Heidemarie Holzmann

Medical University of Vienna, Wien, Vienna, Austria

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Publications (100)502.63 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and aims: The severity of acute viral hepatitis, which may be caused by several distinct viruses, varies among individual patients. In rare cases severe hepatic injury with sudden loss of liver function may occur, which is clinically indicated by the occurrence of coagulopathy or encephalopathy. Since the molecular mechanisms of this liver injury are largely unknown, we investigated extracellular micro RNA (miRNA) profiles in 54 patients acutely infected with one of four different hepatotropic viruses, in order to identify those miRNAs which indicate severe viral hepatitis associated with coagulopathy. Methods: First, the profile of miRNAs was extensively analyzed using a microarray-based approach in highly characterized 24 patients, matched in terms of sex, age and level of liver enzymes, as well as in 3 healthy controls. The cohort included samples from 18 patients with moderate and 6 individuals with severe hepatitis, indicated by abnormal prothrombin time and higher alanine aminotransferase and bilirubin levels. miRNAs found to upregulated in severe hepatitis were then quantified by Real Time PCR in the expanded cohort of 54 patients RESULTS: Comprehensive microarray-based miRNA profiling identified upregulation of mir-106a, mir-122 and mir197 in patients with severe acute viral hepatitis with coagulopathy, as compared to patients who did not develop coagulopathy. mir-106a, mir-122 and mir-197 were then proven to be significantly upregulated in patients with severe acute viral hepatitis by quantitative real-time PCR (p<0.01, Mann Whitney U-test). Conclusions: mir-106a, mir-122 and mir-197 could be potential markers for severe acute viral hepatitis associated with coagulopathy. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 09/2015; DOI:10.1111/liv.12961 · 4.85 Impact Factor
  • Zeitschrift für Gastroenterologie 05/2015; 53(05). DOI:10.1055/s-0035-1551763 · 1.05 Impact Factor
  • F X Heinz · K. Stiasny · H. Holzmann · M. Kundi · W. Six · M. Wenk · W. Kainz · A. Essl · C. Kunz
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    ABSTRACT: Human infections with tick-borne encephalitis (TBE) virus are a public health concern in certain regions of Europe, central and eastern Asia. Expansions of endemic areas and increased incidences have been associated with different factors including ecological changes supporting tick reproduction, socioeconomic changes increasing human outdoor activities and climatic changes favouring virus circulation in natural foci. Austria is among the most strongly affected countries in Central Europe, but the annual number of cases has strongly declined due to vaccination. Here, we have analysed changes of the incidence of TBE in the unvaccinated population of all federal states of Austria over a period of 42 years. The overall incidence in Austria has remained constant, but new strongly affected endemic regions have emerged in alpine valleys in the west of Austria. In parallel, the incidence in low-land regions in the north-east of the country is decreasing. There is no evidence for a shift to higher altitudes of infection sites in the traditional TBE zones, but the average altitudes of some newly established endemic areas in the west are significantly higher. Our analyses underscore the focal nature of TBE endemic areas and the potential of TBE virus to emerge in previously unaffected regions. © 2015, European Centre for Disease Prevention and Control (ECDC). All rights reserved.
    Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 04/2015; 20(13). DOI:10.2807/1560-7917.ES2015.20.13.21077 · 5.72 Impact Factor
  • Zeitschrift für Gastroenterologie 01/2015; 53(01). DOI:10.1055/s-0034-1397231 · 1.05 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S303-S304. DOI:10.1016/S0168-8278(14)60866-7 · 11.34 Impact Factor
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    ABSTRACT: Hepatitis E virus (HEV) is a small RNA virus and the infectious agent of hepatitis E that occurs worldwide either as epidemics in Asia caused by genotype 1 and 2 or as sporadic disease in industrialized countries induced by genotype 3 and 4. The frequency might be underestimated in central Europe as a cause of acute hepatitis. Therefore, we analyzed on liver biopsies, if cases of acute hepatitis with clinically unknown or obscure diagnosis were actually caused by the infection with HEV. We included 221 liver biopsies retrieved from the files of the institute of pathology during the years 2000 till 2010 that were taken from patients with acute hepatitis of obscure or doubtful diagnosis. From all biopsies RNA was extracted, prepared, and subjected to RT-PCR with specific primers. Amplified RNA was detected in 7 patients, sequenced and the genotype 3 could be determined in four of the seven of positive specimens from 221 samples. Histopathology of the biopsies revealed a classic acute hepatitis with cholestatic features and in some cases confluent necrosis in zone 3. Histology in a cohort of matched patients was less severe and showed more eosinophils. The analysis of the immune response by subtyping of liver infiltrating lymphocytes showed circumstantial evidence of adaptive immune reaction with CD 8 positive CTLs being the dominant lymphocyte population. In conclusion, in doubtful cases of acute hepatitis of unknown origin, HEV infection should be considered as etiology in central Europe. We demonstrate for the first time that the diagnosis can be made in paraffin-embedded liver biopsies reliably when no serum is available and also the genotype can be determined. The analysis of the immune response by subtyping of liver infiltrating lymphocytes indicates an adaptive mechanism suggesting in analogy with HAV, HBV and HCV that the virus itself is not cytopathic but liver damage is due to immune reaction.
