Title: A GLIM-Defined Malnutrition-Based Model for Predicting Prognosis of Cirrhotic
Patients with Portal Hypertension Following TIPS Procedure
Version: 4 Date: 21 Jul 2024
Reviewer's report:
Thank you for asking me to review this very important topic. The authors describe the role of
GLIM for the diagnosis of malnutrition in patients with decompensated cirrhoss undergoing
TIPS.
1.  I have major concerns about the application of GLIM criteria in patients with decompensated
cirrhosis and  I hope the authors can clarify in detail. One of the phenotypic criteria was non-
volitional weight loss. How did the authors define this ? The authors collected data on 'recent
weight change'(Section 2.3 Data Collection), presumably to determine if the patients had non-
volitional weight loss. How recent is 'recent' - is it 6 months, 9 months, 1 year, etc. before
TIPS? GLIM criteria states either >5% in  6 months or  >10% in >6 months. Secondly, as
the authors alluded to, patient's body weight is affected by ascites and edema.   While the
authors described body weight adjustment based on presence of ascites based on Tandon P et
al. (reference 12), the authors will need to have data on volume status and amount of ascites at
the start to determine 'recent weight change'.  It does not seem that the authors have this data
available, if the comparator weight was taken long ago.
2. I am assuming BMIc was used to determine low BMI phenotypic criteria. What threshold did
the authors use for this study to determine if the patients had low BMIc ?
3.  The authors described the diagnostic criteria for sarcopaenia based on TPMT based on
reference 11. The authors then went to to describe criteria for TPMT in malnutrition. While
TPMT at the level of L3 is a widely described mode of diagnosis for sarcopaenia, it has never
been studied in discriminating mild, moderate and severe muscle loss. Kindly provide a reference
for using TPMT to support the threshold mentioned in the manuscript.
4. Based on  the reported methods, malnutrition can be diagnosed either by one of the phenotypic
criteria of either non-volitional weight loss, low BMIc or low muscle mass. Can the authors
report the proportion of patients diagnosed by each phenotypic criteria.
5. The authors reported collecting data on RFH-NPT. This was not reported anywhere in the
results of the manuscript. Kindly clarify.
. The authors randomly divided the study cohort into training and validation cohort. What
randomization methods/statistics/software did the authors use to ensure that the division was
truly random ?
7. Table 1 very confusing. There were 6 columns of which the first and last columns were patient
characteristics and p value. However, the 4 columns in the middle  were not properly labelled
and I am not able to determine which column refers to data for well nourished or malnourished
patients.
8. The authors use competing risk analysis to compute cumulative incidence of HE/severe
HE and multivariable analysis for independent risk factors for HE. It was clarified that death
was a competing event to HE but no mention about liver transplant. Therefore, the cumulative
incidence and multivariable analysis ar only valid if none of the patients had undergone liver
transplantation. Can the authors clarify ?
9. The authors use Kaplan-Meier analysis, which is not a competing risk method for computing
overall survival.  Similar to question 6, liver transplantation is and can be considered competing
risk to death.  Unless no patient had undergone liver transplantation in this study,  the analysis
is incorrect. I would like the authors to clarify this as well.
10. In the multivariable Cox-regression analysis for overall survival, both MELD and MELD-
Na scores were highly significant as independent predictor of overall survival. Model 1 was
supposed to include MELD score but the HR is missing from Table 3.
11. It is well known that indication for TIPS determine post-TIPS survival,  ascites being a poor
prognostic indictor (Membreno F et al., JGH 2005). Although Table 1 is not very clearly written,
it is also well known that patients with severe ascites are more sarcopaenic and malnourished
compared to patients with milder ascites or no ascites. This is also described in the text under
"Comparison of baseline characteristics of the study patients".  In the analysis for overall
survival, indication for TIPS was not included in either the uni- or multivariable analysis.  I am
curious why indication TIPS was not even considered for univariate analysis and whether the
authors would consider including it in the final multivariable model if significant at univariate
analysis.
11. Strangely, while ascites is not included in the analysis for overall survival, it is somehow
included as one of the variables in the normogram predicting survival.
