• Deutsch
Login

Open Access

  • Home
  • Search
  • Browse
  • Publish
  • FAQ

Refine

Author

  • Waidmann, Oliver (21)
  • Zeuzem, Stefan (19)
  • Piiper, Albrecht (9)
  • Kronenberger, Bernd (8)
  • Bechstein, Wolf Otto (5)
  • Filmann, Natalie (5)
  • Trojan, Jörg (5)
  • Ferstl, Philip (4)
  • Grammatikos, Georgios (4)
  • Kempf, Volkhard A. J. (4)
+ more

Year of publication

  • 2018 (5)
  • 2021 (3)
  • 2012 (2)
  • 2013 (2)
  • 2014 (2)
  • 2015 (2)
  • 2020 (2)
  • 2009 (1)
  • 2011 (1)
  • 2017 (1)
+ more

Document Type

  • Article (21)

Language

  • English (21)

Has Fulltext

  • yes (21)

Is part of the Bibliography

  • no (21)

Keywords

  • Hepatocellular carcinoma (2)
  • Liver diseases (2)
  • liver transplantation (2)
  • Adenylyl cyclase (1)
  • Alcoholic liver disease (1)
  • Biliary physiology (1)
  • Cancer (1)
  • Cancer treatment (1)
  • Cirrhosis (1)
  • Colon cancer (1)
+ more

Institute

  • Medizin (21)
  • Biowissenschaften (3)
  • Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (2)
  • Biochemie und Chemie (1)
  • Georg-Speyer-Haus (1)
  • Institut für Ökologie, Evolution und Diversität (1)
  • Interdisziplinäres Zentrum für Neurowissenschaften Frankfurt (IZNF) (1)
  • Pharmazie (1)
  • Senckenbergische Naturforschende Gesellschaft (1)

