Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Prattes, J.
Invasive Aspergillosis in Patients with Underlying Liver Cirrhosis
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2017. pp.
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- Autor*innen der Med Uni Graz:
- Prattes Jürgen
- Betreuer*innen:
- Hönigl Martin
- Krause Robert
- Raggam Reinhard Bernd
- Zollner-Schwetz Ines
- Altmetrics:
- Abstract:
- Background: Invasive aspergillosis (IA) is a life threatening diseases mainly occurring in highly immunocompromised patients. Recent reports, however, raised concerns that besides those “classical” at risk patients, also patients with less severe immunosuppressive diseases may be prone to develop IA. Liver cirrhosis was mentioned as the only relevant underlying disease in several of those reports. Prospective observational data on the prevalence and outcome of IA in patients with liver cirrhosis are, however, lacking up to date. Thus, we performed a single center, prospective observational study to investigate the prevalence and outcome of IA and the performance of serum galactomannan (GM) screening in patients with underlying liver cirrhosis. Methods: From August 2013 to December 2015, 154 consecutive patients admitted to the University Hospital of Graz, Austria with decompensated liver cirrhosis or compensated liver cirrhosis with fever and/or respiratory symptoms were enrolled in this study. All patients were screened for IA twice weekly by serum GM testing and by checking clinical signs and symptoms for IA. Positive serum GM or clinical suspicion for IA triggered work up consisting of high-resolution computed tomography of the chest and in case of pathological findings bronchoscopy and GM testing in bronchoalveolar lavage fluid. IA was classified according to slightly modified 2008 criteria of the European Organization of Research and Treatment of Cancer/Mycoses Study Group. Performance of serum GM screening was analyzed for the overall cohort as well as for patients with respiratory symptoms only and for patients with clinical suspicion of IA only. Results: Of the 154 enrolled patients, 150 were included in the final analysis. Four patients were retrospectively excluded from the study. Reasons were: liver cirrhosis was mentioned as underlying diseases in the emergency department but rejected after clinical work up (n=2), patient died prior to first serum GM screening (n=1), patient was included in the study within an episode of hepatic encephalopathy and refused to give informed consent after clinical improvement (n=1). Two out of 150 patients (1.3%) were diagnosed with probable IA, one patient with possible IA (0.7%) and the remaining 147 (98%) patients had no evidence for IA. Both patients with probable IA had Child-Pugh grade A cirrhosis and were successfully treated with voriconazole under therapeutic drug monitoring and monitoring of liver function tests. Sensitivity of serum GM screening for presence of probable IA in the overall study cohort was 0.5 [95% confidence interval (95% CI) 0.09 – 0.91], specificity 0.97 (95% CI 0.92 – 0.99), negative predictive value 0.99 (95% CI 0.96 – 0.99) and positive predictive value (PPV) 0.17 (95% CI 0.01 – 0.64). PPV was 0.5 (95% CI 0.03 – 0.98) in patients with clinical suspicion of IA. Conclusions: Prevalence of IA in patients with underlying liver cirrhosis was low in this study. Only two patients (1.3%) were diagnosed with probable IA. These two patients, however, could be treated safely and successfully with voriconazole. Additionally, universal screening of patients with liver cirrhosis by using the serum GM antigen assay was associated with low PPVs due to low pretest probability of the disease. A more targeted approach, for example only using serum GM testing in patients with clinical suspicion for IA, seems to be more appropriate for clinical routine.