Title: Evaluation of autoimmune liver disease natural history in patients referred to Middle East
Liver Diseases (MELD) center
Version: 0 Date: 07 Aug 2023
Reviewer's report:
In this retrospective study, Seyed Erfan Mehdi Nejad and colleagues, aimed to investigate
the natural history and characteristics of Autoimmune liver diseases (AILD) in an Iranian
population.
The main clinical/laboratory features of natural history, including auto-Antibodies, response to
treatment, and cirrhotic status along with demographic data of patients with AILD [Autoimmune
Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and
Overlap Syndrome]  were studied.
Overall, two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC,
48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were
included.
They found that autoantibodies were important diagnostic markers for the AIH and PBC but
not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with
AIH and overlap syndrome respectively and 21 patients (11 (6.9%) of AIH and 10 (20.8%) of
overlap syndrome) were non-responders. Other patients in these two categories were considered
as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC
and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis
regression was observed in some AIH and PBC patients.
They concluded that appropriate medication management for AILD patients may leads
to regression from cirrhosis and improvement of manifestations; while discontinuation of
medication may cause relapses. However, patient suffering from PSC showed limited response
to treatment.
The study has interest since geographical differences in clinical/laboratory features of
autoimmune liver diseases occur and data from the Iranian area are lacking. However, to further
improve the clinical impact of this study some important information should be provided.
-Study population: the authors stated that they used the simplified AIH diagnosis criteria
(2008). However, to compare their result with previously published studies, they should
also report whether the AIH diagnosis could be also confirmed with the more accurate/
sensitive diagnostic criteria of the original revised (1999) score, because the original and
the simplified diagnostic scores have differences as described in a comprehensive review
(Diagnosis and therapy of autoimmune hepatitis. Mini Rev Med Chem. 2009 Jun;9(7):847-60.
doi: 10.2174/138955709788452676.). Moreover, for AIH patients with "acute presentation",
it has been recently demonstrated that the simplified scoring system does not perform as
the original diagnostic score because AIH patients with acute presentation not rarely are
autoantibody negative and have normal serum gamma-globulin levels as recently demonstrated
(Limitation of the simplified scoring system for the diagnosis of autoimmune Hepatitis with
acute onset. Liver Int. 2021 Mar;41(3):529-534. doi: 10.1111/liv.14778.).
-if they routinely used the simplified criteria, this should be supported by recalling the
validation of the simplified score in clinical practice as previously reported (Validation of
simplified diagnostic criteria for autoimmune hepatitis in Italian patients. Hepatology. 2009
May;49(5):1782-3; ).
-Age of diagnosis: it appears that there are no AIH patients diagnosed after 50 years.
In this regard, the author should underline that AIH diagnosis is reported also in the
elderly, as previously demonstrated (Clinical features of type 1 autoimmune hepatitis in
elderly Italian patients. Aliment Pharmacol Ther. 2005 May 15;21(10):1273-7. doi: 10.1111/
j.1365-2036.2005.02488.x. ).
-Regarding the clinical significance of Fatigue in PBC patients, the authors should describe
whether their PBC patients suffering from fatigue at diagnosis had a worse prognosis because
a previous study demonstrated that fatigue and pruritus at diagnosis identify PBC patients with
the worst prognosis (Fatigue and pruritus at onset identify a more aggressive subset of primary
biliary cirrhosis. Liver Int. 2015 Feb;35(2):636-41. ).
-A last point worth mentioning, is the impact of different genetic backgrounds to explain the
different autoantibody/clinical profiles of AIH worldwide as previously demonstrated (Genetic
distinctions between autoimmune hepatitis in Italy and North America. World J Gastroenterol.
2005 Mar 28;11(12):1862-6.).
-Please, add details on laboratory techniques used for autoantibody detection.
Title: Evaluation of autoimmune liver disease natural history in patients referred to Middle East
Liver Diseases (MELD) center
Version: 0 Date: 07 Aug 2023
Reviewer's report:
In this retrospective study, Seyed Erfan Mehdi Nejad and colleagues, aimed to investigate
the natural history and characteristics of Autoimmune liver diseases (AILD) in an Iranian
population.
The main clinical/laboratory features of natural history, including auto-Antibodies, response to
treatment, and cirrhotic status along with demographic data of patients with AILD [Autoimmune
Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and
Overlap Syndrome]  were studied.
Overall, two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC,
48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were
included.
They found that autoantibodies were important diagnostic markers for the AIH and PBC but
not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with
AIH and overlap syndrome respectively and 21 patients (11 (6.9%) of AIH and 10 (20.8%) of
overlap syndrome) were non-responders. Other patients in these two categories were considered
as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC
and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis
regression was observed in some AIH and PBC patients.
They concluded that appropriate medication management for AILD patients may leads
to regression from cirrhosis and improvement of manifestations; while discontinuation of
medication may cause relapses. However, patient suffering from PSC showed limited response
to treatment.
The study has interest since geographical differences in clinical/laboratory features of
autoimmune liver diseases occur and data from the Iranian area are lacking. However, to further
improve the clinical impact of this study some important information should be provided.
-Study population: the authors stated that they used the simplified AIH diagnosis criteria
(2008). However, to compare their result with previously published studies, they should
also report whether the AIH diagnosis could be also confirmed with the more accurate/
sensitive diagnostic criteria of the original revised (1999) score, because the original and
the simplified diagnostic scores have differences as described in a comprehensive review
(Diagnosis and therapy of autoimmune hepatitis. Mini Rev Med Chem. 2009 Jun;9(7):847-60.
doi: 10.2174/138955709788452676.). Moreover, for AIH patients with "acute presentation",
it has been recently demonstrated that the simplified scoring system does not perform as
the original diagnostic score because AIH patients with acute presentation not rarely are
autoantibody negative and have normal serum gamma-globulin levels as recently demonstrated
(Limitation of the simplified scoring system for the diagnosis of autoimmune Hepatitis with
acute onset. Liver Int. 2021 Mar;41(3):529-534. doi: 10.1111/liv.14778.).
