Maximilian Schöniger-hekele - Academia.edu (original) (raw)

Papers by Maximilian Schöniger-hekele

Zeitschrift Fur Gastroenterologie, May 1, 2005

Journal of Hepatology, 2000

Cytochrome P4502D6 (CYP2D6) is the target of liver kidney microsomal antibody type 1 (LKM1) both ... more Cytochrome P4502D6 (CYP2D6) is the target of liver kidney microsomal antibody type 1 (LKM1) both in autoimmune hepatitis (AIH) and hepatitis C virus (HCV) infection, but reactivity is not identical, CYP2D61-327 being more frequently recognised by AIH than HCV sera when compared to CYP2D61-317 (J HepatoI1999; 30:Suppl 1, 70). To characterise this region, we have expressed eukaryotically (Promega Ltd, UK) native CYP2D61.375 and two hybrid molecules, "where CYP2D6317.327 was replaced by homologous sequences of CYP2C9 and of HCV respectively, and used them as targets in a radioligand assay: CYP2D6317_327 GLLLMILHPDV CYP2 C 9310.320

Journal of Hepatology, 2004

Background and aims: Recently, a new generation of the carbohydratedeficient-transferrin (CDT 2.6... more Background and aims: Recently, a new generation of the carbohydratedeficient-transferrin (CDT 2.6%) assay has been developed, which measures asialo-, monosialo-and disialo transferrin, but excludes trisialotransferrin. That modification suggests higher sensitivity and specificity in detecting recent alcohol abuse and was evaluated in a group of patients with liver disease. Results were compared with that of the established CDT assay (CDT 4.7%). Patients and methods: Our study population consisted of 110 consecutive patients with liver disease of the following etiologies: chronic alcohol abuse [46.4%], chronic hepatitis C infection [22.7%], chronic hepatitis B infection [7.3%], haemochromatosis [3.6%], mechanical cholestasis [15.5%] and other liver diseases [4.6%]. The majority (72.7%, n=80) of our patients had liver cirrhosis. Results: In our population of liver disease patients the CDT 2.6% assay had a sensitivity of 72.7% and specificity of 58.1% for recent alcohol abuse at the published cutoff level of 2.6%. The positive predictive value was 34.0% and the negative predictive value was 87.8%. Sensitivity and specificity of the CDT 4.7% assay at the recommended cutoff level of 4.7% were similar, 77.3% and 49.3%, respectively. The positive and negative predictive values were 30.9% and 88.1%. CDT 4.7% levels increased significantly with higher Child-Pugh stages. Conclusion: The newly developed carbohydrate deficient transferrin test (CDT 2.6%) is of no advantage as compared to the established assay (CDT 4.7%) when used in a patient population with liver disease. In that population, the positive predictive value of CDT 2.6% is poor for detecting recent alcohol abuse.

International Congress Series, Apr 1, 2006

This study reports a case where early detection of graft-versus-host disease (GVHD) was possible ... more This study reports a case where early detection of graft-versus-host disease (GVHD) was possible by STR (short tandem repeat) analysis and demonstrates the value of this analysis for differential diagnosis. The aspects of artificial chimerism after solid organ transplantation for forensic investigations are pointed out.

Journal of Immunotherapy, Nov 1, 2002

Interferon (IFN)-gamma and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) enhance tumo... more Interferon (IFN)-gamma and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) enhance tumor immunogenicity. The authors assessed tolerability and effectiveness of a combination therapy of these recombinant human (rh) cytokines in patients with inoperable hepatocellular carcinoma (HCC). In a monocentric, open, nonrandomized pilot study, rhGM-CSF (5 microg/kg qd, Monday and Tuesday) and rhIFN-gamma (100 microg qd, Wednesday and Thursday) were subcutaneously administered in 9-week cycles. Primary objective was survival, as secondary outcomes volumetric changes of tumor mass and biologic parameters reflecting systemic immunologic or local tumor responses were measured. Only patients with complete response (CR), partial response (PR), or stable disease (SD) proceeded to new treatment cycles. Fifteen patients (median 63 years, range 46-74 years, all men) were enrolled. Survival after the first cycle was 80% with SD in 9 of 15 patients (60%). PR was detected in one patient after the second cycle. Two patients finished five treatment cycles. Overall survival at 26 and 52 weeks was 40% and 20%, respectively. Median survival in patients with inducible HLA-DR on hepatoma cells (40%) was increased (42 weeks, 27-100) as compared with HLA-DR negative cases (60%; 13 weeks, 8-23; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and a control group (p = 0.01). Parameters reflecting systemic immunomodulatory activities were not associated with clinical outcome. In 13 of 15 patients (87%), adverse events were reported, all less than grade 2 and none requiring therapy discontinuation. Immunotherapeutic approaches hold promise to prolong survival in selected patients with advanced HCC who respond by enhanced tumor immunogenicity.