    Frontiers in Physiology 12/2013; 4:351. DOI:10.3389/fphys.2013.00351 · 3.53 Impact Factor
  • Dietmar Schiller · Rainer Schoefl · Heidemarie Holzmann
    Gastroenterology 11/2013; 146(1). DOI:10.1053/j.gastro.2013.09.024 · 16.72 Impact Factor
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    ABSTRACT: In Austria the vaccination coverage among health care workers (HCW) - particularly among hospital personnel - is not sufficient. This is of specific concern, because not only the individual protection but also the prevention of disease transmission of vaccine preventable diseases between HCW and patients needs to be guaranteed. Particularly immunosuppressed patients, who are at higher risk for morbidity and mortality due to certain infections, but cannot be vaccination themselves, must be able to rely on herd protection, i.e. not being infected by surrounding/caring persons.The following publication provides for the first time detailed guidelines for vaccination programs for HCWs in Austria, including personnel within hospitals, medical institutions and laboratories, as well as Medical Universities including students. Moreover, these guidelines are also recommended to medical personnel in outpatient clinics, social service institutions and medical practices.Additionally to the vaccination schedules this publication also includes a chapter on ethical as well as legal background underlying these recommendations.
    Wiener klinische Wochenschrift 11/2013; 126. DOI:10.1007/s00508-013-0461-9 · 0.84 Impact Factor
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    ABSTRACT: IL28B-polymorphisms, jaundice, decline in HCV-RNA, IP-10 and gender have been proposed to be indicative for spontaneous clearance of acute hepatitis C virus infection. Aim of this study was to define a score enabling the discrimination of patients with spontaneous clearance of HCV from those with development to viral persistence and need for early antiviral treatment. 136 patients (male:74;35±15years) were analyzed. From variables predictive for spontaneous clearance, calculated by univariate analysis, three scores were built. Analogous cutoffs were evaluated by computing area under the receiver operating characteristic curves. Candidate variables and cutoffs were: (I)presence of IL28B-C/C (P=0.027), (II)age (P=0.031;cutoff:35years), (III)peak-bilirubin (P=0.018;cutoff:6mg/dl), (IV)HCV-RNA-decline within 4 weeks (P<0.001;cutoff:>2.5log), (V)serum IP-10 (P=0.003;cutoff:546pg/ml), (VI)presence of CD4(+)Th1-cells (P=0.024). Each variable was allocated to 0 or 1 point, an HCV-RNA-decline of ⩾1log(10) but <2.5log(10) 1 point, a decline of ⩾2.5log(10) to 2 points. Three scores were evaluated (Score1:I-IV; Score2:I-V; Score3:I-VI). A cutoff of ⩾3 points out of 5 in Score1 (AUROC:0.82; DeLong95%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 Score2 including IP-10 (AUROC:0.93; DeLong95%CI:0.86-0.93) at a cutoff ⩾4 were: sensitivity 81%, specificity 95% (PPV:100%;NPV:77%). A cutoff of ⩾5 in Score3 (AUROC:0.98; DeLong95%CI:0.95-1.0) predicted spontaneous resolution with a sensitivity of 75% and specificity of 100% (PPV:100%;NPV:88%). 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.
    Journal of Hepatology 07/2013; 59(5). DOI:10.1016/j.jhep.2013.06.028 · 11.34 Impact Factor
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    ABSTRACT: The introduction of direct-acting anti-virals has increased sustained virological response (SVR) rates in chronic hepatitis C genotype 1 infection. At present, data on long-term durability of viral eradication after successful triple therapy are lacking. To evaluate the long-term durability of viral eradication in patients treated with triple therapy, including direct-acting anti-virals. Patients who participated in randomised, controlled trials or an extended access programme of treatment with peginterferon-α2a/ribavirin in combination with a direct-acting anti-viral (telaprevir, danoprevir, faldaprevir, simeprevir, mericitabine, balapiravir) were followed after achieving SVR. The median follow-up after the patients was 21 (range: 7–64) months. One hundred and three patients with chronic hepatitis C genotype 1 infection [f/m: 34/69; GT-1b: 67 GT-1a: 34, GT-4: 2; mean age: 47.6 years (45.5–49.7; 95% CI)] achieving a SVR triple therapy were followed. Two cases of late relapses (2/103, 1.9%; 95% CI: 0.24–6.8) were observed. One patient was cirrhotic, both carried the genotype 1b and completed the prescribed treatment. The relapses occurred 8 and 12 months after cessation of anti-viral treatment. Cloning sequencing revealed identical sequence in both patients. Resistance analysis revealed no presence of viral resistance. Like the SVR after peginterferon-α2/ribavirin combination treatment, HCV eradication after triple therapy remains durable after long-term follow-up.
