Petra Kloeters-Plachky

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (31)250.67 Total impact

  • C Rupp · AK Rupp · P Sauer · KA Bode · Y Leopold · P Kloeters-Plachky · KH Weiss · P Altevogt · W Stremmel · DN Gotthardt

    No preview · Article · Jan 2015 · Zeitschrift für Gastroenterologie
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    ABSTRACT: In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180±62 s with Col-Epi and 160±70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥150/nL and hematocrit ≥27.0%, pathological PFA-100 results were found. In thrombocytopenic (<150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3±235.9% vs. 338.7±151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.
    Full-text · Article · Nov 2014 · PLoS ONE
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    ABSTRACT: Background and study aims: To determine the importance of bacteriobilia and fungibilia in patients with endoscopic treatment of biliary complications after orthotopic liver transplantation (OLT). Patients and methods: In a prospective study at a tertiary center, 213 patients underwent 857 endoscopic retrograde cholangiographies (ERCs) after OLT. Findings at first ERC were: anastomotic stricture in 24.4%, nonanastomotic stricture in 18.3%, leakage in 11.3%, and gallstones in 4.7%. Results: Bile samples from first ERC showed Gram-positive bacterial isolates in 102/180 (57%) and Gram-negative in 44/180 (24%). Main species were Enterococcus spp. (40%; 72/180) and Escherichia coli (10%; 18 /180). Enteric bacteria (present in 47%) and Candida spp. (present in 18%) were both associated with clinical signs of cholangitis, but not with laboratory signs of inflammation. Multiresistant strains (present in 12% of samples) showed no association with clinical or laboratory parameters. Detection of microbiological isolates was independent of endoscopic findings and treatment. In patients with successful endoscopic intervention, the actuarial survival free of retransplantation was significantly lower in those with detection of enteric bacteria, being 51.8 months (95% confidence interval [CI] 42.9-60.6) vs. 62.9 months (95% CI 59.1-66.7); P = 0.025). Fungibilia was associated with significantly lower actuarial retransplantation-free survival, independently of successful endoscopic treatment (mean 35.1 months [95% CI 23.5-46.7] vs. 53.1 months [(95% CI 48.0-58.2]; P = 0.019). Conclusions: Bacteriobilia and fungibilia can frequently be detected by routine microbiological sampling in patients after OLT. Regular bile sampling is recommended since the presence of difficult-to-treat multiresistant strains is unpredictable. Survival is affected by this altered biliary microbiological environment after OLT.
    No preview · Article · Nov 2013 · Endoscopy
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    ABSTRACT: To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis (PSC) and secondary sclerosing cholangitis (SSC). Intrahepatic bile specimens collected via endoscopic retrograde cholangiography from 41 patients were analyzed. Fourteen of these patients were diagnosed with PSC, 10 with SSC, 11 with choledocholithiasis or no identifiable biliary disease, and 6 with cholangiocellular carcinoma (CCC). Bile acid, cholesterol, protein, and bilirubin contents as well as pancreas lipase activity in bile were determined by biochemical methods. Phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) species were quantified using nano-electrospray ionization tandem mass spectrometry. Bile from all the examined patient groups showed a remarkably similar PC and LPC species composition, with only minor statistical differences. Total biliary PC concentrations were highest in controls (8030 ± 1843 μmol/L) and lowest in patients with CCC (1969 ± 981 μmol/L) (P = 0.005, controls vs SSC and CCC, respectively, P < 0.05). LPC contents in bile were overall low (4.2% ± 1.8%). Biliary LPC/PC ratios and ratios of biliary PC to bilirubin, PC to cholesterol, PC to protein, and PC to bile acids showed no intergroup differences. PC and LPC profiles being similar in patients with or without sclerosing cholangitis, these phospholipids are likely not of major pathogenetic importance in this disease group.
    No preview · Article · Sep 2013 · World Journal of Gastroenterology