Octreotide treatment of patients with hepatocellular carcinoma- a retrospective single centre con... more Octreotide treatment of patients with hepatocellular carcinoma- a retrospective single centre controlled study

Zeitschrift Fur Gastroenterologie, 2014

Zeitschrift für Gastroenterologie, 2017

Gut, 2001

Background and aims-We investigated the influence of baseline characteristics of patients with he... more Background and aims-We investigated the influence of baseline characteristics of patients with hepatocellular carcinoma (HCC) on prognosis and developed a multivariate Cox model predicting survival. All patients were from Central Europe. Methods-All 245 patients seen at the Department of Gastroenterology and Hepatology at the University of Vienna, Austria, from July 1991 to March 1998 were included in this retrospective study. Nineteen diVerent clinical characteristics and survival time from date of diagnosis were noted. Factors determining survival time were analysed by univariate and multivariate analysis using Cox proportional hazard regression models and a new classification model was constructed. The validity of this model was tested on an independent group of 89 patients, seen from April 1998 to September 1999. Results-Median survival in patients with HCC was 8.0 months. In a multivariate analysis bilirubin (>2 mg/dl), portal vein thrombosis, prothrombin time (<70%), alpha fetoprotein (>180 µg/l), tumour mass >50%, and enlarged lymph nodes were independent predictors of survival. A newly constructed Cox proportional hazard model (Vienna survival model for HCC=VISUM-HCC) identified three disease stages with diVerent durations of survival (median survival stage 1, 15.2 months; stage 2, 7.2 months; and stage 3, 2.6 months; p=0.00001). Applying the VISUM-HCC survival model to patients in Okuda stage 2 identified subgroups with an excellent and very poor prognosis for which diVerent treatment modalities should be oVered. Conclusions-Our patients with HCC had a poor median survival of eight months. Six easily measurable clinical variables were significant predictors of survival in patients with HCC. The new VISUM-HCC survival model may be useful for stratifying patients with HCC for various clinical treatment modalities.

Journal of Hepatology, 1998

Aims: We studied the prevalence of HGV-RNA in serum by reverse PCR and determined antibodies agai... more Aims: We studied the prevalence of HGV-RNA in serum by reverse PCR and determined antibodies against the envelope protein E2 of HGV by ELISA in 83 patients with welldefined autoimmune hepatitis (AM). Methods: HGV-RNA was detected by reverse transscription PCR with nested primers from the non-structural region 3. Sequence data were obtained by an automatic sequenzer. Anti-E2 antibody, a marker of past infection, was measured by ELISA. Results: HGV-RNA was found in 11 of 83 patients (13%) as compared with 2% of healthy controls (p=O.O12). Anti-E2 was observed in 15 (18%) patients which was not different from healthy controls (12 out of 93; ns.). Only 1 patient had both HGV-RNA and anti-E2 present in serum at the same time. HGV-RNA was found in 8% of type I AIH, but in 23% and 14% of type II and type III AIH, respectively. Conversely, 26% of type I, but only 12% and 7% of type II and type III AlH had anti-E2. Exposure to HGV (HGV-RNA+ or anti-E2+) was similar in all three types (34%, 35%, 2 1%)). Sequence analysis of HGV in the 11 positive patients revealed infection with only one single genotype of HGV (type 2b). Conclusions: Patients with AIH have an increased risk for HGV infection. Patients with type I AIH are more likely to show anti-E2 as a marker of past HGV infection. Only a single genotype of HGV-RNA was present in our population of patients with AIH.

Alimentary Pharmacology & Therapeutics, 2018

Background: Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP... more Background: Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. Aim: To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. Methods: (Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. Results: Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P = 0.353) nor mortality (log-rank: P = 0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL + NSBB vs EBL alone (log-rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log-rank: P<0.001). A decreased risk of death with EBL + NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6-months mortality (HR: 0.53, P = 0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P = 0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P = 0.567). Conclusions: EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6 months after EBL.

