disease (ALD), and MetALD, defined as a continuum across which the contribution of MASLD and ALD varies. The present review discusses current knowledge on common denominators of NAFLD/MASLD and ALD in order to highlight clinical and research needs to improve our understanding of SLD.

وصف الملف: electronic resource

Relation: https://www.mdpi.com/2227-9059/11/8/2108; https://doaj.org/toc/2227-9059

URL الوصول: https://doaj.org/article/7a33fdc20f474038b507069d0a92bb0b

المؤلفون: Lukas Frischknecht, Yun Deng, Caroline Wehmeier, Olivier de Rougemont, Jean Villard, Sylvie Ferrari-Lacraz, Déla Golshayan, Monique Gannagé, Isabelle Binet, Urs Wirthmueller, Daniel Sidler, Thomas Schachtner, Stefan Schaub, Jakob Nilsson, the Swiss Transplant Cohort Study, Patrizia Amico, Andres Axel, John David Aubert, Vanessa Banz, Beckmann Sonja, Guido Beldi, Christoph Berger, Ekaterine Berishvili, Pierre-Yves Bochud, Sanda Branca, Heiner Bucher, Thierry Carrel, Emmanuelle Catana, Yves Chalandon, Sabina De Geest, Olivier De Rougemont, Michael Dickenmann, Joëlle Lynn Dreifuss, Michel Duchosal, Thomas Fehr, Nicola Franscini, Christian Garzoni, Paola Gasche Soccal, Christophe Gaudet, Nicolas Goossens, Karine Hadaya, Jörg Halter, Dominik Heim, Christoph Hess, Sven Hillinger, Hans Hirsch, Patricia Hirt, Günther Hofbauer, Uyen Huynh-Do, Franz Immer, Michael Koller (Head of the data center), Mirjam. Laager, Bettina Laesser, Roger Lehmann, Alexander Leichtle, Christian Lovis, Oriol Manuel, Hans-Peter Marti, Pierre Yves Martin, Michele Martinelli, Valérie McLin, Katell Mellac, Aurelia Mercay, Karin Mettler, Nicolas Mueller (Chairman Scientific Committee), Antonia Müller, Thomas Müller, Ulrike Müller-Arndt, Beat Müllhaupt, Mirjam Nägeli, Graziano Oldani, Manuel Pascual (Executive office), Klara Posfay-Barbe, Juliane Rick, Anne Rosselet, Simona Rossi, Silvia Rothlin, Frank Ruschitzka, Urs Schanz, Aurelia Schnyder, Macé Schuurmans, Thierry Sengstag, Federico Simonetta, Katharina Staufer, Susanne Stampf, Jürg Steiger (Head, Excecutive office), Guido Stirniman, Ueli Stürzinger, Christian Van Delden (Executive office), Jean-Pierre Venetz, Julien Vionnet,Madeleine Wick (STCS coordinator), Markus Wilhlem, Patrick Yerly

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: kidney transplantation, donor specific antibodies, abmr, graft loss, virtual cross-match, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundPre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).MethodsWe investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.ResultsPre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR.ConclusionOur results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.

وصف الملف: electronic resource

Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1005790/full; https://doaj.org/toc/1664-3224

URL الوصول: https://doaj.org/article/d4470ae796694141bd821317fd2f95c7

المؤلفون: Liliane Borik-Heil, Georg Endler, Walther Parson, Andreas Zuckermann, Lisa Schnaller, Keziban Uyanik-Ünal, Peter Jaksch, Georg Böhmig, Daniel Cejka, Katharina Staufer, Elisabeth Hielle-Wittmann, Susanne Rasoul-Rockenschaub, Peter Wolf, Raute Sunder-Plassmann, Alexandra Geusau

المصدر: Cancers, Vol 15, Iss 3, p 864 (2023)

مصطلحات موضوعية: keratinocyte cancer, solid organ transplant recipients, immunosuppression, UV burden, skin aging, MC1R, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: The risk of keratinocyte cancer is determined by intrinsic and extrinsic factors, which also influence skin aging. Few studies have linked skin aging and UV exposure with the incidence of non-melanoma skin cancer (NMSC). We evaluated signs of actinic skin damage and aging, individual UV burden, and melanocortin-1 receptor (MC1R) variants. A total of 194 organ transplant recipients (OTR) who suffered from NMSC were compared to 194 tumor-free controls matched for gender, age, type of transplanted organ, post-transplantation (TX) period, and immunosuppressive therapy. Compared with the cases, the controls scored higher in all skin aging scores and there were no differences in UV burden except for intentional whole-body UV exposure for specific UV scenarios and periods of life in favor of cases. The number of NMSCs correlated with all types of skin aging scores, the extent of intentional sun exposure, older age, longer post-TX period, shorter interval from TX to first NMSC, and specific MC1R risk groups. Multivariable models revealed a 7.5-fold risk of developing NMSC in individuals with actinic keratosis; 4.1- or 3.6-fold in those with green or blue eyes, respectively; and a 1.9-fold increased risk in the MC1R medium- + high-risk group. In the absence of skin aging contributing to NMSC development, certain MC1R risk types may identify OTR at risk for high tumor burden.