  • No preview · Article · May 2013 · Gastroenterology
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    Dataset: Table S1
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    ABSTRACT: List of bile duct-derived bile proteins identified by mass spectrometry including additional information on predicted protein characteristics. (DOCX)
    Preview · Dataset · Jan 2012
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    Dataset: Table S2
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    ABSTRACT: List of predicted bile duct-derived bile proteins separated by a Mascot score >100 or <100. (DOCX)
    Preview · Dataset · Jan 2012
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    Dataset: Table S4
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    ABSTRACT: List of pathways to which duct-derived bile proteins belong. (DOCX)
    Preview · Dataset · Jan 2012
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    Dataset: Table S3
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    ABSTRACT: List of bile duct-derived bile proteins identified with a Mascot score <100. (DOCX)
    Preview · Dataset · Jan 2012
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    ABSTRACT: Bile analysis has the potential to serve as a surrogate marker for inflammatory and neoplastic disorders of the biliary epithelium and may provide insight into biliary pathophysiology and possible diagnostic markers. We aimed to identify biliary protein markers of patients with primary sclerosing cholangitis (PSC) by a proteomic approach. Bile duct-derived bile samples were collected from PSC patients (n = 45) or patients with choledocholithiasis (n = 24, the control group). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to analyse the proteins, 2-D-gel patterns were compared by densitometry, and brush cytology specimens were analysed by RT-PCR. A reference bile-duct bile proteome was established in the control group without signs of inflammation or maligancy comprising a total of 379 non-redundant biliary proteins; 21% were of unknown function and 24% had been previously described in serum. In PSC patients, the biliary S100A9 expression was elevated 95-fold (p<0.005), serum protein expression was decreased, and pancreatic enzyme expression was unchanged compared to controls. The S100A9 expression was 2-fold higher in PSC patients with high disease activity than in those with low activity (p<0.05). The brush cytology specimens from the PSC patients with high disease activity showed marked inflammatory activity and leukocyte infiltration compared to the patients with low activity, which correlated with S100A9 mRNA expression (p<0.05). The bile-duct bile proteome is complex and its analysis might enhance the understanding of cholestatic liver disease. Biliary S100A9 levels may be a useful marker for PSC activity, and its implication in inflammation and carcinogenesis warrants further investigation.
    Full-text · Article · Jan 2012 · PLoS ONE
  • G Rudolph · D N Gotthardt · P Kloeters-Plachky · H Kulaksiz · P Schirmacher · A Stiehl
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    ABSTRACT: Patients with PSC and IBD have a high incidence of colonic carcinomas (CRC), and the annual incidence of CRC increases with duration of disease. UDCA treatment has been suggested to reduce colonic dysplasias and carcinomas. The annual incidence of colorectal carcinomas after long-term UDCA treatment was studied. Patients included in a prospective study on the outcome after ursodeoxycholic acid (UDCA) treatment were evaluated. A total of 120 of 171 PSC patients included had IBD (108 UC and 12 CD). All patients were treated with UDCA for a median time of 6.7 years. Seven patients with PSC and IBD developed a CRC yielding a prevalence of 5.8%. In years 0-3 (n = 120) after the start of UDCA, the annual incidence rate of CRC was 0.62/100 patient years; in years 3-6 (n = 93) it increased to 1.28 and decreased thereafter in years 6-9 (n = 67) to 1.17, then in years 9-12 (n = 42) to 0 and after >12 years (n = 24) it remained 0. In PSC with IBD, Kaplan-Meier estimate of CRC formation increased with time in the first years of treatment and reached a plateau after 9 years; after treatment for ≥ 9 years, no further CRC were observed. After the start of UDCA, the annual incidence of CRC increased up to 6 years and subsequently decreased. In PSC with IBD treated with UDCA, most colonic carcinomas develop in the first years after the start of treatment.
    No preview · Article · Jun 2011 · Digestive Diseases and Sciences
  • C Rupp · D Riedel · T Giese · L Reinhard · KH Weiss · P Kloeters-Plachky · P Schirmacher · W Stremmel · P Sauer · DN Gotthardt