    Alimentary Pharmacology & Therapeutics 05/2013; 38(2). DOI:10.1111/apt.12350 · 5.73 Impact Factor
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    ABSTRACT: Tick-borne encephalitis (TBE) is a substantial public health problem in many parts of Europe and Asia. To assess the effect of increasing TBE vaccination coverage in Austria, we compared incidence rates over 40 years for highly TBE-endemic countries of central Europe (Czech Republic, Slovenia, and Austria). For all 3 countries we found extensive annual and longer range fluctuations and shifts in distribution of patient ages, suggesting major variations in the complex interplay of factors influencing risk for exposure to TBE virus. The most distinctive effect was found for Austria, where mass vaccination decreased incidence to ≈16% of that of the prevaccination era. Incidence rates remained high for the nonvaccinated population. The vaccine was effective for persons in all age groups. During 2000-2011 in Austria, ≈4,000 cases of TBE were prevented by vaccination.
    Emerging Infectious Diseases 01/2013; 19(1):69-76. DOI:10.3201/eid1901.120458 · 6.75 Impact Factor
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    ABSTRACT: Tick-borne encephalitis (TBE) is an emerging viral zoonosis and is endemic from Japan, China, Mongolia and Russia, to Central Europe and France. There is no specific treatment and TBE can be fatal. The four licensed prophylactic vaccines are produced according to WHO manufacturing requirements. Large clinical trials and postmarketing surveillance demonstrated safety and efficacy of the two European vaccines. The two Russian vaccines showed their effectiveness in daily use, but limited published data are available on controlled clinical trials. Vaccination recommendations in endemic areas vary significantly. In some countries, public vaccination programs are implemented. The WHO has recently issued recommendations on evidence-based use of TBE vaccines. However, more data are needed regarding safety, efficacy and long-term protection after vaccination.
    Expert Review of Vaccines 09/2012; 11(9):1103-1119. DOI:10.1586/erv.12.86 · 4.21 Impact Factor
  • K Stiasny · J H Aberle · V Chmelik · U Karrer · H Holzmann · F X Heinz
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    ABSTRACT: Tick-borne encephalitis (TBE) is the most important arbovirus disease in parts of Europe and Asia. Its laboratory diagnosis depends on the detection of specific IgM antibodies which can be impeded by (1) long-time persistence of IgM antibodies after infection, (2) vaccine-induced IgM antibodies, and (3) cross-reactive IgM antibodies from other flavivirus infections. To assess the extent of interference factors in the serodiagnosis of TBE that might lead to the false positive assignment of a recent infection. We quantified TBE virus-specific IgM and IgG antibodies in sera collected at different time points from cohorts of (1) 61 TBE patients, (2) 131 TBE vaccinees, and (3) 42 patients with recent dengue or West Nile virus infections. All of the TBE patients were IgM- and IgG-positive upon hospitalization and 87% of acute TBE sera had IgM antibody titers of >500 Arbitrary Units (AU). These titers rapidly declined and only 16% of TBE patients had low IgM titers ≥9 months after infection. Vaccine-induced as well as flavivirus cross-reactive IgM antibodies were rarely detectable and of low titer. Most of the potential problems of TBE serodiagnosis can be resolved by the quantification of IgM antibodies in a single serum sample taken upon hospitalization. High IgM values (>500 AU in our assay) are indicative of a recent infection. Lower IgM values, however, may require the analysis of a follow-up sample and/or a specific neutralization assay to exclude the possibilities of IgM persistence, vaccine-induced IgM antibodies or heterologous flavivirus infections.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 03/2012; 54(2):115-20. DOI:10.1016/j.jcv.2012.02.016 · 3.02 Impact Factor
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    ABSTRACT: 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 [113-2470] pg/mL) than those without spontaneous clearance (1481 [141-4412] 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.
