Title: Treatment and outcome of hepatorenal syndrome in Japan: A retrospective cohort study
using a national inpatient database
Version: 2 Date: 06 Apr 2023
Reviewer's report:
Authors reported a very important epidemiological study of HRS using a national inpatient
database of Japan. I found this manuscript deserves merits to be published, however, several
comments needs to be answered before it is accepted.
* The most important problem with this study is the definition of HRS. It looks like authors
defines HRS by ICD-10 codes during hospitalization, is it correct? If it is so, this "HRS" includes
many cases with acute kidney injury (AKI) other than HRS.  Although authors only touched the
definition of HRS in limitation section, I urge them to discuss more on this.
* In line with above comment, in this study, they show that Child-Pugh class A & B accounted
for around  20% among "HRS" cases, which  cannot be true. As you know, most cases with HRS
show C-P class C with only a few cases with class B in cases with definite HRS.
I strongly suggest that C-P class A (&B) cases should be excluded from HRS.
* Most cases with HRS should have significant portal hypertension. Authors may disclose the
information on prevalence/severity of portal hypertension.
*  I wonder if etiology of liver cirrhosis should includes alcoholic, since alcoholic cirrhosis is
the main etiology for HRS in US & Europe.
* The statistical analyses in Table 2 may misleads readers, such as albumin/vasoconstrictor
use and  worse prognosis (death/liver transplant) was causal relationship (The nature of the
study design should preclude causal relationship, but since authors dare to  compare using
statistical analyses, authors should tell the readers its meanings). Since authors discussed the
underuse of specific/intensive treatment in the DIscussion, authors should discuss much more
on  interpretation of the result of these analyses, and show more data if available or from other
studies, which underscores the authors argument of more  use of intensive treatment (albumin/
vasopressin/noradrenaline).
Title: Treatment and outcome of hepatorenal syndrome in Japan: A retrospective cohort study
using a national inpatient database
Version: 2 Date: 06 Apr 2023
Reviewer's report:
Authors reported a very important epidemiological study of HRS using a national inpatient
database of Japan. I found this manuscript deserves merits to be published, however, several
comments needs to be answered before it is accepted.
* The most important problem with this study is the definition of HRS. It looks like authors
defines HRS by ICD-10 codes during hospitalization, is it correct? If it is so, this "HRS" includes
many cases with acute kidney injury (AKI) other than HRS.  Although authors only touched the
definition of HRS in limitation section, I urge them to discuss more on this.
* In line with above comment, in this study, they show that Child-Pugh class A & B accounted
for around  20% among "HRS" cases, which  cannot be true. As you know, most cases with HRS
show C-P class C with only a few cases with class B in cases with definite HRS.
I strongly suggest that C-P class A (&B) cases should be excluded from HRS.
* Most cases with HRS should have significant portal hypertension. Authors may disclose the
information on prevalence/severity of portal hypertension.
*  I wonder if etiology of liver cirrhosis should includes alcoholic, since alcoholic cirrhosis is
the main etiology for HRS in US & Europe.
* The statistical analyses in Table 2 may misleads readers, such as albumin/vasoconstrictor
use and  worse prognosis (death/liver transplant) was causal relationship (The nature of the
study design should preclude causal relationship, but since authors dare to  compare using
statistical analyses, authors should tell the readers its meanings). Since authors discussed the
underuse of specific/intensive treatment in the DIscussion, authors should discuss much more
on  interpretation of the result of these analyses, and show more data if available or from other
studies, which underscores the authors argument of more  use of intensive treatment (albumin/
vasopressin/noradrenaline).
Please review this paper.
user
Title: Treatment and outcome of hepatorenal syndrome in Japan: A retrospective cohort study
using a national inpatient database
Version: 2 Date: 06 Apr 2023
Reviewer's report:
Authors reported a very important epidemiological study of HRS using a national inpatient
database of Japan. I found this manuscript deserves merits to be published, however, several
comments needs to be answered before it is accepted.
* The most important problem with this study is the definition of HRS. It looks like authors
defines HRS by ICD-10 codes during hospitalization, is it correct? If it is so, this "HRS" includes
many cases with acute kidney injury (AKI) other than HRS.  Although authors only touched the
definition of HRS in limitation section, I urge them to discuss more on this.
* In line with above comment, in this study, they show that Child-Pugh class A & B accounted
for around  20% among "HRS" cases, which  cannot be true. As you know, most cases with HRS
show C-P class C with only a few cases with class B in cases with definite HRS.
I strongly suggest that C-P class A (&B) cases should be excluded from HRS.
* Most cases with HRS should have significant portal hypertension. Authors may disclose the
information on prevalence/severity of portal hypertension.
*  I wonder if etiology of liver cirrhosis should includes alcoholic, since alcoholic cirrhosis is
the main etiology for HRS in US & Europe.
* The statistical analyses in Table 2 may misleads readers, such as albumin/vasoconstrictor
use and  worse prognosis (death/liver transplant) was causal relationship (The nature of the
study design should preclude causal relationship, but since authors dare to  compare using
statistical analyses, authors should tell the readers its meanings). Since authors discussed the
underuse of specific/intensive treatment in the DIscussion, authors should discuss much more
on  interpretation of the result of these analyses, and show more data if available or from other
studies, which underscores the authors argument of more  use of intensive treatment (albumin/
vasopressin/noradrenaline).
assistant