Title: IgG4-related cholangitis – distinguishing from other benign biliary strictures: clinical
features, imaging, and response to treatment: a retrospective study
Version: 1 Date: 20 May 2025
Reviewer:  Nabeel Azeem
Reviewer's report:
It would be helpful if the authors could clarify/be more specific on how they identified the patient
population prior to chart review. Did they do a keyword search of an electronic medical record to
identify all biliary strictures, or were billing codes used, or was there a prospectively maintained
list of patients with biliary strictures.
Was EUS utilized for sampling of any adjacent lymphadenopathy?
I would disagree with the definition given for ‘Indeterminate biliary stricture’. These are
strictures where the initial work up failed to determine an aetiology but statistically most of them
are malignant. Therefore, many of these would not remain stable over time. The ones that did
remain stable by definition were benign. This is more clear in the flow chart but the definition
should be changed.
What modality was used to determine the thickness of the bile duct? EUS/MRCP/CT? There
will likely be between modality difference even in the same patient.
“However, patients with IRC tended to be older, with a mean age of 65 years, compared to 58.5
years in those with other BBS (p=0.085)” This comparison did not reach statistical significance
and therefore there is no difference in age between the two groups.
Using the data you already have, it would be useful to report sensitivity and specificity of
elevated IgG4 in IRC compared to the rest of the BBS cohort. ROC curve could then be generated
to understand what IgG4 cut off would be useful.
How were the length of the strictures determined? On MRCP or ERCP? As reported at the time
of procedure/imaging or measured post-hoc?
Why was there any response to steroids in the BBS group (10.5%)? If they responded to steroids,
wouldn’t they be in the IRC group/have IgG4-cholangiopathy?
“Among the other BBS groups, the aetiologies included stone-induced bile duct stricture (37%),
indeterminate biliary strictures (18%), chronic pancreatitis (18%), and other BBS (25%).” ---
Indeterminate biliary stricture is not an aetiology. By definition, it means we do not know what
the etiology is.
“Additionally, the incidence of ascending cholangitis was significantly lower in the IRC group
compared with the other BBS groups (15.8% vs. 66.7%; p < 0.001) in our study.”--- Shouldn’t
this be 15.8% vs 45.3% according to table 1?
Title: IgG4-related cholangitis – distinguishing from other benign biliary strictures: clinical
features, imaging, and response to treatment: a retrospective study
Version: 1 Date: 20 May 2025
Reviewer:  Nabeel Azeem
Reviewer's report:
It would be helpful if the authors could clarify/be more specific on how they identified the patient
population prior to chart review. Did they do a keyword search of an electronic medical record to
identify all biliary strictures, or were billing codes used, or was there a prospectively maintained
list of patients with biliary strictures.
Was EUS utilized for sampling of any adjacent lymphadenopathy?
I would disagree with the definition given for ‘Indeterminate biliary stricture’. These are
strictures where the initial work up failed to determine an aetiology but statistically most of them
are malignant. Therefore, many of these would not remain stable over time. The ones that did
remain stable by definition were benign. This is more clear in the flow chart but the definition
should be changed.
What modality was used to determine the thickness of the bile duct? EUS/MRCP/CT? There
will likely be between modality difference even in the same patient.
“However, patients with IRC tended to be older, with a mean age of 65 years, compared to 58.5
years in those with other BBS (p=0.085)” This comparison did not reach statistical significance
and therefore there is no difference in age between the two groups.
Using the data you already have, it would be useful to report sensitivity and specificity of
elevated IgG4 in IRC compared to the rest of the BBS cohort. ROC curve could then be generated
to understand what IgG4 cut off would be useful.
How were the length of the strictures determined? On MRCP or ERCP? As reported at the time
of procedure/imaging or measured post-hoc?
Why was there any response to steroids in the BBS group (10.5%)? If they responded to steroids,
wouldn’t they be in the IRC group/have IgG4-cholangiopathy?
“Among the other BBS groups, the aetiologies included stone-induced bile duct stricture (37%),
indeterminate biliary strictures (18%), chronic pancreatitis (18%), and other BBS (25%).” ---
Indeterminate biliary stricture is not an aetiology. By definition, it means we do not know what
the etiology is.
“Additionally, the incidence of ascending cholangitis was significantly lower in the IRC group
compared with the other BBS groups (15.8% vs. 66.7%; p < 0.001) in our study.”--- Shouldn’t
this be 15.8% vs 45.3% according to table 1?
Please review this paper.
user
Title: IgG4-related cholangitis – distinguishing from other benign biliary strictures: clinical
features, imaging, and response to treatment: a retrospective study
Version: 1 Date: 20 May 2025
Reviewer:  Nabeel Azeem
Reviewer's report:
It would be helpful if the authors could clarify/be more specific on how they identified the patient
population prior to chart review. Did they do a keyword search of an electronic medical record to
identify all biliary strictures, or were billing codes used, or was there a prospectively maintained
list of patients with biliary strictures.
Was EUS utilized for sampling of any adjacent lymphadenopathy?
I would disagree with the definition given for ‘Indeterminate biliary stricture’. These are
strictures where the initial work up failed to determine an aetiology but statistically most of them
are malignant. Therefore, many of these would not remain stable over time. The ones that did
remain stable by definition were benign. This is more clear in the flow chart but the definition
should be changed.
What modality was used to determine the thickness of the bile duct? EUS/MRCP/CT? There
will likely be between modality difference even in the same patient.
“However, patients with IRC tended to be older, with a mean age of 65 years, compared to 58.5
years in those with other BBS (p=0.085)” This comparison did not reach statistical significance
and therefore there is no difference in age between the two groups.
Using the data you already have, it would be useful to report sensitivity and specificity of
elevated IgG4 in IRC compared to the rest of the BBS cohort. ROC curve could then be generated
to understand what IgG4 cut off would be useful.
How were the length of the strictures determined? On MRCP or ERCP? As reported at the time
of procedure/imaging or measured post-hoc?
Why was there any response to steroids in the BBS group (10.5%)? If they responded to steroids,
wouldn’t they be in the IRC group/have IgG4-cholangiopathy?
“Among the other BBS groups, the aetiologies included stone-induced bile duct stricture (37%),
indeterminate biliary strictures (18%), chronic pancreatitis (18%), and other BBS (25%).” ---
Indeterminate biliary stricture is not an aetiology. By definition, it means we do not know what
the etiology is.
“Additionally, the incidence of ascending cholangitis was significantly lower in the IRC group
compared with the other BBS groups (15.8% vs. 66.7%; p < 0.001) in our study.”--- Shouldn’t
this be 15.8% vs 45.3% according to table 1?
assistant