Hospital Oberndorf

Oberndorf bei Salzburg, Austria

Hospital Oberndorf

Oberndorf bei Salzburg, Austria
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Beinhardt S.,Medical University of Vienna | Aberle J.H.,Medical University of Vienna | Strasser M.,Paracelsus Medical University | Duliclakovic E.,Wilhelminenspital | And 15 more authors.
Gastroenterology | Year: 2012

Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC). We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls). The IL28B SNPs rs12979860 and rs8099917 were detected using real-time polymerase chain reaction; serum concentrations of IP-10 were measured by enzyme-linked immunosorbent assays of 62 patients with AHC. Hepatitis C virus was cleared spontaneously from 59 patients (49.2%). The IL28B rs12979860 C/C genotype was more frequent among patients with AHC than controls (62.5% vs 39.6%; P <.001) and among patients with spontaneous clearance than those without (74.6% vs 51.7%; P =.02) (positive predictive value, 60.3%). Patients with IL28B rs12979860 C/C more frequently developed jaundice (53.2% vs 27.6%; P =.022) than carriers of the T allele. The median level of IP-10 was lower among patients with AHC and spontaneous clearance (764 [1132470] pg/mL) than those without spontaneous clearance (1481 [1414412] pg/mL; P =.006). Based on receiver operating characteristic analysis, 540 pg/mL IP-10 was set as the cutoff for patients most likely to have spontaneous clearance (positive predictive value, 71.4%; negative predictive value, 65.9%). Including data on IP-10 levels increased the ability of the IL28B rs12979860 C/C to identify patients most likely to have spontaneous clearance (83% of those who had an IP-10 level <540 pg/mL and 32% who had an IP-10 level >540 pg/mL) (P <.01). The combination of serum level of IP-10 and SNPs in IL28B can identify patients with AHC who are most likely to undergo spontaneous clearance and those in need of early antiviral therapy. © 2012 AGA Institute.

Beinhardt S.,Medical University of Vienna | Payer B.A.,Medical University of Vienna | Datz C.,Hospital Oberndorf | Strasser M.,Paracelsus Medical University | And 12 more authors.
Journal of Hepatology | Year: 2013

Background & Aims IL28B polymorphisms, jaundice, decline in HCV-RNA, IP-10, and gender have been proposed to be indicative of spontaneous clearance of acute hepatitis C virus infection. The aim of this study was to define a score enabling the discrimination of patients with spontaneous clearance of HCV from those with development of viral persistence and need for early antiviral treatment. Methods 136 patients (74 male; 35 ± 15 years) were analyzed. From variables predictive of spontaneous clearance, calculated by univariate analysis, three scores were built. Analogous cut-offs were evaluated by computing area under the receiver operating characteristic curves. Candidate variables and cut-offs were: (I) presence of IL28B C/C (p = 0.027), (II) age (p = 0.031; cut-off: 35 years), (III) peak-bilirubin (p = 0.018; cut-off: 6 mg/dl), (IV) HCV-RNA decline within 4 weeks (p <0.001;cut-off: >2.5 log), (V) serum IP-10 (p = 0.003; cut-off: 546 pg/ml), (VI) presence of CD4(+) Th1 cells (p = 0.024). Each variable was allocated to 0 or 1 point, an HCV-RNA decline of ≥1 log10 but <2.5 log10 to 1 point, a decline of ≥2.5 log10 to 2 points. Three scores were evaluated (Score 1: I-IV; Score 2: I-V; Score 3: I-VI). Results A cut-off of ≥3 points out of 5 in Score 1 (AUROC: 0.82; DeLong 95% CI: 0.76-0.93) predicted spontaneous clearance with a sensitivity of 71% (95% CI: 0.53-0.86) and specificity of 87% (95% CI: 0.73-0.95). PPV and NPV were 79% and 82%. Corresponding findings for Score 2 including IP-10 (AUROC: 0.93; DeLong 95% CI: 0.86-0.93) at a cut-off of ≥4 were: sensitivity 81%, specificity 95% (PPV: 100%; NPV: 77%). A cut-off of ≥5 in Score 3 (AUROC: 0.98; DeLong 95% CI: 0.95-1.0) predicted spontaneous resolution with a sensitivity of 75% and specificity of 100% (PPV: 100%; NPV: 88%). Conclusions The scores enable a reliable discrimination between AHC-patients with high potential for spontaneous clearance from candidates for early therapeutic intervention due to marginal chance of spontaneous resolution.

