Reviewer's report
 Primary biliary cirrhosis and autoimmune cholangitis are not associated with coeliac disease Title:
Authors:
Costantinos Chatzicostas (matrix01gr@yahoo.gr )
Maria Roussomoustakaki (rousso@edu.uch.gr )
Dimitrios Drygiannakis (jadrigmh@danae.med.uch.gr )
Maria Niniraki (photeini@in.gr )
Maria Tzardi (photeini@in.gr )
Mary Koulentaki (kofterid@med.uoc.gr )
Philippos Dimoulios (fdimoul@hotmail.com )
Ioannis Mouzas (mouzas@med.uoc.gr )
Elias Kouroumalis (kouroum@med.uoc.gr )
 1  7 Feb 2002 Version: Date:
 Dr Jerry Kingham Reviewer:
 A paper whose findings are important to those with closely related research interests Level of interest:
 Accept after discretionary revisions Advice on publication:
This study from Crete looks at serological markers of coeliac disease in 62 patients with PBC and 17 
with AIC and compares results with a control population of healthy blood donors. Antibodies to gliadin 
were present in one fifth of PBC and one third of AIC sera respectively, antibodies to tissue 
transglutaminase were less common while endomysial antibodies were not detected in any sera. Two 
thirds of those patients with detectable antibodies underwent duodenal biopsy but all were histologically 
normal. The authors conclude that no increased risk of coeliac disease could be shown in PBC or AIC 
but that such patients may have false positive serological responses to gliadin and TTG. 
Comment 
The method of case ascertainment is not defined so this does not constitute an epidemiological study. Presumably sera were collected opportunistically from patients attending liver clinic. Thus there is no 
denominator for this group of patients with PBC or AIC. The prevalence of coeliac disease in Crete is 
not given and is perhaps not known (but is probably low). In an area of low CD prevalence the failure to detect a case amongst 62 patients with PBC does not preclude an association. In the introduction and the discussion 4 studies (references 10 to 13) are cited as not confirming an association between PBC 
and coeliac disease. Reference 10, a letter from Fidler et al, is repeatedly misquoted as this actually 
confirmed an association between CD and PBC (2 of 87 patients) albeit less pronounced than in the index study to which it referred (reference 8). The other studies referred to (references 11 to 13) were similar in design to the current study from Crete, whereas those studies showing a positive association 
were epidemiologically based on large populations (references 8 and 9) or were much larger, more 
empowered studies (ref 32). 
The observations on the lack of specificity of anti-gliadin antibodies and antibodies to guinea pig TTG in 
patients with chronic liver disease are valid and corroborate recent reports from several sources. 
The epidemiological evidence linking CD and PBC is strong, and the negative results of an 
observational study such as this one from Crete does not disprove the association. Perhaps the more 
practical consideration is as to whether screening for one condition in the presence of the other is a 
worthwhile exercise in a particular population. This decision has to be based in part on the prevalence 
of the conditions individually, thus screening has been advocated in Celtic populations such as Wales 
and Ireland where both these diseases are particularly prevalent but may not be appropriate in 
Scandinavia. Clinicians have to decide on the benefits of screening based both on knowledge of their 
local population and published reports from other populations. 
Competing interests:
None declared.
Reviewer's report
 Primary biliary cirrhosis and autoimmune cholangitis are not associated with coeliac disease Title:
Authors:
Costantinos Chatzicostas (matrix01gr@yahoo.gr )
Maria Roussomoustakaki (rousso@edu.uch.gr )
Dimitrios Drygiannakis (jadrigmh@danae.med.uch.gr )
Maria Niniraki (photeini@in.gr )
Maria Tzardi (photeini@in.gr )
Mary Koulentaki (kofterid@med.uoc.gr )
Philippos Dimoulios (fdimoul@hotmail.com )
Ioannis Mouzas (mouzas@med.uoc.gr )
Elias Kouroumalis (kouroum@med.uoc.gr )
 1  7 Feb 2002 Version: Date:
 Dr Jerry Kingham Reviewer:
 A paper whose findings are important to those with closely related research interests Level of interest:
 Accept after discretionary revisions Advice on publication:
This study from Crete looks at serological markers of coeliac disease in 62 patients with PBC and 17 
with AIC and compares results with a control population of healthy blood donors. Antibodies to gliadin 
were present in one fifth of PBC and one third of AIC sera respectively, antibodies to tissue 
transglutaminase were less common while endomysial antibodies were not detected in any sera. Two 
thirds of those patients with detectable antibodies underwent duodenal biopsy but all were histologically 
normal. The authors conclude that no increased risk of coeliac disease could be shown in PBC or AIC 
but that such patients may have false positive serological responses to gliadin and TTG. 
