Reviewer's report 
 Invasive Pulmonary Aspergillosis in Patients with decompensated cirrhosis : case series Title: 
 1  13 June 2006 Version: Date: 
 koenraad H vandewoude Reviewer: 
Reviewer's report: 
General 
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Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. In all the three cases described, an exposure to corticosteroid therapy is described. Steroid exposure is 
an important risk factor for the development of invasive aspergillosis. In the discussion, it should be stressed that steroid exposure could have played an role in the development of invasive pulmonary 
aspergillosis. It can be speculated that in critically ill patients, the threshold dose for developing this infection 
is lower than in other patients; even stress doses as now routinely used in septic shock may represent a risk 
factor 1 2. Hence, it may be unclear if liver failure, or the combination of liver failure and steroid exposure, 
may have contributed to the infection. 
2. Since all patients died, it would be of interest to know if the clinical suspicion of aspergillosis was 
confirmed by necropsy. We agree that it is difficult to use the EORTC/MSGT criteria for invasive fungal 
infections in patients without malignancy. The authors have made the diagnosis of invasive pulmonary aspergillosis, based on microbiological data and atypical radiological findings. Hence, it should be stressed 
that this diagnosis is not proven in all three cases. However, we agree that the findings are clinically 
relevant and that an adapted clinical algorithm should be used for diagnostic and therapeutic decision making in this type of patients3. 
3.It would be appropriate to describe the patient characteristics more in depth, with APACHE or SAPS 
score, and severity of organ derangements. It seems that these 3 patients were severely ill and that the expected mortality was very high. 
Conclusion: 
Rewriting of the case histories is mandatory, since the diagnosis of proven aspergillosis is not evident (no 
tissue biopsy, no culture of normally sterile site). Discussion should be adapted, highlighting the 
combination of risk factors present in these patients (steroid exposure, liver failure, previous lung disease 
and lung structural damage due to pneumonia and ARDS). 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of limited interest Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 Invasive Pulmonary Aspergillosis in Patients with decompensated cirrhosis : case series Title: 
 1  13 June 2006 Version: Date: 
 koenraad H vandewoude Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. In all the three cases described, an exposure to corticosteroid therapy is described. Steroid exposure is 
an important risk factor for the development of invasive aspergillosis. In the discussion, it should be stressed that steroid exposure could have played an role in the development of invasive pulmonary 
aspergillosis. It can be speculated that in critically ill patients, the threshold dose for developing this infection 
is lower than in other patients; even stress doses as now routinely used in septic shock may represent a risk 
factor 1 2. Hence, it may be unclear if liver failure, or the combination of liver failure and steroid exposure, 
may have contributed to the infection. 
2. Since all patients died, it would be of interest to know if the clinical suspicion of aspergillosis was 
confirmed by necropsy. We agree that it is difficult to use the EORTC/MSGT criteria for invasive fungal 
infections in patients without malignancy. The authors have made the diagnosis of invasive pulmonary aspergillosis, based on microbiological data and atypical radiological findings. Hence, it should be stressed 
that this diagnosis is not proven in all three cases. However, we agree that the findings are clinically 
relevant and that an adapted clinical algorithm should be used for diagnostic and therapeutic decision making in this type of patients3. 
3.It would be appropriate to describe the patient characteristics more in depth, with APACHE or SAPS 
score, and severity of organ derangements. It seems that these 3 patients were severely ill and that the expected mortality was very high. 
Conclusion: 
Rewriting of the case histories is mandatory, since the diagnosis of proven aspergillosis is not evident (no 
tissue biopsy, no culture of normally sterile site). Discussion should be adapted, highlighting the 
combination of risk factors present in these patients (steroid exposure, liver failure, previous lung disease 
and lung structural damage due to pneumonia and ARDS). 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of limited interest Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 Invasive Pulmonary Aspergillosis in Patients with decompensated cirrhosis : case series Title: 
 1  13 June 2006 Version: Date: 
 koenraad H vandewoude Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. In all the three cases described, an exposure to corticosteroid therapy is described. Steroid exposure is 
an important risk factor for the development of invasive aspergillosis. In the discussion, it should be stressed that steroid exposure could have played an role in the development of invasive pulmonary 
aspergillosis. It can be speculated that in critically ill patients, the threshold dose for developing this infection 
is lower than in other patients; even stress doses as now routinely used in septic shock may represent a risk 
factor 1 2. Hence, it may be unclear if liver failure, or the combination of liver failure and steroid exposure, 
may have contributed to the infection. 
2. Since all patients died, it would be of interest to know if the clinical suspicion of aspergillosis was 
confirmed by necropsy. We agree that it is difficult to use the EORTC/MSGT criteria for invasive fungal 
infections in patients without malignancy. The authors have made the diagnosis of invasive pulmonary aspergillosis, based on microbiological data and atypical radiological findings. Hence, it should be stressed 
that this diagnosis is not proven in all three cases. However, we agree that the findings are clinically 
relevant and that an adapted clinical algorithm should be used for diagnostic and therapeutic decision making in this type of patients3. 
3.It would be appropriate to describe the patient characteristics more in depth, with APACHE or SAPS 
score, and severity of organ derangements. It seems that these 3 patients were severely ill and that the expected mortality was very high. 
Conclusion: 
Rewriting of the case histories is mandatory, since the diagnosis of proven aspergillosis is not evident (no 
tissue biopsy, no culture of normally sterile site). Discussion should be adapted, highlighting the 
combination of risk factors present in these patients (steroid exposure, liver failure, previous lung disease 
and lung structural damage due to pneumonia and ARDS). 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of limited interest Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
assistant