21 search hits

  • 1 to 10
  • 10
  • 20
  • 50
  • 100

Sort by

  • Year
  • Year
  • Title
  • Title
  • Author
  • Author
Molecular surveillance of carbapenem-resistant gram-negative bacteria in liver transplant candidates (2021)
Schultze, Tilman ; Ferstl, Philip ; Villinger, David ; Hogardt, Michael ; Bechstein, Wolf Otto ; Göttig, Stephan ; Wichelhaus, Thomas A. ; Zeuzem, Stefan ; Trebicka, Jonel ; Waidmann, Oliver ; Welker, Martin-Walter ; Kempf, Volkhard A. J.
Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes. Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts. Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN. Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
Serum autotaxin is a parameter for the severity of liver cirrhosis and overall survival in patients with liver cirrhosis : a prospective cohort study (2014)
Pleli, Thomas ; Martin, Daniel ; Kronenberger, Bernd ; Brunner, Friederike ; Köberle, Verena ; Grammatikos, Georgios ; Farnik, Harald ; Martinez, Yolanda ; Finkelmeier, Fabian ; Labocha, Sandra ; Ferreirós Bouzas, Nerea ; Zeuzem, Stefan ; Piiper, Albrecht ; Waidmann, Oliver
Background: Autotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients. Methods: Patients with liver cirrhosis were prospectively enrolled and followed until death, liver transplantation or last contact. Blood samples drawn at the day of inclusion in the study were assessed for ATX content by an enzyme-linked immunosorbent assay. ATX levels were correlated with the stage as well as complications of cirrhosis. The prognostic value of ATX was investigated by uni- and multivariate Cox regression analyses. LPA concentration was determined by liquid chromatography-tandem mass spectrometry. Results: 270 patients were enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as compared to healthy subjects (0.814±0.42 mg/l vs. 0.258±0.40 mg/l, P<0.001). Serum ATX levels correlated with the Child-Pugh stage and the MELD (model of end stage liver disease) score and LPA levels (r = 0.493, P = 0.027). Patients with hepatic encephalopathy (P = 0.006), esophageal varices (P = 0.002) and portal hypertensive gastropathy (P = 0.008) had higher ATX levels than patients without these complications. Low ATX levels were a parameter independently associated with longer overall survival (hazard ratio 0.575, 95% confidence interval 0.365–0.905, P = 0.017). Conclusion: Serum ATX is an indicator for the severity of liver disease and the prognosis of cirrhotic patients.
Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma (2011)
Bihrer, Verena ; Waidmann, Oliver ; Friedrich-Rust, Mireen ; Forestier, Nicole ; Susser, Simone ; Haupenthal, Jörg ; Welker, Martin ; Shi, Ying ; Peveling-Oberhag, Jan Franz-Josef ; Polta, Andreas ; Wagner, Michael von ; Radeke, Heinfried Hermann ; Sarrazin, Christoph ; Trojan, Jörg ; Zeuzem, Stefan ; Kronenberger, Bernd ; Piiper, Albrecht
Background: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC. Methodology/Principal Findings: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = −0.494, P = 0.00002), alanine aminotransferase (ALT) (r = −0.309, P = 0.007), aspartate aminotransferase (r = −0.495, P = 0.000007), bilirubin (r = −0.362, P = 0.002), international normalized ratio (r = −0.338, P = 0.034) and γ-glutamyltransferase (r = −0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dCT of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%. Conclusions/Significance: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC.
Reduced efficacy of the plk1 inhibitor bi 2536 on the progression of hepatocellular carcinoma due to low intratumoral drug levels (2014)
Haupenthal, Jörg ; Bihrer, Verena ; Korkusuz, Hüdayi ; Kollmar, Otto ; Schmithals, Christian ; Kriener, Susanne ; Engels, Knut ; Pleli, Thomas ; Benz, Alexander ; Canamero, Marta ; Longerich, Thomas ; Kronenberger, Bernd ; Richter, Swantje ; Waidmann, Oliver ; Vogl, Thomas J. ; Zeuzem, Stefan ; Piiper, Albrecht
Highly promising preclinical data obtained in cultured cells and in nude mice bearing xenografts contrast with the rather modest clinical efficacy of Polo-like kinase 1 (Plk1) inhibitors. In the present study, we investigated if Plk1 might be a suitable target in hepatocellular carcinoma (HCC) and if a genetically engineered mouse tumor model that well reflects the tumor cell and micro-environmental features of naturally occurring cancers might be suitable to study anti-Plk1 therapy. Analysis of Plk1 expression in human HCC samples confirmed that HCC express much higher Plk1 levels than the adjacent normal liver tissue. Inhibition of Plk1 by an adenovirus encoding for a short hairpin RNA against Plk1 or by the small-molecule inhibitor BI 2536 reduced the viability of HCC cell lines and inhibited HCC xenograft progression in nude mice. Treatment of transforming growth factor (TGF) α/c-myc bitransgenic mice with BI 2536 during hepatocarcinogenesis reduced the number of dysplastic foci and of Ki-67-positive cells within the foci, indicating diminished tumorigenesis. In contrast, BI 2536 had no significant effect on HCC progression in the transgenic mouse HCC model as revealed by magnetic resonance imaging. Measurement of BI 2536 by mass spectrometry revealed considerably lower BI 2536 levels in HCC compared with the adjacent normal liver tissue. In conclusion, low intratumoral levels are a novel mechanism of resistance to the Plk1 inhibitor BI 2536. Plk1 inhibitors achieving sufficient intratumoral levels are highly promising in HCC treatment.
Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study (2012)
Kronenberger, Bernd ; Rudloff, Ina ; Bachmann, Malte ; Brunner, Friederike ; Kapper, Lisa ; Filmann, Natalie ; Waidmann, Oliver ; Herrmann, Eva ; Pfeilschifter, Josef Martin ; Zeuzem, Stefan ; Piiper, Albrecht ; Mühl, Heiko
Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P <0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P <0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis.
Serum sphingolipid variations associate with hepatic decompensation and survival in patients with cirrhosis (2015)
Grammatikos, Georgios ; Ferreiròs, Nerea ; Waidmann, Oliver ; Bon, Dimitra ; Schroeter, Sirkka ; Koch, Alexander ; Herrmann, Eva ; Zeuzem, Stefan ; Kronenberger, Bernd ; Pfeilschifter, Josef Martin