Title: A GLIM-Defined Malnutrition-Based Model for Predicting Prognosis of Cirrhotic
Patients with Portal Hypertension Following TIPS Procedure
Version: 4 Date: 21 Jul 2024
Reviewer's report:
Thank you for asking me to review this very important topic. The authors describe the role of
GLIM for the diagnosis of malnutrition in patients with decompensated cirrhoss undergoing
TIPS.
1.  I have major concerns about the application of GLIM criteria in patients with decompensated
cirrhosis and  I hope the authors can clarify in detail. One of the phenotypic criteria was non-
volitional weight loss. How did the authors define this ? The authors collected data on 'recent
weight change'(Section 2.3 Data Collection), presumably to determine if the patients had non-
volitional weight loss. How recent is 'recent' - is it 6 months, 9 months, 1 year, etc. before
TIPS? GLIM criteria states either >5% in  6 months or  >10% in >6 months. Secondly, as
the authors alluded to, patient's body weight is affected by ascites and edema.   While the
authors described body weight adjustment based on presence of ascites based on Tandon P et
al. (reference 12), the authors will need to have data on volume status and amount of ascites at
the start to determine 'recent weight change'.  It does not seem that the authors have this data
available, if the comparator weight was taken long ago.
2. I am assuming BMIc was used to determine low BMI phenotypic criteria. What threshold did
the authors use for this study to determine if the patients had low BMIc ?
3.  The authors described the diagnostic criteria for sarcopaenia based on TPMT based on
reference 11. The authors then went to to describe criteria for TPMT in malnutrition. While
TPMT at the level of L3 is a widely described mode of diagnosis for sarcopaenia, it has never
been studied in discriminating mild, moderate and severe muscle loss. Kindly provide a reference
for using TPMT to support the threshold mentioned in the manuscript.
4. Based on  the reported methods, malnutrition can be diagnosed either by one of the phenotypic
criteria of either non-volitional weight loss, low BMIc or low muscle mass. Can the authors
report the proportion of patients diagnosed by each phenotypic criteria.
5. The authors reported collecting data on RFH-NPT. This was not reported anywhere in the
results of the manuscript. Kindly clarify.
. The authors randomly divided the study cohort into training and validation cohort. What
randomization methods/statistics/software did the authors use to ensure that the division was
truly random ?
7. Table 1 very confusing. There were 6 columns of which the first and last columns were patient
characteristics and p value. However, the 4 columns in the middle  were not properly labelled
and I am not able to determine which column refers to data for well nourished or malnourished
patients.
8. The authors use competing risk analysis to compute cumulative incidence of HE/severe
HE and multivariable analysis for independent risk factors for HE. It was clarified that death
was a competing event to HE but no mention about liver transplant. Therefore, the cumulative
incidence and multivariable analysis ar only valid if none of the patients had undergone liver
transplantation. Can the authors clarify ?
9. The authors use Kaplan-Meier analysis, which is not a competing risk method for computing
overall survival.  Similar to question 6, liver transplantation is and can be considered competing
risk to death.  Unless no patient had undergone liver transplantation in this study,  the analysis
is incorrect. I would like the authors to clarify this as well.
10. In the multivariable Cox-regression analysis for overall survival, both MELD and MELD-
Na scores were highly significant as independent predictor of overall survival. Model 1 was
supposed to include MELD score but the HR is missing from Table 3.
11. It is well known that indication for TIPS determine post-TIPS survival,  ascites being a poor
prognostic indictor (Membreno F et al., JGH 2005). Although Table 1 is not very clearly written,
it is also well known that patients with severe ascites are more sarcopaenic and malnourished
compared to patients with milder ascites or no ascites. This is also described in the text under
"Comparison of baseline characteristics of the study patients".  In the analysis for overall
survival, indication for TIPS was not included in either the uni- or multivariable analysis.  I am
curious why indication TIPS was not even considered for univariate analysis and whether the
authors would consider including it in the final multivariable model if significant at univariate
analysis.
11. Strangely, while ascites is not included in the analysis for overall survival, it is somehow
included as one of the variables in the normogram predicting survival.
