Title: Predictive Scoring Systems for In-hospital Mortality due to Acutely Decompensated Liver
Cirrhosis in Indonesia
Version: 4 Date: 25 Apr 2021
Reviewer:  Rafael Bañares
Reviewer's report:
Nababan S. et al report the results of a retrospective cohort study performed in hospitalized
cirrhotic patients due to acute decompensation in which predictors of mortality were evaluated
to develop an algorithm with predictive value for in-hospital mortality.
Authors have done a relevant effort to give answers to a relevant health problem not only in
Indonesia but also throughout the World
Major comments:
- The main limitation we found in this study is that the concept of ACLF, currently
used in all main hepatology units, is not incorporated in the analysis.  As proven by the
CANONIC consortium, and subsequently validated by several studies, ACLF consists in a
specific syndrome with  different pathophysiological mechanisms compared to the classic acute
decompensation of cirrhosis. The proinflammatory status and secondary immunodeficiency in
ACLF entails a higher mortality which increases progressively accordingly to the number of
organ failure. It is possible that many of the patients included in the cohort had ACLF.  Given the
value of ACLF as a prognostic marker,  to incorporate this analysis to the results is of paramount
importance. Similarly, the algorithm given by the authors should evaluate its applicability in
patients with ACLF and AD separately.
- Another important limitation of the study is that there were no patients treated by TIPS. Given
the high rate of patients hospitalized with variceal bleeding (70.95%), it is worth noting that
none of the patients were treated with TIPS. This is a major limitation given that TIPS placement
has proven to increase survival in this context. Authors should include in the discussion why
patients weren’t treated with TIPS (probable due to the resources available). Similarly, it would
be of interest if authors evaluated which patients fulfilled criteria for example for preemptive-
TIPS, in order to perform a secondary analysis excluding these patients who weren’t treated
with the current standard of care.
- In the analysis performed, the baseline liver function of patients included characterized by
a well validated score such as MELD is not included. Authors should include if there were
differences in the baseline MELD (if it is available) as well as in the MELD at hospitalization
in both groups (patients who survived and patients that died).
- The time when the algorithm should be applied must be clearly specified. Given the dynamics
of the bilirubin and serum creatinine (both included in the algorithm proposed) it would be of
interest if the authors evaluated how the algorithm performs when calculated in two separated
moments of the hospitalization. It is conceivable that the evaluation of dynamic changes in these
key parameters could increase its prognostic value. This has been similarly proven in the context
of ACLF, when applied in the third and seventh day of hospitalization.
- With the information given in the Methods segment, only patients with the three classic
forms of decompensation (hepatic encephalopathy, ascites and variceal bleeding) were included.
However,  in the subsequent analysis, infection was one of the main factors associated with
mortality. Authors should clarify if patients without the previously mentioned classic forms of
decompensation but with an episode of bacterial infection diagnosed at admission were also
included.
Minor comments:
- We found that the flowchart doesn’t give much information given the retrospective design of
the study. It could be omitted from the main results.
- Author could mention if the patients age could partially be a confounding factor because
patients over certain age weren’t admitted in the ICU.
Title: Predictive Scoring Systems for In-hospital Mortality due to Acutely Decompensated Liver
Cirrhosis in Indonesia
Version: 4 Date: 25 Apr 2021
Reviewer:  Rafael Bañares
Reviewer's report:
Nababan S. et al report the results of a retrospective cohort study performed in hospitalized
cirrhotic patients due to acute decompensation in which predictors of mortality were evaluated
to develop an algorithm with predictive value for in-hospital mortality.
Authors have done a relevant effort to give answers to a relevant health problem not only in
Indonesia but also throughout the World
Major comments:
- The main limitation we found in this study is that the concept of ACLF, currently
used in all main hepatology units, is not incorporated in the analysis.  As proven by the
CANONIC consortium, and subsequently validated by several studies, ACLF consists in a
specific syndrome with  different pathophysiological mechanisms compared to the classic acute
decompensation of cirrhosis. The proinflammatory status and secondary immunodeficiency in
ACLF entails a higher mortality which increases progressively accordingly to the number of
organ failure. It is possible that many of the patients included in the cohort had ACLF.  Given the
value of ACLF as a prognostic marker,  to incorporate this analysis to the results is of paramount
importance. Similarly, the algorithm given by the authors should evaluate its applicability in
patients with ACLF and AD separately.
- Another important limitation of the study is that there were no patients treated by TIPS. Given
the high rate of patients hospitalized with variceal bleeding (70.95%), it is worth noting that
none of the patients were treated with TIPS. This is a major limitation given that TIPS placement
has proven to increase survival in this context. Authors should include in the discussion why
patients weren’t treated with TIPS (probable due to the resources available). Similarly, it would
be of interest if authors evaluated which patients fulfilled criteria for example for preemptive-
TIPS, in order to perform a secondary analysis excluding these patients who weren’t treated
with the current standard of care.