    No preview · Article · Jan 2011 · Zeitschrift für Gastroenterologie
  • Gerda Rudolph · Daniel Gotthardt · Petra Kloeters-Plachky · Daniel Rost · Hasan Kulaksiz · Adolf Stiehl
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    ABSTRACT: In patients with primary sclerosing cholangitis (PSC) treated with ursodeoxycholic acid (UDCA), dominant stenoses are associated with reduced survival free of liver transplantation and the role of inflammatory bowel disease (IBD) in such patients is unclear. In the present study the influence of IBD on the outcome in patients with and without dominant stenosis has been evaluated. In a prospective study, 171 patients were followed for up to 20 years. All patients were treated with ursodeoxycholic acid; patients with dominant stenosis in addition were treated endoscopically. A total of 97 out of 171 patients had or developed dominant bile duct stenoses and 96 out of 97 were treated endoscopically. In patients with dominant stenosis without IBD, no carcinoma was found whereas all six bile duct and two gallbladder carcinomas and 6/7 colo-rectal carcinomas were found in patients with dominant stenosis with IBD (p=0.012). In patients without dominant stenosis but with IBD, 1 out of 7 had colo-rectal carcinoma. In patients with dominant stenosis without IBD (n=30), actuarial survival free of liver transplantation at 18 years was 77.8% and in those with dominant stenosis and inflammatory bowel disease (n=67) it was 23.0% (p=0.045). In PSC patients without dominant stenosis and without IBD (n=21), actuarial survival free of liver transplantation at 18 years was 68.2% and in those with inflammatory bowel disease (n=53) it was 78.4% (n.s.). In patients without dominant stenosis, IBD had no effect on the incidence of carcinomas and survival. Only patients with dominant stenosis with additional IBD had an increased carcinoma rate. This may contribute to the reduced survival free of liver transplantation in such patients.
    No preview · Article · Aug 2010 · Journal of Hepatology
  • Gerda Rudolph · Daniel Gotthardt · Petra Kloeters-Plachky · Hasan Kulaksiz · Adolf Stiehl

    No preview · Article · May 2010 · Gastroenterology
  • L. Reinhard · D. Riedel · P. Klöters-Plachky · K. H. Weiss · W. Stremmel · P. Sauer · D. Gotthardt

    No preview · Article · Apr 2010 · Journal of Hepatology
  • Daniel N Gotthardt · Gerda Rudolph · Petra Klöters-Plachky · Hasan Kulaksiz · Adolf Stiehl
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    ABSTRACT: Primary sclerosing cholangitis is characterized by progressive fibrotic inflammation and obliteration of intra- and/or extrahepatic bile ducts. Total or subtotal stenoses of major bile ducts are associated with reduced survival. To evaluate the outcome after long-term endoscopic treatment. Prospective, single-center study. Tertiary care academic medical center. A total of 171 patients treated with ursodeoxycholic acid were followed for as long as 20 years. At entry, 20 patients had dominant stenoses, and during a median follow-up period of 7.1 years, dominant stenosis developed in another 77. Ninety-six patients with dominant stenoses were treated by repeated balloon dilation; 5 patients with complete obstruction with bacterial cholangitis were stented. Survival free of liver transplantation, number of procedures, complications. In total, 500 balloon dilations were performed and 5 stents were placed. Complications were pancreatitis (2.2%), bacterial cholangitis (1.4%), and bile duct perforation (0.2%); there were no deaths. Repeated endoscopic interventions allowed the preservation of a functioning common bile duct and of at least 1 hepatic duct up to 2 cm above the bifurcation in all patients. Progression of intrahepatic bile duct and liver disease led to the need for liver transplantation in 22 of 96 patients. Five years after the first dilation of a dominant stenosis, the survival free of liver transplantation rate was 81%, and after 10 years, it was 52%. Single-center study, no control group, primary end-stage liver disease excluded. Repeated endoscopic balloon dilations of dominant stenoses allow the preservation of a functioning common bile duct for many years.
    No preview · Article · Mar 2010 · Gastrointestinal endoscopy
  • Gerda Rudolph · Daniel Gotthardt · Petra Klöters-Plachky · Hasan Kulaksiz · Daniel Rost · Adolf Stiehl
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    ABSTRACT: In primary sclerosing cholangitis (PSC) dominant stenoses are frequently associated with bacterial, and in part, also fungal infections of the bile ducts. In the present study, the influence of dominant stenoses and of biliary infections on the long-term outcome was studied. In a prospective study, 171 patients were followed up for 20 years. All patients were treated with ursodeoxycholic acid. Dominant stenoses were treated endoscopically and during endoscopic procedures, bile was obtained for microbiologic analysis. Of the 171 patients, 97 had or developed major bile duct stenoses and 96/97 were treated endoscopically. In the 55/97 patients with dominant stenosis, bile samples were obtained and of these, 41/55 had bacteria, five had also Candida and 2/55 had only Candida in their bile. Survival free of liver transplantation in patients without dominant stenosis at 18 years was 73.1% and of patients with dominant stenosis was 25.0% (p=0.011). Bacteria in bile had no effect on survival whereas Candida in bile was associated with reduced survival (p=0.025). In patients with dominant stenosis, survival free of liver transplantation is reduced. Bacteria in bile do not worsen the outcome if dominant stenoses are opened endoscopically and infection is adequately treated with antibiotics. Candida in bile is associated with a poor prognosis and these patients need liver transplantation relatively soon.
    No preview · Article · Apr 2009 · Journal of Hepatology
  • Daniel Rost · P Kloeters-Plachky · A Stiehl
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    ABSTRACT: Bile salts may initiate or aggravate cholestasis in man. Infusion of Taurochenodeoxycholate (TCDCA) represents a model of bile salt-induced cholestasis in rat. The events leading to cholestasis are incompletely understood. The canalicular conjugate export pump Mrp2 is the major driving force for the bile salt-independent bile flow. Redistribution of Mrp2 has been suggested to cause reduction in bile flow in others models of acute cholestasis (i.e. endotoxin, phalloidin, GSH-depletion). We have studied the effects of TCDCA on the distribution of Mrp2 and P-glycoproteins with respect to changes in the actin cytoskeleton and actin associated proteins radixin and ZO-1. Bile duct cannulated rats were infused with TCDCA (0.1 and 0.4 micromol/min/100g body weight) and bile flow was measured. After 30 min livers were removed and distribution of Mrp2, P-glycoproteins, actin, actin-associated radixin and ZO1 were studied by immunofluorescence analysis. TCDCA at subcholestatic amounts (0.1 micromol/min/100 g body weight) led to distortion and dilation of the canaliculi which was apparent in actin, ZO-1, and Mrp2 fluorescence. Administration of higher amounts of TCDCA (0.4 micromol/min/100g body weight) led to a reduction of bile flow to 31 % of control bile flow. Radixin, which localized strictly to the plasmamembrane in controls, was detected in intracellular structures partially colocalizing with actin aggregates especially at the sinusoidal membranes as visualized by double-immunofluorescence staining. Mrp2 appeared in pericanalicular membrane structures in cholestatic animals whereas P-glycoproteins remained unchanged under these conditions. CONCLUSIONS: Bile salt-induced cholestasis is associated with changes of the actin cytoskeleton and actin binding protein radixin and a retrieval of the canalicular export pump Mrp2.
    No preview · Article · Aug 2008 · European journal of medical research
  • Daniel Gotthardt · Gerda Rudolph · Petra Kloeters-Plachky · Peter Sauer · Hasan Kulaksiz · Adolf Stiehl