Please review this paper.
user
Title: A GLIM-Defined Malnutrition-Based Model for Predicting Prognosis of Cirrhotic
Patients with Portal Hypertension Following TIPS Procedure
Version: 4 Date: 21 Jul 2024
Reviewer's report:
Thank you for asking me to review this very important topic. The authors describe the role of
GLIM for the diagnosis of malnutrition in patients with decompensated cirrhoss undergoing
TIPS.
1.  I have major concerns about the application of GLIM criteria in patients with decompensated
cirrhosis and  I hope the authors can clarify in detail. One of the phenotypic criteria was non-
volitional weight loss. How did the authors define this ? The authors collected data on 'recent
weight change'(Section 2.3 Data Collection), presumably to determine if the patients had non-
volitional weight loss. How recent is 'recent' - is it 6 months, 9 months, 1 year, etc. before
TIPS? GLIM criteria states either >5% in  6 months or  >10% in >6 months. Secondly, as
the authors alluded to, patient's body weight is affected by ascites and edema.   While the
authors described body weight adjustment based on presence of ascites based on Tandon P et
al. (reference 12), the authors will need to have data on volume status and amount of ascites at
the start to determine 'recent weight change'.  It does not seem that the authors have this data
available, if the comparator weight was taken long ago.
2. I am assuming BMIc was used to determine low BMI phenotypic criteria. What threshold did
the authors use for this study to determine if the patients had low BMIc ?
3.  The authors described the diagnostic criteria for sarcopaenia based on TPMT based on
reference 11. The authors then went to to describe criteria for TPMT in malnutrition. While
TPMT at the level of L3 is a widely described mode of diagnosis for sarcopaenia, it has never
been studied in discriminating mild, moderate and severe muscle loss. Kindly provide a reference
for using TPMT to support the threshold mentioned in the manuscript.
4. Based on  the reported methods, malnutrition can be diagnosed either by one of the phenotypic
criteria of either non-volitional weight loss, low BMIc or low muscle mass. Can the authors
report the proportion of patients diagnosed by each phenotypic criteria.
5. The authors reported collecting data on RFH-NPT. This was not reported anywhere in the
results of the manuscript. Kindly clarify.
. The authors randomly divided the study cohort into training and validation cohort. What
randomization methods/statistics/software did the authors use to ensure that the division was
truly random ?
7. Table 1 very confusing. There were 6 columns of which the first and last columns were patient
characteristics and p value. However, the 4 columns in the middle  were not properly labelled
and I am not able to determine which column refers to data for well nourished or malnourished
patients.
8. The authors use competing risk analysis to compute cumulative incidence of HE/severe
HE and multivariable analysis for independent risk factors for HE. It was clarified that death
was a competing event to HE but no mention about liver transplant. Therefore, the cumulative
incidence and multivariable analysis ar only valid if none of the patients had undergone liver
transplantation. Can the authors clarify ?
9. The authors use Kaplan-Meier analysis, which is not a competing risk method for computing
overall survival.  Similar to question 6, liver transplantation is and can be considered competing
risk to death.  Unless no patient had undergone liver transplantation in this study,  the analysis
is incorrect. I would like the authors to clarify this as well.
10. In the multivariable Cox-regression analysis for overall survival, both MELD and MELD-
Na scores were highly significant as independent predictor of overall survival. Model 1 was
supposed to include MELD score but the HR is missing from Table 3.
11. It is well known that indication for TIPS determine post-TIPS survival,  ascites being a poor
prognostic indictor (Membreno F et al., JGH 2005). Although Table 1 is not very clearly written,
it is also well known that patients with severe ascites are more sarcopaenic and malnourished
compared to patients with milder ascites or no ascites. This is also described in the text under
"Comparison of baseline characteristics of the study patients".  In the analysis for overall
survival, indication for TIPS was not included in either the uni- or multivariable analysis.  I am
curious why indication TIPS was not even considered for univariate analysis and whether the
authors would consider including it in the final multivariable model if significant at univariate
analysis.
11. Strangely, while ascites is not included in the analysis for overall survival, it is somehow
included as one of the variables in the normogram predicting survival.
assistant