Reviewer's report 
 Hepatopulmonary syndrome in patients with chronic liver disease: role of pulse oximetry Title: 
 1  26 February 2006 Version: Date: 
 Michael J Krowka Reviewer: 
Reviewer's report: 
General 
An interesting paper(with improvements needed) that tries to help focus on noninvasive diagnostic 
studies to screen for the existence of hepatopulmonary syndrome using positional, finger pulse 
oximetry. A large screening cohort with results that do stimulate additional questions in the small subgoup studied in greater detail. The writing style is a bit unusual (much more compact than 
normal), but that may be most efficient! I am more concerned about the specific data content and 
message to readers. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 1) The cohort includes those who have abnormal SaO2 AND positional drop in SaO2. How many had only abnormal SaO2, but no chnage with upright position? (see comments # 3 and # 5 below) 
2) The lung perfusion scanning methodology is unclear. Be more specific regarding how the shunt 
volume was calculated. This is important for other readers if they wish to duplicate your findings. Was the uptake measured over the brain only?; over the kidneys? What was your normal cutoff? 3) I believe it is important to show individual data on each of the 17 patients who fulfilled your criteria 
for further study; indeed only 4/17 (23.5%)had abnormal CEE (and HPS)along with the position 
change in SaO2 change. It is of significant interest that the other 13 had such change. Why? Is that common in hepatic hydrothorax or massive ascites?. I think it is not common in COPD unless the latter is severe (references?). One wonders how many had a drop of greater than 4%, but still had 
SaO2> 92%? 
4) If 9 patients with COPD had such change, a specific look at their individual PFTS would be of interest. How could they have COPD and still have similar PFTS to those with HPS? 5) The message herein. Most patients (76.5%) with aqbnormal SaO2 and SaO2 drops greater than 
or equal to 4% did NOT have HPS by CEE standards, so how can you say this is "a simple test to 
identify HPS". I do not disagree with the findings, but you will identify many others with non-HPS reasons for SaO2 change. Getting back to my other point in # 3, how many had SaO2 > 92 with or 
without position change that could also have HPS that you missed? In short, your test is quite 
nonspecific at this point and could have well missed others (albeit they were probably mild or 
subclincial)! Such an approach would still be helpful in deciding who should proceed to CEE and/or lung scanning. Obviously one would ask that your future work include addressing the question of 
whether HPS can exist without position change in SaO2 (and the answer is probably - but 
uncommon in early stages - in my opinion) 
6) Finally, show the actual PaO2 data in the HPS patients. The accepted diagnostic criteria is not SaO2, but rather Aa oxygen gradients and/or PaO2 (see the Eur Respir J 2004; 24: 861-880 paper from the ERS-EASL Task Force on pulmonary-hepatic vascular disorders for current and 
commonluy used historical references) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
7) I assume the CEE was by the tranthoracic rather than transesophageal method? 
8) On page 5 the sentence prior to " Such a patient fulfils the criteria for HPS" is confusing and the 
subsequent sentence (noted above) does not follow. Discretionary Revisions (which the author can choose to ignore) none 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. MJK 
Reviewer's report 
 Hepatopulmonary syndrome in patients with chronic liver disease: role of pulse oximetry Title: 
 1  26 February 2006 Version: Date: 
 Michael J Krowka Reviewer: 
Reviewer's report: 
General 
An interesting paper(with improvements needed) that tries to help focus on noninvasive diagnostic 
studies to screen for the existence of hepatopulmonary syndrome using positional, finger pulse 
oximetry. A large screening cohort with results that do stimulate additional questions in the small subgoup studied in greater detail. The writing style is a bit unusual (much more compact than 
normal), but that may be most efficient! I am more concerned about the specific data content and 
message to readers. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 1) The cohort includes those who have abnormal SaO2 AND positional drop in SaO2. How many had only abnormal SaO2, but no chnage with upright position? (see comments # 3 and # 5 below) 
2) The lung perfusion scanning methodology is unclear. Be more specific regarding how the shunt 
volume was calculated. This is important for other readers if they wish to duplicate your findings. Was the uptake measured over the brain only?; over the kidneys? What was your normal cutoff? 3) I believe it is important to show individual data on each of the 17 patients who fulfilled your criteria 
for further study; indeed only 4/17 (23.5%)had abnormal CEE (and HPS)along with the position 
change in SaO2 change. It is of significant interest that the other 13 had such change. Why? Is that common in hepatic hydrothorax or massive ascites?. I think it is not common in COPD unless the latter is severe (references?). One wonders how many had a drop of greater than 4%, but still had 
SaO2> 92%? 
4) If 9 patients with COPD had such change, a specific look at their individual PFTS would be of interest. How could they have COPD and still have similar PFTS to those with HPS? 5) The message herein. Most patients (76.5%) with aqbnormal SaO2 and SaO2 drops greater than 
or equal to 4% did NOT have HPS by CEE standards, so how can you say this is "a simple test to 
identify HPS". I do not disagree with the findings, but you will identify many others with non-HPS reasons for SaO2 change. Getting back to my other point in # 3, how many had SaO2 > 92 with or 
without position change that could also have HPS that you missed? In short, your test is quite 
nonspecific at this point and could have well missed others (albeit they were probably mild or 
subclincial)! Such an approach would still be helpful in deciding who should proceed to CEE and/or lung scanning. Obviously one would ask that your future work include addressing the question of 
whether HPS can exist without position change in SaO2 (and the answer is probably - but 
uncommon in early stages - in my opinion) 
6) Finally, show the actual PaO2 data in the HPS patients. The accepted diagnostic criteria is not SaO2, but rather Aa oxygen gradients and/or PaO2 (see the Eur Respir J 2004; 24: 861-880 paper from the ERS-EASL Task Force on pulmonary-hepatic vascular disorders for current and 
commonluy used historical references) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
7) I assume the CEE was by the tranthoracic rather than transesophageal method? 
8) On page 5 the sentence prior to " Such a patient fulfils the criteria for HPS" is confusing and the 
subsequent sentence (noted above) does not follow. Discretionary Revisions (which the author can choose to ignore) none 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. MJK 
Please review this paper.
user
Reviewer's report 
 Hepatopulmonary syndrome in patients with chronic liver disease: role of pulse oximetry Title: 
 1  26 February 2006 Version: Date: 
 Michael J Krowka Reviewer: 
Reviewer's report: 
General 
An interesting paper(with improvements needed) that tries to help focus on noninvasive diagnostic 
studies to screen for the existence of hepatopulmonary syndrome using positional, finger pulse 
oximetry. A large screening cohort with results that do stimulate additional questions in the small subgoup studied in greater detail. The writing style is a bit unusual (much more compact than 
normal), but that may be most efficient! I am more concerned about the specific data content and 
message to readers. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 1) The cohort includes those who have abnormal SaO2 AND positional drop in SaO2. How many had only abnormal SaO2, but no chnage with upright position? (see comments # 3 and # 5 below) 
2) The lung perfusion scanning methodology is unclear. Be more specific regarding how the shunt 
volume was calculated. This is important for other readers if they wish to duplicate your findings. Was the uptake measured over the brain only?; over the kidneys? What was your normal cutoff? 3) I believe it is important to show individual data on each of the 17 patients who fulfilled your criteria 
for further study; indeed only 4/17 (23.5%)had abnormal CEE (and HPS)along with the position 
change in SaO2 change. It is of significant interest that the other 13 had such change. Why? Is that common in hepatic hydrothorax or massive ascites?. I think it is not common in COPD unless the latter is severe (references?). One wonders how many had a drop of greater than 4%, but still had 
SaO2> 92%? 
4) If 9 patients with COPD had such change, a specific look at their individual PFTS would be of interest. How could they have COPD and still have similar PFTS to those with HPS? 5) The message herein. Most patients (76.5%) with aqbnormal SaO2 and SaO2 drops greater than 
or equal to 4% did NOT have HPS by CEE standards, so how can you say this is "a simple test to 
identify HPS". I do not disagree with the findings, but you will identify many others with non-HPS reasons for SaO2 change. Getting back to my other point in # 3, how many had SaO2 > 92 with or 
without position change that could also have HPS that you missed? In short, your test is quite 
nonspecific at this point and could have well missed others (albeit they were probably mild or 
subclincial)! Such an approach would still be helpful in deciding who should proceed to CEE and/or lung scanning. Obviously one would ask that your future work include addressing the question of 
whether HPS can exist without position change in SaO2 (and the answer is probably - but 
uncommon in early stages - in my opinion) 
6) Finally, show the actual PaO2 data in the HPS patients. The accepted diagnostic criteria is not SaO2, but rather Aa oxygen gradients and/or PaO2 (see the Eur Respir J 2004; 24: 861-880 paper from the ERS-EASL Task Force on pulmonary-hepatic vascular disorders for current and 
commonluy used historical references) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
7) I assume the CEE was by the tranthoracic rather than transesophageal method? 
8) On page 5 the sentence prior to " Such a patient fulfils the criteria for HPS" is confusing and the 
subsequent sentence (noted above) does not follow. Discretionary Revisions (which the author can choose to ignore) none 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. MJK 
assistant