Gut Pathogens

Background: Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. Rapid urease ... more Background: Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. Rapid urease tests (RUT) are well established for the point-of-care, invasive diagnosis of H. pylori infection. The study aimed to evaluate the diagnostic performance of a new liquid RUT, the preOx-HUT, within a prospective cohort of treatment-naïve patients. Methods: The multicenter prospective clinical trial was conducted at nine Austrian centers for gastrointestinal endoscopy. Patients referred for a diagnostic upper gastrointestinal endoscopy underwent gastric biopsy sampling for routine histological evaluation, and in parallel, the preOx-HUT. Histology served as reference standard to evaluate the diagnostic performance of the preOx-HUT. Results: From January 2015 to January 2016, a total of 183 consecutive patients (54 males and 129 females, median age 50 years) were included. Endoscopy revealed pathological findings in 149/183 cases (81%), which were mostly gastritis (59%) and gastro-esophageal reflux disease (27%). H. pylori infection was detected by histology in 41/183 (22%) cases. In relation to histology, the preOx-HUT had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 80% and a negative predictive value of 96%. Performance of preOx-HUT was not affected significantly by concomitant PPI-use as present in 15% of cases (P = 0.73). Conclusions: This was the first study evaluating the preOx-HUT in a prospective, multicenter clinical setting. We found a high diagnostic accuracy for the point-of-care, invasive diagnostic test of H. pylori infection. Hence, this test may be a valuable diagnostic adjunct to the clinical presentation of patients with suspected H. pylori infection.

PLOS ONE

Background and aims The prevalence of Helicobacter pylori (H. pylori) tends to be lower in Wester... more Background and aims The prevalence of Helicobacter pylori (H. pylori) tends to be lower in Western countries such as central Europe compared with Asia. The virulence of H. pylori is influenced by its subtype composition, most importantly by the presence or absence of different types of cytotoxinassociated gene A(CagA). This study aimed to assess the prevalence of H. pylori and its respective CagA phenotype in a large retrospective cohort of patients with gastric cancer or duodenal ulcer at a Western tertiary referral institution. Methods H. pylori positive gastric biopsy samples from patients diagnosed with the afore mentioned diseases within the past 25 years were re-evaluated by histology for H. pylori and status of gastritis. Confirmed H. pylori positive cases were processed for immunohistochemistry (IHC) for H. pylori,CagA, and EastAsiantype CagA. Results The prevalence of H. pylori positive gastric biopsy samples decreased from 20.7% to 2.3% within the study period. Among the gastric cancer patients, the H. pylori positive rate was 16.6%, and didn't show significant changes over time (p = 0.38). Contrary, the H. pylori positive rate of duodenal ulcer decreased significantlyfrom 40% to 5% (p = 0.01). Within H. pylori positive groups ofboth diseases, CagA was highly detected at IHC (86% and 78%, respectively). Except for a few patients originating from East Asian countries, all CagA detected in this study were of Western type.

Gastrointestinal Endoscopy

Gastrointestinal Endoscopy, 2016

Gastrointestinal endoscopy, Jan 21, 2016

Accurate diagnosis of small gastric subepithelial tumors (SETs) is essential to assess their mali... more Accurate diagnosis of small gastric subepithelial tumors (SETs) is essential to assess their malignant potential. Endoscopic unroofing has been reported to yield sufficient tissue samples for histological evaluation. This study aimed to evaluate this technique regarding safety, diagnostic yield and potential therapeutic effects over time. This retrospective analysis of prospectively collected clinical data identified patients who underwent endoscopic unroofing at the Medical University of Vienna from January 2003 to December 2012. Demographic data, indications for endoscopic unroofing, intraprocedural adverse events, hospital stay, histological results and follow-up procedures were reviewed. A total of 14 patients (7 male, 7 female, median age 70 years, range 51 to 95 years) underwent endoscopic unroofing of 14 gastric SETs with a mean diameter of 26 ± 13 mm at endosonography (EUS). In 9 of 14 cases endoscopic unroofing was exclusively done for diagnostic purpose, in the remaining c...