    Gastroenterology 01/2012; 142(1):78-85.e2. DOI:10.1053/j.gastro.2011.09.039 · 16.72 Impact Factor
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    ABSTRACT: A polymorphism near the IL28B gene has been shown to be associated with virologic response to antiviral treatment in HCV-infected patients. The predictive value of interferon-gamma inducible protein 10 (IP10) on treatment outcome has been described in HCV patients. Data on combining these predictors in HIV-HCV-coinfected patients are not available. Virologic parameters, IL28B single nucleotide polymorphisms (SNP) and pretreatment serum IP10 were determined in HIV-HCV-coinfected patients having completed antiviral therapy with pegylated interferon/ribavirin. A total of 72 HIV-HCV-coinfected patients were included in the study; 68% had HCV genotype (GT)-1/4 and 32% had HCV GT-2/3 infections. Rapid virologic response (63% vs. 28%; P = 0·023) and sustained virologic response (SVR: 81% vs. 51%; P = 0·008) rates were significantly higher in C/C vs. non-C/C patients. Patients with low pretreatment IP10 levels (< 400 pg/mL) achieved significantly higher SVR rates than patients with high (> 400 pg/mL) IP10 levels (78% vs. 13%; P < 0·0001). C/C SNP and low IP10 levels were associated with higher SVR rates in both patients with GT-1/4 and GT-2/3. The C/C patients with low IP10 achieved SVR rates of 97% compared with SVR rates of 9% in non-C/C patients with high IP10. The IL28B SNP influences rapid viral response, relapse rates and SVR. The combination of IL28B and IP10 represents a predictive model of SVR in HIV-HCV coinfection.
    European Journal of Clinical Investigation 10/2011; 42(6):599-606. DOI:10.1111/j.1365-2362.2011.02623.x · 2.73 Impact Factor
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    ABSTRACT: A new strain of measles virus, D4-Hamburg, was imported from London to Hamburg in December 2008 and subsequently spread to Bulgaria, where an outbreak of >24,300 cases was observed. We analyzed spread of the virus to demonstrate the importance of addressing hard-to-reach communities within the World Health Organization European Region regarding access to medical care and vaccination campaigns. The D4-Hamburg strain appeared during 2009-2011 in Poland, Ireland, Northern Ireland, Austria, Greece, Romania, Turkey, Macedonia, Serbia, Switzerland, and Belgium and was repeatedly reimported to Germany. The strain was present in Europe for >27 months and led to >25,000 cases in 12 countries. Spread of the virus was prevalently but not exclusively associated with travel by persons in the Roma ethnic group; because this travel extends beyond the borders of any European country, measures to prevent the spread of measles should be implemented by the region as a whole.
    Emerging Infectious Diseases 08/2011; 17(8):1396-401. DOI:10.3201/eid1708.101994 · 6.75 Impact Factor
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    ABSTRACT: To determine the proficiency of the Austrian childhood vaccination schedule to induce long lasting seroprotection against vaccine preventable diseases a seroepidemiological study in 348 children between four and eight years of age was conducted. Antibodies against diphtheria, tetanus, pertussis, hepatitis B, measles, mumps and rubella antigens were assessed in children, who had been vaccinated with hexavalent DTaP-HBV-IPV/Hib vaccines at three, four, five months and in the second year of life and/or MMR vaccines in the second year of life at least once, but mostly twice. High seroprotection rates (SPRs) were detected for tetanus (96%) and measles (90%). SPRs regarding diphtheria and mumps were 81% and 72%, respectively. Rubella-SPRs were 68% in females and 58% in males. Hepatitis B-antibody levels ≥10 mIU/mL were present in 52%; antibodies against pertussis were detected in 27% of the children. SPRs for measles and rubella depended on the interval since last vaccination; mumps-antibodies were significantly lower after one MMR-vaccination only. Antibodies against diphtheria, tetanus and pertussis depended on the interval since last vaccination while HBs-antibodies did not. The low levels of antibodies 1-7 years after vaccination against pertussis, rubella and mumps after only one vaccination should be considered when recommending new vaccination schedules.
    Vaccine 05/2011; 29(32):5130-6. DOI:10.1016/j.vaccine.2011.05.046 · 3.62 Impact Factor
  • S. Koppi · P. Faé · G. Hartmann · R. Höftberger · H. Holzmann
    Der Nervenarzt 04/2011; 82(4):506-508. DOI:10.1007/s00115-010-3190-6 · 0.79 Impact Factor

Publication Stats

3k Citations
502.63 Total Impact Points


  • 2006–2013
    • Medical University of Vienna
      • Department of Virology
      Wien, Vienna, Austria
  • 2006–2009
    • Österreichische Agentur für Gesundheit und Ernährungssicherheit
      Wien, Vienna, Austria
  • 1989–2004
    • University of Vienna
      • Institute of Virology
      Wien, Vienna, Austria