Background: Sphingolipids constitute bioactive molecules with functional implications in liver homeostasis. Particularly, ablation of very long chain ceramides in a knockout mouse model has been shown to cause a severe hepatopathy. Methods: We aimed to evaluate the serum sphingolipid profile of 244 patients with cirrhosis prospectively followed for a median period of 228±217 days via mass spectrometry. Results: We thereby observed a significant decrease of long and very long chain ceramides, particularly of C24ceramide, in patients with increasing severity of cirrhosis (p<0.001). Additionally, hydropic decompensation, defined by clinical presentation of ascites formation, was significantly correlated to low C24ceramide levels (p<0.001) while a significant association to hepatic decompensation and poor overall survival was observed for low serum concentrations of C24ceramide (p<0.001) as well. Multivariate analysis further identified low serum C24ceramide to be independently associated to overall survival (standard beta = -0.001, p = 0.022). Conclusions: In our current analysis serum levels of very long chain ceramides show a significant reciprocal correlation to disease severity and hepatic decompensation and are independently associated with overall survival in patients with cirrhosis. Serum sphingolipid metabolites and particularly C24ceramide may constitute novel molecular targets of disease severity, hepatic decompensation and overall prognosis in cirrhosis and should be further evaluated in basic research studies.
Circulating hypoxia marker carbonic anhydrase IX (CA9) in patients with hepatocellular carcinoma and patients with cirrhosis (2018)
Finkelmeier, Fabian ; Canli, Özge ; Peiffer, Kai-Henrik ; Walter, Dirk ; Tal, Andrea ; Koch, Christine ; Pession, Ursula ; Vermehren, Johannes ; Trojan, Jörg ; Zeuzem, Stefan ; Piiper, Albrecht ; Greten, Florian ; Grammatikos, Georgios ; Waidmann, Oliver
Background and aims: Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated serum CA9 levels in HCC and cirrhosis patients. Methods: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated. Results: 215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had hid significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (>400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval (CI) 1.017–2.809, P = 0.043). Serum CA9 concentration in cirrhotic patients did not differ significantly from HCC patients. Higher CA9 levels in cirrhotic patients correlated with portal hypertension and esophageal varices. Patients with ethanol induced cirrhosis had the highest CA9 levels in both cohorts. Levels of CA9 did not correlate with immunohistochemical expression. Conclusions: We conclude that a high CA9 level is a possible prognostic indicator for a poor outcome in HCC patients. The high CA9 levels are probably mainly associated with portal hypertension. Ductular reactions might be a possible source of serum CA9.
AFP ratio predicts HCC recurrence after liver transplantation (2020)
Koch, Christine ; Bette, Theresa ; Waidmann, Oliver ; Filmann, Natalie ; Schrecker, Christopher ; Trojan, Jörg ; Weiler, Nina ; Vermehren, Johannes ; Schnitzbauer, Andreas ; Bechstein, Wolf Otto ; Zeuzem, Stefan ; Herrmann, Eva ; Welker, Martin-Walter
Background/aims: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels. Methods: We performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence. Results: 19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5. Conclusion: A rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.
Colonization with multidrug-resistant organisms is associated with in increased mortality in liver transplant candidates (2021)
Ferstl, Philip ; Filmann, Natalie ; Heilgenthal, Eva-Maria ; Schnitzbauer, Andreas ; Bechstein, Wolf Otto ; Kempf, Volkhard A. J. ; Villinger, David ; Schultze, Tilman ; Hogardt, Michael ; Stephan, Christoph ; Mutlak, Haitham ; Weiler, Nina ; Mücke, Marcus Maximilian ; Trebicka, Jonel ; Zeuzem, Stefan ; Waidmann, Oliver ; Welker, Martin-Walter
Objectives: Rising prevalence of multidrug-resistant organisms (MDRO) is a major health problem in patients with liver cirrhosis. The impact of MDRO colonization in liver transplantation (LT) candidates and recipients on mortality has not been determined in detail. Methods: Patients consecutively evaluated and listed for LT in a tertiary German liver transplant center from 2008 to 2018 underwent screening for MDRO colonization including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria (MDRGN), and vancomycin-resistant enterococci (VRE). MDRO colonization and infection status were obtained at LT evaluation, planned and unplanned hospitalization, three months upon graft allocation, or at last follow-up on the waiting list. Results: In total, 351 patients were listed for LT, of whom 164 (47%) underwent LT after a median of 249 (range 0–1662) days. Incidence of MDRO colonization increased during waiting time for LT, and MRDO colonization was associated with increased mortality on the waiting list (HR = 2.57, p<0.0001. One patients was colonized with a carbapenem-resistant strain at listing, 9 patients acquired carbapenem-resistant gram-negative bacteria (CRGN) on the waiting list, and 4 more after LT. In total, 10 of these 14 patients died. Conclusions: Colonization with MDRO is associated with increased mortality on the waiting list, but not in short-term follow-up after LT. Moreover, colonization with CRGN seems associated with high mortality in liver transplant candidates and recipients.
Combination of sorafenib and transarterial chemoembolization in selected patients with advanced-stage hepatocellular carcinoma: a retrospective cohort study at three german liver centers (2021)
Koch, Christine ; Göller, Markus ; Schott, Eckart ; Waidmann, Oliver ; Winkel, Mark op den ; Paprottka, Philipp Marius ; Zangos, Stephan ; Vogel, Thomas ; Bechstein, Wolf Otto ; Zeuzem, Stefan ; Kolligs, Frank Thomas ; Trojan, Jörg
Background and Aims. Systemic treatment with sorafenib has been the standard of care (SOC) in patients with advanced Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) for more than a decade. TACE has been reported to allow better local tumor control in selected patients with BCLC stage C HCC. Methods. A retrospective analysis of patients with BCLC stage C HCC that were treated with sorafenib and TACE was conducted; they were compared to BCLC stage C patients treated either with TACE or sorafenib in the same period of time outside a clinical trial. Results. A total of 201 patients with BCLC stage C were identified, who were treated with either sorafenib and TACE (group A; n = 54), sorafenib (group B; n = 82) or TACE (group C; n = 65). No significant difference in baseline characteristics was observed. Time to progression was 7.0 months (95% CI: 4.3–9.7), 4.1 months (95% CI: 3.6–4.7) and 5.0 months (95% CI: 2.9–7.1) in groups A, B and C, respectively, and overall survival was 16.5 months (95% CI: 15.0–18.1), 8.4 months (95% CI: 6.0–10.8) and 10.5 months (95% CI: 7.5–13.6), respectively (group A vs. group B: p < 0.001; group A vs. group C: p = 0.0023). Adverse events of grade 3/4 occurred in 34% of patients in group A. Conclusions. Although sorafenib is a SOC in patients with BCLC stage C HCC, TACE is frequently used as an additional locoregional treatment in selected patients. This combined approach resulted in a significant overall survival benefit in selected patients, although randomized trials have not yet proven this benefit.
  • 1 to 10

OPUS4 Logo

  • Contact
  • Imprint
  • Sitelinks