Digestive diseases and sciences, 2002

Microchimerism may be involved in the etiopathogenesis of autoimmune diseases such as scleroderma... more Microchimerism may be involved in the etiopathogenesis of autoimmune diseases such as scleroderma. Primary biliary cirrhosis (PBC) shares some features with scleroderma, including a female predominance and a histologic picture reminiscent of chronic graft-versus-host disease. Our aim was to detect Y-chromosome-specific sequences as a marker for microchimerism in liver tissue of female patients with PBC. Liver biopsies of 105 female patients were investigated (28 patients with primary biliary cirrhosis, 25 patients with chronic hepatitis C, 6 patients with chronic hepatitis B, 9 with autoimmune hepatitis, and 37 patients with other liver diseases) by a sensitive Y-chromosome-specific polymerase chain reaction and/or fluorescence in situ hybridization (FISH) technique for the detection of the Y chromosome on a single cell level. In the liver of 9 (8.6%) female patients Y-chromosome-specific sequences were detected by PCR. Five of the patients had PBC as underlying disease, 2 had chron...

The American Journal of Gastroenterology, 1999

We investigated the prevalence of hepatitis G-RNA (GBV-C/HGV-RNA), a recently cloned new flavivir... more We investigated the prevalence of hepatitis G-RNA (GBV-C/HGV-RNA), a recently cloned new flavivirus, and of antibodies to the envelope 2 antigen (anti-E2), a marker of past infection, in patients with autoimmune hepatitis, and compared it with the prevalence in patients with chronic viral hepatitis and healthy control individuals. Sera of 63 patients with autoimmune hepatitis were studied for the presence of GBV-C/HGV-RNA by reverse-transcription polymerase chain reaction and for anti-E2 by enzyme-linked immunosorbent assay. GBV-C/HGV genotypes were determined by genome sequencing. Patients with autoimmune hepatitis had a similar high prevalence of GBV-C/HGV-RNA and anti-E2 antibodies as patients with chronic viral hepatitis B or C. GBV-C/HGV-RNA was found significantly more often in patients with autoimmune hepatitis (11%, p = 0.045), hepatitis B (16%, p = 0.004), or hepatitis C (21%, p = 0.001) than in healthy controls (2%). The prevalence of anti-E2 antibodies in patients with autoimmune hepatitis was not different from healthy controls (17% vs 13%, NS). The various subtypes of autoimmune hepatitis had similar prevalence rates of GBV-C/HGV-RNA as patients with liver-kidney microsomal antibody-positive hepatitis C. All of our anti-E2+ (GBV-C/HGV-RNA-) patients were positive for anti-smooth-muscle antibody, whereas only 29% of GBV-C/HGV-RNA+ (anti-E2-) patients were positive (p = 0.025). All seven of the GBV-C/HGV-RNA+ patients with autoimmune hepatitis had genotype 2a, which is also the most prevalent genotype in our region. The prevalence of GBV-C/HGV-RNA is significantly increased in patients with autoimmune hepatitis, compared with healthy controls, and is similar to the increased prevalence seen in chronic hepatitis B or C patients. Anti-E2 positivity was associated with antibodies against smooth-muscle antigen in all cases. All GBV-C/HGV+ autoimmune hepatitis patients were infected with genotype 2a.

The American Journal of Gastroenterology, 2003

OBJECTIVE: Hepatocellular carcinoma (HCC) is a late consequence of severe liver disease. Patients... more OBJECTIVE: Hepatocellular carcinoma (HCC) is a late consequence of severe liver disease. Patients with genetic hemochromatosis may be at risk for HCC, but limited information is available on the relationship of HCC and heterozygosity for the HFE gene mutations. METHODS: HFE mutations (C282Y and H63D) were assessed in 162 consecutive patients (131 men/31 women) with HCC. A total of 159 patients had cirrhosis. The most common etiologies of cirrhosis were chronic viral hepatitis (hepatitis C 39%, hepatitis B 9%) and alcoholic liver disease (36%). RESULTS: Five patients were C282Y homozygotes, four C282Y/H63D compound heterozygotes, and three H63D homozygotes. The C282Y and H63D allele frequencies in HCC were 8.3 (95% confidence limit ϭ 5.3-11.3) and 11.1 (7.8-14.6), respectively, and not different from previously published data in healthy subjects or patients with chronic hepatitis C in Austria. Furthermore, there was no difference in the age at diagnosis in patients with or without HFE gene mutations. C282Y homozygotes had a 19-fold increased risk to develop HCC. In contrast, all other HFE allele constellations were not associated with such a risk. CONCLUSIONS: Except for C282Y homozygotes, HFE gene mutations do not increase the risk to develop HCC in patients with cirrhosis.

