Title: Management of hepatocellular carcinoma, an important cause of death in Japanese
autoimmune hepatitis patients
Version: 3 Date: 14 Feb 2024
Reviewer's report:
The study retrospectively analyzed the risk factors and prognosis of HCC in patients with AIH.
As already established in the other studies performed in  patients with viral and non viral liver
disease etiology , cirrhotic stage  was significantly associated with the risk of HCC development
in the multivariate analysis (OR 41,  p< 0.0001). The autoimmune etiology made difficult the
therapeutic management as immune checkpoint inhibitors were not used due to autoimmune
etiology and two of the three patients treated with molecular-targeted drugs discontinued the
treatment because of adverse events.
The interest of this study mainly relies on the poorly explored HCC occurrence in AIH patients
so far. However, there are important issues requiring attention.
- HCC cohort patient: of the 131 enrolled patients,  there were 44 patients with AIH/PBC
patients. The authors used the AIH revised score for the diagnosis of AIH and the Paris criteria
for the diagnosis of AIH/PBC overlap syndrome. A pivotal study of Czaja, demonstrated that
the simplified score has greater specificity and predictability for AIH than the revised original
system, and it more commonly excluded the diagnosis in other diseases with concurrent immune
features (DOI: 10.1002/hep.22513).  Importantly, in clinical practice, the simplified AIH score
has been validated in an AIH cohort including  AIH/PBC overlap patients, as previously reported
(doi: 10.1002/hep.22825.). It's therefore of significant importance to report the simplified AIH
scores of AIH and  AIH/PBC patients discussing this clinically relevant point and the validated
use of the simplified criteria in AIH/PBC overlap cases.
- It would be of significant interest to include matched control groups of pure PBC patients and
HCV/HBV patients to compare the rate of HCC occurence and clinical features of the different
etiologies.
-To further evaluate the characteristics of patients developing HCC, it is necessary describing
the treatment as well as treatment response according to established criteria (AASLD guidelines
DOI: 10.1002/hep.31065 ) .
-of the three HCC patients receiving molecular target therapy, one received sorafenib and one
lenvatinib. The third one?
Title: Management of hepatocellular carcinoma, an important cause of death in Japanese
autoimmune hepatitis patients
Version: 3 Date: 14 Feb 2024
Reviewer's report:
The study retrospectively analyzed the risk factors and prognosis of HCC in patients with AIH.
As already established in the other studies performed in  patients with viral and non viral liver
disease etiology , cirrhotic stage  was significantly associated with the risk of HCC development
in the multivariate analysis (OR 41,  p< 0.0001). The autoimmune etiology made difficult the
therapeutic management as immune checkpoint inhibitors were not used due to autoimmune
etiology and two of the three patients treated with molecular-targeted drugs discontinued the
treatment because of adverse events.
The interest of this study mainly relies on the poorly explored HCC occurrence in AIH patients
so far. However, there are important issues requiring attention.
- HCC cohort patient: of the 131 enrolled patients,  there were 44 patients with AIH/PBC
patients. The authors used the AIH revised score for the diagnosis of AIH and the Paris criteria
for the diagnosis of AIH/PBC overlap syndrome. A pivotal study of Czaja, demonstrated that
the simplified score has greater specificity and predictability for AIH than the revised original
system, and it more commonly excluded the diagnosis in other diseases with concurrent immune
features (DOI: 10.1002/hep.22513).  Importantly, in clinical practice, the simplified AIH score
has been validated in an AIH cohort including  AIH/PBC overlap patients, as previously reported
(doi: 10.1002/hep.22825.). It's therefore of significant importance to report the simplified AIH
scores of AIH and  AIH/PBC patients discussing this clinically relevant point and the validated
use of the simplified criteria in AIH/PBC overlap cases.
- It would be of significant interest to include matched control groups of pure PBC patients and
HCV/HBV patients to compare the rate of HCC occurence and clinical features of the different
etiologies.
-To further evaluate the characteristics of patients developing HCC, it is necessary describing
the treatment as well as treatment response according to established criteria (AASLD guidelines
DOI: 10.1002/hep.31065 ) .
-of the three HCC patients receiving molecular target therapy, one received sorafenib and one
lenvatinib. The third one?
Please review this paper.
user
Title: Management of hepatocellular carcinoma, an important cause of death in Japanese
autoimmune hepatitis patients
Version: 3 Date: 14 Feb 2024
Reviewer's report:
The study retrospectively analyzed the risk factors and prognosis of HCC in patients with AIH.
As already established in the other studies performed in  patients with viral and non viral liver
disease etiology , cirrhotic stage  was significantly associated with the risk of HCC development
in the multivariate analysis (OR 41,  p< 0.0001). The autoimmune etiology made difficult the
therapeutic management as immune checkpoint inhibitors were not used due to autoimmune
etiology and two of the three patients treated with molecular-targeted drugs discontinued the
treatment because of adverse events.
The interest of this study mainly relies on the poorly explored HCC occurrence in AIH patients
so far. However, there are important issues requiring attention.
- HCC cohort patient: of the 131 enrolled patients,  there were 44 patients with AIH/PBC
patients. The authors used the AIH revised score for the diagnosis of AIH and the Paris criteria
for the diagnosis of AIH/PBC overlap syndrome. A pivotal study of Czaja, demonstrated that
the simplified score has greater specificity and predictability for AIH than the revised original
system, and it more commonly excluded the diagnosis in other diseases with concurrent immune
features (DOI: 10.1002/hep.22513).  Importantly, in clinical practice, the simplified AIH score
has been validated in an AIH cohort including  AIH/PBC overlap patients, as previously reported
(doi: 10.1002/hep.22825.). It's therefore of significant importance to report the simplified AIH
scores of AIH and  AIH/PBC patients discussing this clinically relevant point and the validated
use of the simplified criteria in AIH/PBC overlap cases.
- It would be of significant interest to include matched control groups of pure PBC patients and
HCV/HBV patients to compare the rate of HCC occurence and clinical features of the different
etiologies.
-To further evaluate the characteristics of patients developing HCC, it is necessary describing
the treatment as well as treatment response according to established criteria (AASLD guidelines
DOI: 10.1002/hep.31065 ) .
-of the three HCC patients receiving molecular target therapy, one received sorafenib and one
lenvatinib. The third one?
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