- In the analysis performed, the baseline liver function of patients included characterized by
a well validated score such as MELD is not included. Authors should include if there were
differences in the baseline MELD (if it is available) as well as in the MELD at hospitalization
in both groups (patients who survived and patients that died).
- The time when the algorithm should be applied must be clearly specified. Given the dynamics
of the bilirubin and serum creatinine (both included in the algorithm proposed) it would be of
interest if the authors evaluated how the algorithm performs when calculated in two separated
moments of the hospitalization. It is conceivable that the evaluation of dynamic changes in these
key parameters could increase its prognostic value. This has been similarly proven in the context
of ACLF, when applied in the third and seventh day of hospitalization.
- With the information given in the Methods segment, only patients with the three classic
forms of decompensation (hepatic encephalopathy, ascites and variceal bleeding) were included.
However,  in the subsequent analysis, infection was one of the main factors associated with
mortality. Authors should clarify if patients without the previously mentioned classic forms of
decompensation but with an episode of bacterial infection diagnosed at admission were also
included.
Minor comments:
- We found that the flowchart doesn’t give much information given the retrospective design of
the study. It could be omitted from the main results.
- Author could mention if the patients age could partially be a confounding factor because
patients over certain age weren’t admitted in the ICU.
Please review this paper.
user
Title: Predictive Scoring Systems for In-hospital Mortality due to Acutely Decompensated Liver
Cirrhosis in Indonesia
Version: 4 Date: 25 Apr 2021
Reviewer:  Rafael Bañares
Reviewer's report:
Nababan S. et al report the results of a retrospective cohort study performed in hospitalized
cirrhotic patients due to acute decompensation in which predictors of mortality were evaluated
to develop an algorithm with predictive value for in-hospital mortality.
Authors have done a relevant effort to give answers to a relevant health problem not only in
Indonesia but also throughout the World
Major comments:
- The main limitation we found in this study is that the concept of ACLF, currently
used in all main hepatology units, is not incorporated in the analysis.  As proven by the
CANONIC consortium, and subsequently validated by several studies, ACLF consists in a
specific syndrome with  different pathophysiological mechanisms compared to the classic acute
decompensation of cirrhosis. The proinflammatory status and secondary immunodeficiency in
ACLF entails a higher mortality which increases progressively accordingly to the number of
organ failure. It is possible that many of the patients included in the cohort had ACLF.  Given the
value of ACLF as a prognostic marker,  to incorporate this analysis to the results is of paramount
importance. Similarly, the algorithm given by the authors should evaluate its applicability in
patients with ACLF and AD separately.
- Another important limitation of the study is that there were no patients treated by TIPS. Given
the high rate of patients hospitalized with variceal bleeding (70.95%), it is worth noting that
none of the patients were treated with TIPS. This is a major limitation given that TIPS placement
has proven to increase survival in this context. Authors should include in the discussion why
patients weren’t treated with TIPS (probable due to the resources available). Similarly, it would
be of interest if authors evaluated which patients fulfilled criteria for example for preemptive-
TIPS, in order to perform a secondary analysis excluding these patients who weren’t treated
with the current standard of care.
- In the analysis performed, the baseline liver function of patients included characterized by
a well validated score such as MELD is not included. Authors should include if there were
differences in the baseline MELD (if it is available) as well as in the MELD at hospitalization
in both groups (patients who survived and patients that died).
- The time when the algorithm should be applied must be clearly specified. Given the dynamics
of the bilirubin and serum creatinine (both included in the algorithm proposed) it would be of
interest if the authors evaluated how the algorithm performs when calculated in two separated
moments of the hospitalization. It is conceivable that the evaluation of dynamic changes in these
key parameters could increase its prognostic value. This has been similarly proven in the context
of ACLF, when applied in the third and seventh day of hospitalization.
- With the information given in the Methods segment, only patients with the three classic
forms of decompensation (hepatic encephalopathy, ascites and variceal bleeding) were included.
However,  in the subsequent analysis, infection was one of the main factors associated with
mortality. Authors should clarify if patients without the previously mentioned classic forms of
decompensation but with an episode of bacterial infection diagnosed at admission were also
included.
Minor comments:
- We found that the flowchart doesn’t give much information given the retrospective design of
the study. It could be omitted from the main results.
- Author could mention if the patients age could partially be a confounding factor because
patients over certain age weren’t admitted in the ICU.
assistant