Reviewer ’s report  
 
Title: Clinical characteri stics, CT Signs, and Patholo gical Findings of Pyrrolizidine 
Alkaloidsinduced Sinusoidal Obstructive Syndrome: a retrospective study  
 
Version: 0 Date: 15 Oct 2019  
 
Reviewer: David Kleiner  
 
Reviewer's report:  
 
This paper describes a cohort of patients who developed sinusoidal obstruction syndrome (SOS) 
from exposure to pyrrolizidine alkaloids.  Findings are compared to patients with Budd -Chiari 
syndrome and a mouse model of SOS.  Much of the discussion seems to be a summary of the 
results.  Pyrrolizidine alkaloid associated injury has been described before and it would be worth 
comparing this cohort to previous described case series to highlight similarities and differences 
in clinical presentation, imaging finding and histology.  
 
 
Specific com ments  
 
1. Results, p. 10, Clinical presentation.  The authors describe the clinical and associated 
laboratory findings at the time of presentation, but it would also be important to provide details 
of disease evolution.  What was the time course of signs of  injury?  How long did it take patients 
to recover and for laboratory tests to return to normal?  How many patients died?  Were there 
any long -term sequelae in survivors?  
 
 
2. Results, p. 11, line 15, "Further study…" How did the outcome vary between the pat ients in 
the different categories of SOS injury?  
 
 
3. Results, p. 13, Histology.  In stem -cell transplant related SOS, there is usually a component of 
veno -occlusive change, with partial to complete occlusion of small hepatic veins by loose 
collagen and cell s.  Were veno -occlusive changes seen in any of the biopsies?  If not, then that 
would be a significant diagnostic difference between the SOS seen in these two clinical 
situations.  
 
 
4. Discussion, p. 15, line 6.  "…soaked in liquid…"  This is unclear.  Does this mean that the 
patients are preparing tea from these plants?  How do patients get these plants?  Are they 
harvested by the patients themselves or are they included as components of traditional 
medicines? Or both?  
 
 
5. Discussion, p. 19, line 14.  The aut hors note that part of the public education campaign in 
China is to increase awareness of using the PA -containing plants only under the guidance of a 
physician or pharmacist.  Is there any legitimate medicinal use of these plants and if so, for what 
condit ions are they prescribed?  
 
 
6. Figure 3B, 2nd panel.  Rather than depicting a relatively normal portal area from this case, it 
would be better to have a high magnification (400x) photo of the sinusoids near the central vein, 
similar to the 2nd panel of Figur e 3A.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the auth ors. 
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an a dditional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
 
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in  the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my  report to the authors and, if the manuscript is accepted f or publication, my nam ed report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access C reative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Clinical characteri stics, CT Signs, and Patholo gical Findings of Pyrrolizidine 
Alkaloidsinduced Sinusoidal Obstructive Syndrome: a retrospective study  
 
Version: 0 Date: 15 Oct 2019  
 
Reviewer: David Kleiner  
 
Reviewer's report:  
 
This paper describes a cohort of patients who developed sinusoidal obstruction syndrome (SOS) 
from exposure to pyrrolizidine alkaloids.  Findings are compared to patients with Budd -Chiari 
syndrome and a mouse model of SOS.  Much of the discussion seems to be a summary of the 
results.  Pyrrolizidine alkaloid associated injury has been described before and it would be worth 
comparing this cohort to previous described case series to highlight similarities and differences 
in clinical presentation, imaging finding and histology.  
 
 
Specific com ments  
 
1. Results, p. 10, Clinical presentation.  The authors describe the clinical and associated 
laboratory findings at the time of presentation, but it would also be important to provide details 
of disease evolution.  What was the time course of signs of  injury?  How long did it take patients 
to recover and for laboratory tests to return to normal?  How many patients died?  Were there 
any long -term sequelae in survivors?  
 
 
2. Results, p. 11, line 15, "Further study…" How did the outcome vary between the pat ients in 
the different categories of SOS injury?  
 
