Title: ICG-r15 Predicts Esophageal Varices in Compensated Liver Cirrhosis: A Noninvasive
Approach
Version: 0 Date: 05 Apr 2024
Reviewer's report:
The present study assesses the role of ICG retention test to predict risky EV in a mainly HBV
cirrhotic population. The study is interesting, it has a nice sample size though analysis and
interpretation deserve further clarification and discussion. My main comments:
- All non-invasive tests to predict either CSPH or L/M EV are not perfect and even having AUC
around 0.8 they must be proposed not as a unique cut-off test but a multiple risk tools to identify
or exclude with a high degree of success the event of interest. In this case the major endpoint to
exclude is to identify or exclude (with a very high NPV) the presence of risky varices. Therefore,
the approach of a simple cut-off is not good to identify patients at risk or not; many patients in
both sides of the cut-off are misclassified, and importantly, we cannot miss those with large EV.
I propose to select 2 cut-offs as previously done in many many similar studies, mainly oriented
ad ruling out those with very high probability of not having large EV. The analysis of the model
must present different potential cut-offs to rule in/rule out the presence of EV. A 2 cut-offs with
high certainty, while patients falling in the grey zone will inevitably need to undergo endoscopy.
Otherwise, as the results are presented have little applicability.
- Results: statistical analysis and assessment of the models is poor, only comparing predictors
individually. If I have correctly understood Table 2 presents a MV variable including all potential
predictors for EV, but this resulting model is not tested.... It must be done. And different
combined models (2, 3 or variables) should be presented and discussed so as to select the most
efficient and parsimonious model to identify or discard risky varices. This is mandatory and
would be really interesting to refine the test; platelets look like a good element to be combined
with. In the setting of predicting PHT and EH has been largely shown that a unique predictor is
not useful and the combination of 2 or three is always better (for example, plat/spleen/stiffness).
- Liver stiffness performance must be shown and included in the MV analysis along with ICG
and other potential markers. Makes no sense to exclude the current standard screening tool from
this analysis. Its performance in the cohort must be shown and compared to ICG and others. A
MV or combined stepped approach (with other tests) must be explored which potentially adds
to the diagnostic performance of the test.
- After selecting potential models (ICG with others or whatever) cut-offs to rule in or rule out EV
and the applicability of the model must be presented. Therefore, it must be compared to Baveno
VI criteria to rule out EV (Fibroscan <20 and Platelets>150) and many others reported elsewhere
(liver stiffness/plateletl/spleen size). Net reclassification index (or similar) as compared to other
tests must be provided as well as the number of potential of endoscopies to be avoided.
- ICG test is presented as a non-invasive test while an intravenous access is needed, it needs time
to stabilize ad several measurements must be done... Not so easy! Authors could discuss it as
a limitation and define costs of the procedure as compared to others. The advantages over new
potential screening tools (spleen stiffness) must be commented on.
- Platelets: its real AUC is 0.76 (the complementary of 0.24). There’s a problem in the way the
variable is coded in the model that it shows an inverted curve in the AUROC plot. Please correct.
Title: ICG-r15 Predicts Esophageal Varices in Compensated Liver Cirrhosis: A Noninvasive
Approach
Version: 0 Date: 05 Apr 2024
Reviewer's report:
The present study assesses the role of ICG retention test to predict risky EV in a mainly HBV
cirrhotic population. The study is interesting, it has a nice sample size though analysis and
interpretation deserve further clarification and discussion. My main comments:
- All non-invasive tests to predict either CSPH or L/M EV are not perfect and even having AUC
around 0.8 they must be proposed not as a unique cut-off test but a multiple risk tools to identify
or exclude with a high degree of success the event of interest. In this case the major endpoint to
exclude is to identify or exclude (with a very high NPV) the presence of risky varices. Therefore,
the approach of a simple cut-off is not good to identify patients at risk or not; many patients in
both sides of the cut-off are misclassified, and importantly, we cannot miss those with large EV.
I propose to select 2 cut-offs as previously done in many many similar studies, mainly oriented
ad ruling out those with very high probability of not having large EV. The analysis of the model
must present different potential cut-offs to rule in/rule out the presence of EV. A 2 cut-offs with
high certainty, while patients falling in the grey zone will inevitably need to undergo endoscopy.
Otherwise, as the results are presented have little applicability.