Scherzer T.-M.,Medical University of Vienna | Stattermayer A.F.,Medical University of Vienna | Stauber R.,Medical University of Graz | Maieron A.,Elisabethinen Hospital | And 9 more authors.
Journal of Hepatology | Year: 2013

Background & Aims Single nucleotide polymorphisms (SNPs) in the inosine triphosphate pyrophosphatase (ITPA) gene protect patients from ribavirin induced anemia. To investigate other possible protective cofactors, gender differences were analyzed in patients with HCV genotype 1. Methods Hemoglobin levels at baseline (Hb0) and the decline after 4 weeks of treatment (HbΔ4) were analyzed in 308 chronic hepatitis C patients participating in 5 Austrian trials (n = 308, age 43.9 ± 11.1, male:185, female:123, BMI 25.3 ± 3.9, no cirrhosis: n = 259, liver cirrhosis: n = 49). All patients were treated with 180 μg peginterferon-alpha 2a and ribavirin [1000-1200 mg/d; females: mean (95% CI) 15.8 mg/kg (15.4-16.2); males 14.3 (14.1-14.5); p <0.001]. The SNPs rs6051702, rs1127354, rs7270101 and IL28B rs12979860 were analyzed by the StepOnePlus Real time PCR System. Results 188 were major alleles homozygotes; 95 (30.8%) carried the minor allele (C) of rs6051702, 47 (15.3%) of rs1127354 (A), and 69 (22.4%) of rs7270101 (C). The overall Hb0 was 14.8 g/dl (14.6-14.9) [mean (95%CI); females 13.7 (13.5-13.9); males 15.5; 15.3-15.6; p <0.001]. The overall HbΔ4 was greater in major allele homozygotes [2.8 g/dl (2.6-3.0)] than in minor allele carriers [1.6 (1.4-1.9); p <0.001]. Irrespective of the ITPA genotypes HbΔ4 was smaller in female [2.0 (1.7-2.2)] than in male patients [2.6 (2.4-2.8); p <0.001] and among females in premenopausal [1.5 (1.3-1.8)] than in postmenopausal patients [2.7 (2.3-3.1); p <0.001]. Conclusions Irrespective of the protective effect of ITPA mutations, premenopausal females less likely develop ribavirin induced anemia.

Beinhardt S.,Medical University of Vienna | Leiss W.,University of Bern | Stattermayer A.F.,Medical University of Vienna | Graziadei I.,Innsbruck Medical University | And 9 more authors.
Clinical Gastroenterology and Hepatology | Year: 2014

Background & Aims: Wilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in a well-characterized Austrian cohort of patients with Wilson disease. Methods: We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes. For 53 patients lost during the follow-up period, those that died and reasons for their death were identified from the Austrian death registry. Results: The mean observation period was 14.8 ± 11.4 years (range, 0.5-52.0 years), resulting in 3116 patient-years. Of the patients, 61% presented with hepatic disease, 27% with neurologic symptoms, and 10% were diagnosed by family screening at presymptomatic stages. Patients with a hepatic presentation were diagnosed younger (21.2 ± 12.0 years) than patients with neurologic disease (28.8 ± 12.0; P < .001). In 2% of patients, neither symptoms nor onset of symptoms could be determined with certainty. Most patients stabilized (35%) or improved on chelation therapy (26% fully recovered, 24% improved), but 15% deteriorated; 8% required a liver transplant, and 7.4% died within the observation period (71% of deaths were related to Wilson disease). A lower proportion of patients with Wilson disease survived for 20 years (92%) than healthy Austrians (97%), adjusted for age and sex (P = .03). Cirrhosis at diagnosis was the best predictor of death (odds ratio, 6.8; 95% confidence interval, 1.5-31.03; P = .013) and need for a liver transplant (odds ratio, 07; 95% confidence interval, 0.016-0.307; P < .001). Only 84% of patients with cirrhosis survived 20 years after diagnosis (compared with healthy Austrians, P =008). Conclusion: Overall, patients who receive adequate care for Wilson disease have a good long-term prognosis. However, cirrhosis increases the risk of death and liver disease. Early diagnosis, at a precirrhotic stage, might increase survival times and reduce the need for a liver transplant. © 2014 AGA Institute.