    No preview · Article · Apr 2008 · Gastroenterology
  • Gerda Rudolph · Petra Kloeters-Plachky · Daniel Rost · Adolf Stiehl
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    ABSTRACT: Cholangiocarcinoma represents a serious complication of primary sclerosing cholangitis. Ursodeoxycholic acid may possibly influence the incidence of cholangiocarcinoma in man. The aim of this study was to evaluate the incidence rate of cholangiocarcinoma in a large group of primary sclerosing cholangitis patients after long-time treatment with ursodeoxycholic acid. From May 1987 up to May 2005 a total of 150 patients with primary sclerosing cholangitis but without evidence of cholangiocarcinoma at entry were included in the study. All patients were treated with ursodeoxycholic acid and controls were performed in at least yearly intervals. The median treatment time of the 150 patients was 6.4 years. Altogether five patients developed a cholangiocarcinoma during treatment yielding a rate of 3.3%. The patients developed 0.58 cholangiocarcinoma per 100 patient-years in years 0-2.5, 0.59 cholangiocarcinoma in years 2.5-8.5, and no cholangiocarcinoma thereafter up to 18 years after entry into the study. The Kaplan-Meier estimate of cholangiocarcinoma incidence during ursodeoxycholic acid treatment reached a plateau after 8.3 years. The annual incidence rate of cholangiocarcinoma in primary sclerosing cholangitis treated with ursodeoxycholic acid is lower than expected and decreases with time of treatment.
    No preview · Article · Jul 2007 · European Journal of Gastroenterology & Hepatology

Publication Stats

698 Citations
250.67 Total Impact Points

Institutions

  • 1995-2014
    • Universität Heidelberg
      • University Hospital of Internal Medicine
      Heidelburg, Baden-Württemberg, Germany
  • 2010
    • Heidelberg University
      تيفين، أوهايو, Ohio, United States