 
3. Results, p. 13, Histology.  In stem -cell transplant related SOS, there is usually a component of 
veno -occlusive change, with partial to complete occlusion of small hepatic veins by loose 
collagen and cell s.  Were veno -occlusive changes seen in any of the biopsies?  If not, then that 
would be a significant diagnostic difference between the SOS seen in these two clinical 
situations.  
 
 
4. Discussion, p. 15, line 6.  "…soaked in liquid…"  This is unclear.  Does this mean that the 
patients are preparing tea from these plants?  How do patients get these plants?  Are they 
harvested by the patients themselves or are they included as components of traditional 
medicines? Or both?  
 
 
5. Discussion, p. 19, line 14.  The aut hors note that part of the public education campaign in 
China is to increase awareness of using the PA -containing plants only under the guidance of a 
physician or pharmacist.  Is there any legitimate medicinal use of these plants and if so, for what 
condit ions are they prescribed?  
 
 
6. Figure 3B, 2nd panel.  Rather than depicting a relatively normal portal area from this case, it 
would be better to have a high magnification (400x) photo of the sinusoids near the central vein, 
similar to the 2nd panel of Figur e 3A.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the auth ors. 
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an a dditional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
 
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in  the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my  report to the authors and, if the manuscript is accepted f or publication, my nam ed report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access C reative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Clinical characteri stics, CT Signs, and Patholo gical Findings of Pyrrolizidine 
Alkaloidsinduced Sinusoidal Obstructive Syndrome: a retrospective study  
 
Version: 0 Date: 15 Oct 2019  
 
Reviewer: David Kleiner  
 
Reviewer's report:  
 
This paper describes a cohort of patients who developed sinusoidal obstruction syndrome (SOS) 
from exposure to pyrrolizidine alkaloids.  Findings are compared to patients with Budd -Chiari 
syndrome and a mouse model of SOS.  Much of the discussion seems to be a summary of the 
results.  Pyrrolizidine alkaloid associated injury has been described before and it would be worth 
comparing this cohort to previous described case series to highlight similarities and differences 
in clinical presentation, imaging finding and histology.  
 
 
Specific com ments  
 
1. Results, p. 10, Clinical presentation.  The authors describe the clinical and associated 
laboratory findings at the time of presentation, but it would also be important to provide details 
of disease evolution.  What was the time course of signs of  injury?  How long did it take patients 
to recover and for laboratory tests to return to normal?  How many patients died?  Were there 
any long -term sequelae in survivors?  
 
 
2. Results, p. 11, line 15, "Further study…" How did the outcome vary between the pat ients in 
the different categories of SOS injury?  
 
 
3. Results, p. 13, Histology.  In stem -cell transplant related SOS, there is usually a component of 
veno -occlusive change, with partial to complete occlusion of small hepatic veins by loose 
collagen and cell s.  Were veno -occlusive changes seen in any of the biopsies?  If not, then that 
would be a significant diagnostic difference between the SOS seen in these two clinical 
situations.  
 
 
4. Discussion, p. 15, line 6.  "…soaked in liquid…"  This is unclear.  Does this mean that the 
patients are preparing tea from these plants?  How do patients get these plants?  Are they 
harvested by the patients themselves or are they included as components of traditional 
medicines? Or both?  
 
 
5. Discussion, p. 19, line 14.  The aut hors note that part of the public education campaign in 
China is to increase awareness of using the PA -containing plants only under the guidance of a 
physician or pharmacist.  Is there any legitimate medicinal use of these plants and if so, for what 
condit ions are they prescribed?  
 
 
6. Figure 3B, 2nd panel.  Rather than depicting a relatively normal portal area from this case, it 
would be better to have a high magnification (400x) photo of the sinusoids near the central vein, 
similar to the 2nd panel of Figur e 3A.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the auth ors. 
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an a dditional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
 
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in  the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my  report to the authors and, if the manuscript is accepted f or publication, my nam ed report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access C reative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant