Reviewer's report 
 The relation between plasma tyrosine concentration and fatigue in primary biliary cirrhosis and Title: 
primary sclerosing cholangitis 
 2  12 December 2004 Version: Date: 
 Daniel Forton Reviewer: 
Reviewer's report: 
General 
Although the authors have attempted a very full rebuttal, I remain unconvinced about the central 
conclusion that fatigue in PBC is related to somehow discrepantly normal tyrosine levels. The 
cause(s) of fatigue in PBC and PSC are likely to be the same, yet no relationship between tyrosine 
and fatigue was observed in the PSC group. This has not been discussed. 
Furthermore, the authors base the rationale for this study on previous reports of a correlation 
between elevated tryptophan and fatigue in non-hepatic conditions. The opposite results in this study 
in the PBC group again have not been discussed. 
I am still of the opinion that the data in this study are not internally consistent and that it is difficult to 
draw any conclusions regarding fatigue and amino acid levels in these patients groups. I acknowledge that the authors have qualified their conclusions with a number of caveats. 
Since the tyrosine levels in the PBC group were not low (the fatigued PBC patients still had a higher 
mean tyrosine level than the controls) all references to low tyrosine levels should be corrected to normal tyrosine levels. 
The legend for table 3 appears incorrect 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
------------------------------------------------------------------------------- 
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 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: 
Reviewer's report 
 The relation between plasma tyrosine concentration and fatigue in primary biliary cirrhosis and Title: 
primary sclerosing cholangitis 
 2  12 December 2004 Version: Date: 
 Daniel Forton Reviewer: 
Reviewer's report: 
General 
Although the authors have attempted a very full rebuttal, I remain unconvinced about the central 
conclusion that fatigue in PBC is related to somehow discrepantly normal tyrosine levels. The 
cause(s) of fatigue in PBC and PSC are likely to be the same, yet no relationship between tyrosine 
and fatigue was observed in the PSC group. This has not been discussed. 
Furthermore, the authors base the rationale for this study on previous reports of a correlation 
between elevated tryptophan and fatigue in non-hepatic conditions. The opposite results in this study 
in the PBC group again have not been discussed. 
I am still of the opinion that the data in this study are not internally consistent and that it is difficult to 
draw any conclusions regarding fatigue and amino acid levels in these patients groups. I acknowledge that the authors have qualified their conclusions with a number of caveats. 
Since the tyrosine levels in the PBC group were not low (the fatigued PBC patients still had a higher 
mean tyrosine level than the controls) all references to low tyrosine levels should be corrected to normal tyrosine levels. 
The legend for table 3 appears incorrect 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
------------------------------------------------------------------------------- 
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 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: 
Please review this paper.
user
Reviewer's report 
 The relation between plasma tyrosine concentration and fatigue in primary biliary cirrhosis and Title: 
primary sclerosing cholangitis 
 2  12 December 2004 Version: Date: 
 Daniel Forton Reviewer: 
Reviewer's report: 
General 
Although the authors have attempted a very full rebuttal, I remain unconvinced about the central 
conclusion that fatigue in PBC is related to somehow discrepantly normal tyrosine levels. The 
cause(s) of fatigue in PBC and PSC are likely to be the same, yet no relationship between tyrosine 
and fatigue was observed in the PSC group. This has not been discussed. 
Furthermore, the authors base the rationale for this study on previous reports of a correlation 
between elevated tryptophan and fatigue in non-hepatic conditions. The opposite results in this study 
in the PBC group again have not been discussed. 
I am still of the opinion that the data in this study are not internally consistent and that it is difficult to 
draw any conclusions regarding fatigue and amino acid levels in these patients groups. I acknowledge that the authors have qualified their conclusions with a number of caveats. 
Since the tyrosine levels in the PBC group were not low (the fatigued PBC patients still had a higher 
mean tyrosine level than the controls) all references to low tyrosine levels should be corrected to normal tyrosine levels. 
The legend for table 3 appears incorrect 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
------------------------------------------------------------------------------- 
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 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: 
assistant