-if they routinely used the simplified criteria, this should be supported by recalling the
validation of the simplified score in clinical practice as previously reported (Validation of
simplified diagnostic criteria for autoimmune hepatitis in Italian patients. Hepatology. 2009
May;49(5):1782-3; ).
-Age of diagnosis: it appears that there are no AIH patients diagnosed after 50 years.
In this regard, the author should underline that AIH diagnosis is reported also in the
elderly, as previously demonstrated (Clinical features of type 1 autoimmune hepatitis in
elderly Italian patients. Aliment Pharmacol Ther. 2005 May 15;21(10):1273-7. doi: 10.1111/
j.1365-2036.2005.02488.x. ).
-Regarding the clinical significance of Fatigue in PBC patients, the authors should describe
whether their PBC patients suffering from fatigue at diagnosis had a worse prognosis because
a previous study demonstrated that fatigue and pruritus at diagnosis identify PBC patients with
the worst prognosis (Fatigue and pruritus at onset identify a more aggressive subset of primary
biliary cirrhosis. Liver Int. 2015 Feb;35(2):636-41. ).
-A last point worth mentioning, is the impact of different genetic backgrounds to explain the
different autoantibody/clinical profiles of AIH worldwide as previously demonstrated (Genetic
distinctions between autoimmune hepatitis in Italy and North America. World J Gastroenterol.
2005 Mar 28;11(12):1862-6.).
-Please, add details on laboratory techniques used for autoantibody detection.
Please review this paper.
user
Title: Evaluation of autoimmune liver disease natural history in patients referred to Middle East
Liver Diseases (MELD) center
Version: 0 Date: 07 Aug 2023
Reviewer's report:
In this retrospective study, Seyed Erfan Mehdi Nejad and colleagues, aimed to investigate
the natural history and characteristics of Autoimmune liver diseases (AILD) in an Iranian
population.
The main clinical/laboratory features of natural history, including auto-Antibodies, response to
treatment, and cirrhotic status along with demographic data of patients with AILD [Autoimmune
Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and
Overlap Syndrome]  were studied.
Overall, two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC,
48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were
included.
They found that autoantibodies were important diagnostic markers for the AIH and PBC but
not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with
AIH and overlap syndrome respectively and 21 patients (11 (6.9%) of AIH and 10 (20.8%) of
overlap syndrome) were non-responders. Other patients in these two categories were considered
as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC
and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis
regression was observed in some AIH and PBC patients.
They concluded that appropriate medication management for AILD patients may leads
to regression from cirrhosis and improvement of manifestations; while discontinuation of
medication may cause relapses. However, patient suffering from PSC showed limited response
to treatment.
The study has interest since geographical differences in clinical/laboratory features of
autoimmune liver diseases occur and data from the Iranian area are lacking. However, to further
improve the clinical impact of this study some important information should be provided.
-Study population: the authors stated that they used the simplified AIH diagnosis criteria
(2008). However, to compare their result with previously published studies, they should
also report whether the AIH diagnosis could be also confirmed with the more accurate/
sensitive diagnostic criteria of the original revised (1999) score, because the original and
the simplified diagnostic scores have differences as described in a comprehensive review
(Diagnosis and therapy of autoimmune hepatitis. Mini Rev Med Chem. 2009 Jun;9(7):847-60.
doi: 10.2174/138955709788452676.). Moreover, for AIH patients with "acute presentation",
it has been recently demonstrated that the simplified scoring system does not perform as
the original diagnostic score because AIH patients with acute presentation not rarely are
autoantibody negative and have normal serum gamma-globulin levels as recently demonstrated
(Limitation of the simplified scoring system for the diagnosis of autoimmune Hepatitis with
acute onset. Liver Int. 2021 Mar;41(3):529-534. doi: 10.1111/liv.14778.).
-if they routinely used the simplified criteria, this should be supported by recalling the
validation of the simplified score in clinical practice as previously reported (Validation of
simplified diagnostic criteria for autoimmune hepatitis in Italian patients. Hepatology. 2009
May;49(5):1782-3; ).
-Age of diagnosis: it appears that there are no AIH patients diagnosed after 50 years.
In this regard, the author should underline that AIH diagnosis is reported also in the
elderly, as previously demonstrated (Clinical features of type 1 autoimmune hepatitis in
elderly Italian patients. Aliment Pharmacol Ther. 2005 May 15;21(10):1273-7. doi: 10.1111/
j.1365-2036.2005.02488.x. ).
-Regarding the clinical significance of Fatigue in PBC patients, the authors should describe
whether their PBC patients suffering from fatigue at diagnosis had a worse prognosis because
a previous study demonstrated that fatigue and pruritus at diagnosis identify PBC patients with
the worst prognosis (Fatigue and pruritus at onset identify a more aggressive subset of primary
biliary cirrhosis. Liver Int. 2015 Feb;35(2):636-41. ).
-A last point worth mentioning, is the impact of different genetic backgrounds to explain the
different autoantibody/clinical profiles of AIH worldwide as previously demonstrated (Genetic
distinctions between autoimmune hepatitis in Italy and North America. World J Gastroenterol.
2005 Mar 28;11(12):1862-6.).
-Please, add details on laboratory techniques used for autoantibody detection.
assistant