Husar-Memmer E.,Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of and Trauma Center Meidl | Stadlmayr A.,Hospital Oberndorf | Datz C.,Hospital Oberndorf | Zwerina J.,Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of and Trauma Center Meidl
Current Rheumatology Reports | Year: 2014

Hereditary hemochromatosis is a frequent disease in Caucasian populations. It leads to progressive iron overload in a variety of organs. The most common cause is the C282Y homozygous mutation in the HFE gene. The classical triad of skin hyperpigmentation, diabetes, and liver cirrhosis is nowadays rare but musculoskeletal symptoms are common in HFE-related hemochromatosis. Typically the second and third metacarpophalangeal joints, and the wrist, hip, and ankle joints are affected. Clinical symptoms include osteoarthritis-like symptoms, pseudogout attacks, and synovitis sometimes resembling rheumatoid arthritis. Radiographs show degenerative changes with joint space narrowing, osteophytes, and subchondral cysts. Chondrocalcinosis in the wrist and knee joints is seen in up to 50 % of patients. Although most other organ manifestations regress during phlebotomy, musculoskeletal symptoms often persist or even become worse. Importantly, patients are at an increased risk of severe large-joint arthritis necessitating joint replacement surgery. Therefore, future research should focus on the pathogenesis and treatment options for HH arthropathy. © 2013 Springer Science+Business Media New York.

Dulic-Lakovic E.,Wilhelminenspital | Dulic M.,Wilhelminenspital | Hubner D.,Klinikum Wels | Fuchssteiner H.,Elisabethinen Hospital | And 11 more authors.
Gastrointestinal Endoscopy | Year: 2011

Background: Dieulafoy lesions consist of aberrant submucosal arteries, which can cause severe GI bleeding. The predominant location of Dieulafoy lesions is the upper GI tract. Objective: To our best knowledge, this is the first systematic study on the frequency of bleeding from Dieulafoy lesions in the small bowel and the efficacy of enteroscopic therapy regarding primary hemostasis and long-term follow-up. Design: Multicenter, retrospective, observational study. Setting: Nine Austrian centers doing double-balloon enteroscopy or single-balloon enteroscopy. Patients: This study involved 284 consecutive patients who were referred for double-balloon enteroscopy or single-balloon enteroscopy because of suspicion of mid-GI bleeding. Intervention: A total of 317 double-balloon enteroscopy and 78 single-balloon enteroscopy procedures were performed in 284 patients with suspected mid-GI bleeding. Main Outcome Measurements: Demographic, clinical, procedural, and outcome data were collected. Results: A Dieulafoy lesion in the small bowel was identified as the source of mid-GI bleeding in 3.5% of patients, with a mean of 1.5 enteroscopy sessions required per diagnosis. In 9 cases the Dieulafoy lesion was found by enteroscopy from an oral approach, and in 1 patient the lesion was found by an anal approach. In all patients primary endoscopic hemostasis was successful. Eight of 10 patients were free from rebleeding episodes (median follow-up 14.5 months, interquartile range 10.0-17.5 months). In 2 of 10 patients, rebleeding occurred, and a surgical intervention was necessary. Limitations: Retrospective study. Conclusion: Bleeding from Dieulafoy lesions of the small bowel seems to occur more frequently than previously estimated. Most of these lesions are located in the proximal jejunum and can be managed successfully by enteroscopy. After successful endoscopic hemostasis, rebleeding episodes occur in only 20% of patients. © 2011 American Society for Gastrointestinal Endoscopy.

Sahinbegovic E.,Friedrich - Alexander - University, Erlangen - Nuremberg | Dallos T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Dallos T.,Comenius University | Aigner E.,Hospital Oberndorf | And 13 more authors.
Arthritis and Rheumatism | Year: 2010

Objective. To determine the prevalence, clinical picture, and disease burden of arthritis in patients with hereditary hemochromatosis. Methods. In this cross-sectional observational study of 199 patients with hemochromatosis and iron overload, demographic and disease-specific variables, genotype, and organ involvement were recorded. The prevalence, intensity, and localization of joint pain were assessed, and a complete rheumatologic investigation was performed. Radiographs of the hands, knees, and ankles were scored for joint space narrowing, erosions, osteophytes, and chondrocalcinosis. In addition, the number and type of joint replacement surgeries were recorded. Results. Joint pain was reported by 72.4% of the patients. Their mean ± SD age at the time of the initial joint symptoms was 45.8 ± 13.2 years. If joint pain was present, it preceded the diagnosis of hemochromatosis by a mean ± SD of 9.0 ± 10.7 years. Bony enlargement was observed in 65.8% of the patients, whereas synovitis was less common (13.6%). Joint space narrowing and osteophytes as well as chondrocalcinosis of the wrist and knee joints were frequent radiographic features of hemochromatosis. Joint replacement surgery was common, with 32 patients (16.1%) undergoing total joint replacement surgery due to severe OA. The mean ± SD age of these patients was 58.3 ± 10.4 years at time of joint replacement surgery. Female sex, metacarpophalangeal joint involvement, and the presence of chondrocalcinosis were associated with a higher risk of early joint failure (i.e., the need for joint replacement surgery). Conclusion. Arthritis is a frequent, early, and severe symptom of hemochromatosis. Disease is not confined to involvement of the metacarpophalangeal joints and often leads to severe damage requiring the replacement of joints. Copyright © 2010 by the American College of Rheumatology.