وصف الملف: electronic resource

Relation: https://www.mdpi.com/2072-6694/15/3/864; https://doaj.org/toc/2072-6694

URL الوصول: https://doaj.org/article/b14332e45b8a4179b4f6600eecc01e42

المؤلفون: Katharina Staufer

المصدر: International Journal of Molecular Sciences, Vol 21, Iss 22, p 8586 (2020)

مصطلحات موضوعية: cystic fibrosis-related liver disease, CFTR modulators, ursodeoxycholic acid, liver transplantation, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Cystic Fibrosis-related liver disease (CFLD) has become a leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF), and affects children and adults. The understanding of the pathogenesis of CFLD is key in order to develop efficacious treatments. However, it remains complex, and has not been clarified to the last. The search for a drug might be additionally complicated due to the diverse clinical picture and lack of a unified definition of CFLD. Although ursodeoxycholic acid has been used for decades, its efficacy in CFLD is controversial, and the potential of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators and targeted gene therapy in CFLD needs to be defined in the near future. This review focuses on the current knowledge on treatment strategies for CFLD based on pathomechanistic viewpoints.

وصف الملف: electronic resource

Relation: https://www.mdpi.com/1422-0067/21/22/8586; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067

URL الوصول: https://doaj.org/article/12776ac859fd45aaa9342d2b036c1f19

المؤلفون: Katharina Staufer, Emina Halilbasic, Michael Trauner, Lili Kazemi-Shirazi

المصدر: International Journal of Molecular Sciences, Vol 15, Iss 8, Pp 13529-13549 (2014)

مصطلحات موضوعية: cystic fibrosis, bile acid transporters, gut liver axis, non-invasive diagnostics, cholestasis, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Due to improved medical care, life expectancy in patients with cystic fibrosis (CF) has veritably improved over the last decades. Importantly, cystic fibrosis related liver disease (CFLD) has become one of the leading causes of morbidity and mortality in CF patients. However, CFLD might be largely underdiagnosed and diagnostic criteria need to be refined. The underlying pathomechanisms are largely unknown, and treatment strategies with proven efficacy are lacking. This review focuses on current invasive and non-invasive diagnostic standards, the current knowledge on the pathophysiology of CFLD, treatment strategies, and possible future developments.

وصف الملف: electronic resource

Relation: http://www.mdpi.com/1422-0067/15/8/13529; https://doaj.org/toc/1422-0067

URL الوصول: https://doaj.org/article/02d5d1c3303440569d5562e6c20b4cb7

المؤلفون: Katharina Staufer, Gabriela Berlakovich

المصدر: European Medical Journal Hepatology, Vol 2, Iss 1, Pp 86-90 (2014)

مصطلحات موضوعية: abstention period, alcohol markers, alcoholic liver disease, liver transplantation, Relapse, Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: Liver transplantation for alcoholic liver disease (ALD) is controversially discussed. Although overall survival after liver transplantation is similar to other indications, long-term survival is significantly reduced in patients with recurrence of excessive alcohol consumption. Criteria of transplant eligibility and prediction of risk of alcohol relapse after transplantation are the core concerns in this setting. Most transplant centres therefore require an abstention period of 6 months prior to listing. However, data on the ‘6-month rule’ as a surrogate parameter for prediction of relapse are conflicting, and first reports on liver transplantation in highly selected patients with acute alcoholic hepatitis without response to medical treatment are promising. Therefore, a thorough pre-transplant evaluation by an experienced addiction specialist in addition to regular counselling and a highly supportive social surrounding after transplantation seem to be the key factors for long-term survival in ALD patients.

وصف الملف: electronic resource

Relation: http://emjreviews.com/wp-content/uploads/Liver-Transplantation-for-Alcoholic-Liver-Disease-%E2%80%93-Time-for-a-paradigm-shift.pdf; https://doaj.org/toc/2053-4221

URL الوصول: https://doaj.org/article/39fc83a8a471424ab6355c3c45144ad7

المؤلفون: Marlene Wewalka, Andreas Drolz, Katharina Staufer, Thomas M. Scherzer, Valentin Fuhrmann, Christian Zauner

المصدر: Case Reports in Critical Care, Vol 2011 (2011)

مصطلحات موضوعية: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9

الوصف: Khat is a drug widely used in the Horn of Africa and the Arabian Peninsula. Khat leaves contain, among other substances, the psychoactive alkaloid cathinone, which induce central nervous system stimulation leading to euphoria, hyperactivity, restlessness, and insomnia. However, it also could cause psychological adverse effects such as lethargy, sleepiness, psychoses, and depression necessitating pharmacologic treatment. Here we report the case of a 35-year-old man from Somalia who became unconscious and developed aspiration pneumonia and subsequent ARDS after excessive consumption of khat leaves. His unconsciousness was possibly caused by the sleepiness developed after khat consumption and a benzodiazepine intake by the patient himself. Thus, khat-induced adverse effects should not primarily be treated pharmacologically, but patients should be urged to quit khat consumption in order to eliminate or, at least, reduce the severity of present psychological adverse effects.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2090-6420; https://doaj.org/toc/2090-6439

URL الوصول: https://doaj.org/article/d5e1aeec3de54ff7814bb4b5bf19df1b