Wiener Medizinische Wochenschrift, 2006

Ausschluss von trisialo-transferrin von der Carbohydrate-Deficient-Transferrin-Messung Zusammenfa... more Ausschluss von trisialo-transferrin von der Carbohydrate-Deficient-Transferrin-Messung Zusammenfassung. Hintergrund: Biologische Marker des chron. Alkoholkonsums wie MCV, GGT oder Carbohydrate Deficient transferrin (CDT) sind klinisch hilfreich, jedoch nicht absolut aussagekräftig. Besonders bei Patienten mit bereits etablierter Lebererkrankung wäre ein verlässlicher Marker des chronischen Alkoholkonsums zum Erkennen der zu Grunde liegenden Krankheitsätiologie höchst wünschenswert. Die Messung des CDT wurde durch eine verbesserte ELISA Version, die Asialo-, Monosialo-und Disialo-Transferrin misst, nicht jedoch das Trisialo-Transferrin inkludiert weiterentwickelt und verspricht höhere Sensitivität und Spezifität in der Aufdeckung eines kürzlich entdeckten Alkoholkonsums. Ziel: Studienziel war es bei Patienten mit Lebererkrankung Sensitivität, Spezifität, positiv und negativ prädiktiven Wert des CDT-TRISIALO (-) mit dem CDT-TRISIALO (+) zu vergleichen. Patienten und Methoden: Die Studienpopulation bestand aus 110 konsekutiven Patienten (männlich: n = 80 [72,7 %], weiblich: n = 30 [27,3 %]) mit Lebererkrankung der folgenden ätiologischen Kategorien: chronischer Alkoholkonsum (n = 51 [46,4 %], chronische Virushepatitis (n = 33 [30,0 %], Hämochromatose (n = 4 [3,6 %]), mechanische Cholestase (n = 17 [15,5 %]) und andere Lebererkrankungen (n = 5). 30 Patienten hatten keine Leberzirrhose, bei der Mehrheit (n = 80) fand sich eine Leberzirrhose. Ergebnisse: Bei Patienten mit Lebererkrankung hatte der CDT-TRISIALO (-) Test beim publizierten Cutoff Wert von 2,6 % eine Sensitivität von 72,7 % und eine Spezifität von 58,1 % für rezent zurückliegenden Alkoholkonsum. Der positiv prädikitve Wert war 34,0 % und der negativ prädiktive Wert 87,8 %. Der CDT TRISIALO (+) Test erreichte bei einem empfohlenen Cutoff Level von 4,7 % mit 73,3 % und 49,3 % ähnliche Sensitivitäts-und Spezifitätswerte. Positiver und negativer prädiktiver Wert lagen bei 30,9 % bzw. 88,1 % Sowohl CDT-TRSIALO (+) als auch CDT-TRSISIALO (-) korrelierten positiv mit dem Child-Pugh Leberzirrhose Stadium. Zusammenfassung: Der modifizierte Carbohydrate Deficient Transferrin (CDT) Test (CDT-TRISIALO (-)) zeigte in einer Gruppe von Patienten mit Lebererkrankung keinen eindeutigen Vorteil gegenüber dem etablierten CDT-TRISIALO (+) Test. In einer Population von Patienten mit Lebererkrankungen kann ein normales Ergebnis des sowohl CDT-TRISIALO (+) als auch des CDT-TRISIALO (-) Tests als Argument für den Ausschluss eines rezenten Alkoholgebrauchs gelten. Schlüsselwörter: CDT (Carbohydrate Deficient Transferrin), chronischer Alkoholkonsum, chronische Lebererkrankung. Summary. Background: Biological markers for chronic alcohol consumption like MCV or γGT or carbohydrate deficient transferrin (CDT) are useful, but far from being perfect. In patients with liver disease a reliable marker for chronic alcohol consumption as the underlying etiology is highly needed. Recently, a new ELISA based version of the carbohydrate-deficient-transferrin (CDT-TRISIA-LO (-)) assay has been developed, which measures asialo-, monosialo-and disialo transferrin, but excludes trisialo-transferrin; that modification suggests higher sensitivity and specificity in detecting recent alcohol consumption in patients.