- Results: statistical analysis and assessment of the models is poor, only comparing predictors
individually. If I have correctly understood Table 2 presents a MV variable including all potential
predictors for EV, but this resulting model is not tested.... It must be done. And different
combined models (2, 3 or variables) should be presented and discussed so as to select the most
efficient and parsimonious model to identify or discard risky varices. This is mandatory and
would be really interesting to refine the test; platelets look like a good element to be combined
with. In the setting of predicting PHT and EH has been largely shown that a unique predictor is
not useful and the combination of 2 or three is always better (for example, plat/spleen/stiffness).
- Liver stiffness performance must be shown and included in the MV analysis along with ICG
and other potential markers. Makes no sense to exclude the current standard screening tool from
this analysis. Its performance in the cohort must be shown and compared to ICG and others. A
MV or combined stepped approach (with other tests) must be explored which potentially adds
to the diagnostic performance of the test.
- After selecting potential models (ICG with others or whatever) cut-offs to rule in or rule out EV
and the applicability of the model must be presented. Therefore, it must be compared to Baveno
VI criteria to rule out EV (Fibroscan <20 and Platelets>150) and many others reported elsewhere
(liver stiffness/plateletl/spleen size). Net reclassification index (or similar) as compared to other
tests must be provided as well as the number of potential of endoscopies to be avoided.
- ICG test is presented as a non-invasive test while an intravenous access is needed, it needs time
to stabilize ad several measurements must be done... Not so easy! Authors could discuss it as
a limitation and define costs of the procedure as compared to others. The advantages over new
potential screening tools (spleen stiffness) must be commented on.
- Platelets: its real AUC is 0.76 (the complementary of 0.24). There’s a problem in the way the
variable is coded in the model that it shows an inverted curve in the AUROC plot. Please correct.
Please review this paper.
user
Title: ICG-r15 Predicts Esophageal Varices in Compensated Liver Cirrhosis: A Noninvasive
Approach
Version: 0 Date: 05 Apr 2024
Reviewer's report:
The present study assesses the role of ICG retention test to predict risky EV in a mainly HBV
cirrhotic population. The study is interesting, it has a nice sample size though analysis and
interpretation deserve further clarification and discussion. My main comments:
- All non-invasive tests to predict either CSPH or L/M EV are not perfect and even having AUC
around 0.8 they must be proposed not as a unique cut-off test but a multiple risk tools to identify
or exclude with a high degree of success the event of interest. In this case the major endpoint to
exclude is to identify or exclude (with a very high NPV) the presence of risky varices. Therefore,
the approach of a simple cut-off is not good to identify patients at risk or not; many patients in
both sides of the cut-off are misclassified, and importantly, we cannot miss those with large EV.
I propose to select 2 cut-offs as previously done in many many similar studies, mainly oriented
ad ruling out those with very high probability of not having large EV. The analysis of the model
must present different potential cut-offs to rule in/rule out the presence of EV. A 2 cut-offs with
high certainty, while patients falling in the grey zone will inevitably need to undergo endoscopy.
Otherwise, as the results are presented have little applicability.
- Results: statistical analysis and assessment of the models is poor, only comparing predictors
individually. If I have correctly understood Table 2 presents a MV variable including all potential
predictors for EV, but this resulting model is not tested.... It must be done. And different
combined models (2, 3 or variables) should be presented and discussed so as to select the most
efficient and parsimonious model to identify or discard risky varices. This is mandatory and
would be really interesting to refine the test; platelets look like a good element to be combined
with. In the setting of predicting PHT and EH has been largely shown that a unique predictor is
not useful and the combination of 2 or three is always better (for example, plat/spleen/stiffness).
- Liver stiffness performance must be shown and included in the MV analysis along with ICG
and other potential markers. Makes no sense to exclude the current standard screening tool from
this analysis. Its performance in the cohort must be shown and compared to ICG and others. A
MV or combined stepped approach (with other tests) must be explored which potentially adds
to the diagnostic performance of the test.
- After selecting potential models (ICG with others or whatever) cut-offs to rule in or rule out EV
and the applicability of the model must be presented. Therefore, it must be compared to Baveno
VI criteria to rule out EV (Fibroscan <20 and Platelets>150) and many others reported elsewhere
(liver stiffness/plateletl/spleen size). Net reclassification index (or similar) as compared to other
tests must be provided as well as the number of potential of endoscopies to be avoided.
- ICG test is presented as a non-invasive test while an intravenous access is needed, it needs time
to stabilize ad several measurements must be done... Not so easy! Authors could discuss it as
a limitation and define costs of the procedure as compared to others. The advantages over new
potential screening tools (spleen stiffness) must be commented on.
- Platelets: its real AUC is 0.76 (the complementary of 0.24). There’s a problem in the way the
variable is coded in the model that it shows an inverted curve in the AUROC plot. Please correct.
assistant