Comment 
The method of case ascertainment is not defined so this does not constitute an epidemiological study. Presumably sera were collected opportunistically from patients attending liver clinic. Thus there is no 
denominator for this group of patients with PBC or AIC. The prevalence of coeliac disease in Crete is 
not given and is perhaps not known (but is probably low). In an area of low CD prevalence the failure to detect a case amongst 62 patients with PBC does not preclude an association. In the introduction and the discussion 4 studies (references 10 to 13) are cited as not confirming an association between PBC 
and coeliac disease. Reference 10, a letter from Fidler et al, is repeatedly misquoted as this actually 
confirmed an association between CD and PBC (2 of 87 patients) albeit less pronounced than in the index study to which it referred (reference 8). The other studies referred to (references 11 to 13) were similar in design to the current study from Crete, whereas those studies showing a positive association 
were epidemiologically based on large populations (references 8 and 9) or were much larger, more 
empowered studies (ref 32). 
The observations on the lack of specificity of anti-gliadin antibodies and antibodies to guinea pig TTG in 
patients with chronic liver disease are valid and corroborate recent reports from several sources. 
The epidemiological evidence linking CD and PBC is strong, and the negative results of an 
observational study such as this one from Crete does not disprove the association. Perhaps the more 
practical consideration is as to whether screening for one condition in the presence of the other is a 
worthwhile exercise in a particular population. This decision has to be based in part on the prevalence 
of the conditions individually, thus screening has been advocated in Celtic populations such as Wales 
and Ireland where both these diseases are particularly prevalent but may not be appropriate in 
Scandinavia. Clinicians have to decide on the benefits of screening based both on knowledge of their 
local population and published reports from other populations. 
Competing interests:
None declared.
Please review this paper.
user
Reviewer's report
 Primary biliary cirrhosis and autoimmune cholangitis are not associated with coeliac disease Title:
Authors:
Costantinos Chatzicostas (matrix01gr@yahoo.gr )
Maria Roussomoustakaki (rousso@edu.uch.gr )
Dimitrios Drygiannakis (jadrigmh@danae.med.uch.gr )
Maria Niniraki (photeini@in.gr )
Maria Tzardi (photeini@in.gr )
Mary Koulentaki (kofterid@med.uoc.gr )
Philippos Dimoulios (fdimoul@hotmail.com )
Ioannis Mouzas (mouzas@med.uoc.gr )
Elias Kouroumalis (kouroum@med.uoc.gr )
 1  7 Feb 2002 Version: Date:
 Dr Jerry Kingham Reviewer:
 A paper whose findings are important to those with closely related research interests Level of interest:
 Accept after discretionary revisions Advice on publication:
This study from Crete looks at serological markers of coeliac disease in 62 patients with PBC and 17 
with AIC and compares results with a control population of healthy blood donors. Antibodies to gliadin 
were present in one fifth of PBC and one third of AIC sera respectively, antibodies to tissue 
transglutaminase were less common while endomysial antibodies were not detected in any sera. Two 
thirds of those patients with detectable antibodies underwent duodenal biopsy but all were histologically 
normal. The authors conclude that no increased risk of coeliac disease could be shown in PBC or AIC 
but that such patients may have false positive serological responses to gliadin and TTG. 
Comment 
The method of case ascertainment is not defined so this does not constitute an epidemiological study. Presumably sera were collected opportunistically from patients attending liver clinic. Thus there is no 
denominator for this group of patients with PBC or AIC. The prevalence of coeliac disease in Crete is 
not given and is perhaps not known (but is probably low). In an area of low CD prevalence the failure to detect a case amongst 62 patients with PBC does not preclude an association. In the introduction and the discussion 4 studies (references 10 to 13) are cited as not confirming an association between PBC 
and coeliac disease. Reference 10, a letter from Fidler et al, is repeatedly misquoted as this actually 
confirmed an association between CD and PBC (2 of 87 patients) albeit less pronounced than in the index study to which it referred (reference 8). The other studies referred to (references 11 to 13) were similar in design to the current study from Crete, whereas those studies showing a positive association 
were epidemiologically based on large populations (references 8 and 9) or were much larger, more 
empowered studies (ref 32). 
The observations on the lack of specificity of anti-gliadin antibodies and antibodies to guinea pig TTG in 
patients with chronic liver disease are valid and corroborate recent reports from several sources. 
The epidemiological evidence linking CD and PBC is strong, and the negative results of an 
observational study such as this one from Crete does not disprove the association. Perhaps the more 
practical consideration is as to whether screening for one condition in the presence of the other is a 
worthwhile exercise in a particular population. This decision has to be based in part on the prevalence 
of the conditions individually, thus screening has been advocated in Celtic populations such as Wales 
and Ireland where both these diseases are particularly prevalent but may not be appropriate in 
Scandinavia. Clinicians have to decide on the benefits of screening based both on knowledge of their 
local population and published reports from other populations. 
Competing interests:
None declared.
assistant