Nell-Duxneuner V.,Ludwig Boltzmann Research Institute | Axmann R.,Ludwig Boltzmann Research Institute | Husar-Memmer E.,Ludwig Boltzmann Research Institute | Dallos T.,Comenius University | And 9 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objectives: The aim of this study was to assess the role of vascular adhesion molecule 1 (VCAM-1) in patients with hereditary haemochromatosis (HH) with or without arthropathy. Methods: Sera from a large cross-sectional cohort of unselected HH patients (n=147) were obtained and compared to an age-matched and sex-matched control group. Serum levels of VCAM-1 were measured by ELISA and were correlated with clinical measures. Results: VCAM-1 serum levels were elevated in HH patients as compared to matched controls (mean 913±456 vs 654±451 ng/ml, p<0.0001). Within the HH patient group, VCAM-1 levels were much higher in patients with arthropathy and joint replacement surgery. VCAM-1 levels correlated well with radiographic measures of HH arthropathy (r=0.36, p<0.0001). Multivariate regression analysis confirmed a highly significant association of VCAM-1 serum levels and the presence of HH arthropathy, independent from diabetes, body mass index and age. Conclusions: VCAM-1 serum levels emerge as a biomarker for haemochromatosis arthropathy.

Heiland G.R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Aigner E.,Hospital Oberndorf | Dallos T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Dallos T.,Comenius University | And 8 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Background: Hereditary haemochromatosis (HH) is a common autosomal recessive inherited disorder that frequently causes arthritis. The pathophysiology of musculoskeletal involvement is, however, unclear. Objective: To analyse synovial tissue obtained at surgery from patients with HH arthropathy and compare it qualitatively and quantitatively with specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods: Synovial tissue from 15 patients with HH, 20 with RA and 39 with OA was obtained during surgery. A synovitis grading system was used to determine the severity of synovial inflammation. Using immunohistochemistry, synovial neovascularisation and infiltration of macrophages, neutrophils and lymphocytes were quantitatively assessed. Results: Synovitis in HH arthropathy largely resembles OA with mild infiltration of mononuclear cells and lymphocytes, formation of synovial microvessels and a low degree of synovial hyperplasia. While many features of HH arthropathy are reminiscent of OA, macrophage and especially neutrophil invasion is clearly more prominent in HH arthropathy than in primary OA and mimics features of RA. This finding was observed particularly in synovial tissue of HH samples with marked haemosiderin deposition. Discussion: The histological picture of the synovium in HH arthropathy largely resembles a process reminiscent of OA. Neutrophil invasion is, however, markedly increased in HH arthropathy, especially in joints with iron deposition. Accumulation of neutrophils may be crucial for the production of matrix enzymes, which enables cartilage degradation and more rapidly progressive articular damage.

PubMed | University of Zürich, Paracelsus Medical University and Hospital Oberndorf
Type: Journal Article | Journal: The American journal of gastroenterology | Year: 2016

Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity; however, 5-8% of lean subjects also have evidence of NAFLD. We aimed to investigate clinical, genetic, metabolic and lifestyle characteristics in lean Caucasian subjects with NAFLD.Data from 187 subjects allocated to one of the three groups according to body mass index (BMI) and hepatic steatosis on ultrasound were obtained: lean healthy (BMI25kg/mLean NAFLD subjects had fasting insulin concentrations similar to lean healthy subjects but had markedly impaired glucose tolerance. Lean NAFLD subjects had a higher rate of the mutant PNPLA3 CG/GG variant compared to lean controls (P=0.007). Serum adiponectin concentrations were decreased in both NAFLD groups compared to controls (P<0.001 for both groups) The metabolomics study revealed a potential role for various lysophosphatidylcholines (lyso-PC C18:0, lyso-PC C17:0) and phosphatidylcholines (PCaa C36:3; false discovery rate (FDR)-corrected P-value<0.001) as well as lysine, tyrosine, and valine (FDR<0.001).Lean subjects with evidence of NAFLD have clinically relevant impaired glucose tolerance, low adiponectin concentrations and a distinct metabolite profile with an increased rate of PNPLA3 risk allele carriage.

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