Title: Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis
Version: 1 Date: 16 Nov 2020
Reviewer's report:
In this small retrospective cohort study 12 patients with AS-AIH are described on clinical
characteristics, histology and short term prognosis. No control group was included. AS-AIH is
a rare presentation of AIH which can be a challenge to diagnose and treat.
I have some comments regarding this study
1) Patients with underlying cirrhosis were excluded from the present study but form part of the
population of AIH that present with coagulopathy. How many patients with underlying cirrhosis
were excluded from the study? For treating physicians this is a relevant population.
2) How many patients presented with encephalopathy (AS-AIH with acute liver failure
according to a recent review by Rahim et al. Liver Transplantation 2019)
3) In the article is commented on the prevalence of seronegative AIH in AS-AIH. In the
introduction and discussion it is mentioned as a feature that occurs more often in AS-AIH. In
the present study it was around 25% of patients. No control group of AIH patients were included
and in chronic presentation up to 34% of seronegative AIH was reported according to reference
17. I’m not sure if it is occurring more often in AS-AIH patients
4) All liver biopsies were revised and only 3 patients had interface hepatitis. Interface hepatitis
is a hallmark feature of AIH and present in all scoring systems. Do you have an explanation why
interface hepatitis was present in so few patients?
5) Two patients with pour outcome are described were the interval between symptoms and
treatment initiation was 60 and 70 days. At what timepoint are de baseline characteristics of
these patients in table 1 taken? Is there an explanation for the diagnostic delay in these patients?
6) The authors state that treatment with steroids is not proven effective in AS-AIH. But the
important question currently discussed in literature is if patients need to be treated with steroids
or immediately screened for liver transplantation as high corticosteroids before treatment can
cause high risk of infections after transplantation. Was liver transplantation evaluated as an
option for these patients?
7) Treatment effect was evaluated after 3 days. This is a very short period in comparison to the
available literature who advise to evaluate treatment between 7-14 days. Also I don’t understand
the decision to stop steroid treatment without evaluation for liver transplantation. If AIH and
AS-AIH if left untreated at all, the risk of mortality is very high.
8) Were patients also treated with azathioprine?
9) Disease relapse was reported in 1 patient. Without knowledge on steroid or treatment
withdrawal in all patients the interpretation of this data is difficult. Almost all AIH patients
develop relapse if treatment is stopped completely.
10) The authors have missed some relevant recent articles in the discussion including Anastasiou
et al 2018 Digestion; Zachou et al. 2019 Hepatology Research; Fujiwara et al. 2019 Liver
Transplantation; Biewenga et al. 2020 Liver Transplantation
Title: Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis
Version: 1 Date: 16 Nov 2020
Reviewer's report:
In this small retrospective cohort study 12 patients with AS-AIH are described on clinical
characteristics, histology and short term prognosis. No control group was included. AS-AIH is
a rare presentation of AIH which can be a challenge to diagnose and treat.
I have some comments regarding this study
1) Patients with underlying cirrhosis were excluded from the present study but form part of the
population of AIH that present with coagulopathy. How many patients with underlying cirrhosis
were excluded from the study? For treating physicians this is a relevant population.
2) How many patients presented with encephalopathy (AS-AIH with acute liver failure
according to a recent review by Rahim et al. Liver Transplantation 2019)
3) In the article is commented on the prevalence of seronegative AIH in AS-AIH. In the
introduction and discussion it is mentioned as a feature that occurs more often in AS-AIH. In
the present study it was around 25% of patients. No control group of AIH patients were included
and in chronic presentation up to 34% of seronegative AIH was reported according to reference
17. I’m not sure if it is occurring more often in AS-AIH patients
4) All liver biopsies were revised and only 3 patients had interface hepatitis. Interface hepatitis
is a hallmark feature of AIH and present in all scoring systems. Do you have an explanation why
interface hepatitis was present in so few patients?
5) Two patients with pour outcome are described were the interval between symptoms and
treatment initiation was 60 and 70 days. At what timepoint are de baseline characteristics of
these patients in table 1 taken? Is there an explanation for the diagnostic delay in these patients?
6) The authors state that treatment with steroids is not proven effective in AS-AIH. But the
important question currently discussed in literature is if patients need to be treated with steroids
or immediately screened for liver transplantation as high corticosteroids before treatment can
cause high risk of infections after transplantation. Was liver transplantation evaluated as an
option for these patients?
7) Treatment effect was evaluated after 3 days. This is a very short period in comparison to the
available literature who advise to evaluate treatment between 7-14 days. Also I don’t understand
the decision to stop steroid treatment without evaluation for liver transplantation. If AIH and
AS-AIH if left untreated at all, the risk of mortality is very high.
8) Were patients also treated with azathioprine?
9) Disease relapse was reported in 1 patient. Without knowledge on steroid or treatment
withdrawal in all patients the interpretation of this data is difficult. Almost all AIH patients
develop relapse if treatment is stopped completely.
10) The authors have missed some relevant recent articles in the discussion including Anastasiou
et al 2018 Digestion; Zachou et al. 2019 Hepatology Research; Fujiwara et al. 2019 Liver
Transplantation; Biewenga et al. 2020 Liver Transplantation
Please review this paper.
user
Title: Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis
Version: 1 Date: 16 Nov 2020
Reviewer's report:
In this small retrospective cohort study 12 patients with AS-AIH are described on clinical
characteristics, histology and short term prognosis. No control group was included. AS-AIH is
a rare presentation of AIH which can be a challenge to diagnose and treat.
I have some comments regarding this study
1) Patients with underlying cirrhosis were excluded from the present study but form part of the
population of AIH that present with coagulopathy. How many patients with underlying cirrhosis
were excluded from the study? For treating physicians this is a relevant population.
2) How many patients presented with encephalopathy (AS-AIH with acute liver failure
according to a recent review by Rahim et al. Liver Transplantation 2019)
3) In the article is commented on the prevalence of seronegative AIH in AS-AIH. In the
introduction and discussion it is mentioned as a feature that occurs more often in AS-AIH. In
the present study it was around 25% of patients. No control group of AIH patients were included
and in chronic presentation up to 34% of seronegative AIH was reported according to reference
17. I’m not sure if it is occurring more often in AS-AIH patients
4) All liver biopsies were revised and only 3 patients had interface hepatitis. Interface hepatitis
is a hallmark feature of AIH and present in all scoring systems. Do you have an explanation why
interface hepatitis was present in so few patients?
5) Two patients with pour outcome are described were the interval between symptoms and
treatment initiation was 60 and 70 days. At what timepoint are de baseline characteristics of
these patients in table 1 taken? Is there an explanation for the diagnostic delay in these patients?
6) The authors state that treatment with steroids is not proven effective in AS-AIH. But the
important question currently discussed in literature is if patients need to be treated with steroids
or immediately screened for liver transplantation as high corticosteroids before treatment can
cause high risk of infections after transplantation. Was liver transplantation evaluated as an
option for these patients?
7) Treatment effect was evaluated after 3 days. This is a very short period in comparison to the
available literature who advise to evaluate treatment between 7-14 days. Also I don’t understand
the decision to stop steroid treatment without evaluation for liver transplantation. If AIH and
AS-AIH if left untreated at all, the risk of mortality is very high.
8) Were patients also treated with azathioprine?
9) Disease relapse was reported in 1 patient. Without knowledge on steroid or treatment
withdrawal in all patients the interpretation of this data is difficult. Almost all AIH patients
develop relapse if treatment is stopped completely.
10) The authors have missed some relevant recent articles in the discussion including Anastasiou
et al 2018 Digestion; Zachou et al. 2019 Hepatology Research; Fujiwara et al. 2019 Liver
Transplantation; Biewenga et al. 2020 Liver Transplantation
assistant