Title: Comparison of the efficacy and safety between rivaroxaban and dabigatran in the
treatment of acute portal vein thrombosis in cirrhosis
Version: 2 Date: 07 May 2023
Reviewer's report:
In the study by Haonon Zhou et al, the authors retrospectively evaluated 94 consecutive cirrhosis
patients with acute portal vein thrombosis from January 2020 to December 2021 and compared
anticoagulation with rivaroxaban (rivaroxaban group) or dabigatran (dabigatran group). The
diagnosis of acute PVT was confirmed by CT scan imaging in nearly all patients. The severity
of liver cirrhosis was assessed using Child-Pugh score and Model for End-Stage Liver Disease
(MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion),
bleedings, and survival. The log-rank test was used to compare Kaplan-Meier distributions of
time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios
(HRs) with 95% confidence intervals (CIs).
From a total of 94 patients included, 52 patients (55%) accepted rivaroxaban and 42 (45%) with
dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There
was no significant difference in complete recanalization, partial recanalization, and persistent
occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI
1.036-1.311, p=0.011) was independent predictors of complete recanalization. The Child-
Pugh score (p=0.001) was significantly improved in both two groups after anticoagulation,
respectively.However, there was no difference between the two groups. The probability of
survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p= 0.830).  Major
bleedingswere reported in 3 patients (6%)in rivaroxaban group and 1 patient (2%) in dabigatran
group (p=0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five
(12%) from dabigatran group (p=0.691).
The authors concluded that the efficacy and safety were comparable between rivaroxaban and
dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis.
Major comments
Methods:
1. Why wasn´t apixaban which has more predictable anticoagulant effect in patients with
cirrhosis not considered for anticoagulant therapy?
2. Exclusion criteria: No mention of severe thrombocytopenia (Plaletet count <40,000 10^9/L.
Did any of the patients have these values ?
3. What was the rationale for exclusion of isolated superior mesenteric vein thrombosis?
Recanalization could be assessed by CT as the vast majority of patients had baseline CT imaging.
4. What about worsening extension and degree of luminal occlusion of PVT during follow-up?
This is not mentioned but is a clinical reality even in patients on anticoagulation and these are
potential candidates for TIPS placement.
5. There is no mention of endoscopic screening of the patients for esophageal and / or gastric
varices which is in my opinion essential to avoid adverse events.
6. Was primary / secondary prophylaxis of variceal bleeding instituted prior to starting
anticoagulation? Again, in my opinion, these two steps are crucial for improving safety of
anticoagulant therapy to decrease bleeding risk in patients with underlying portal hypertension.
7. In statistical analysis, Mann-Whitney test is ideally applicable only for continuous variables
with non normal distribution which are expressed as median, while Student´s t test is ideal for
continuous variables with normal distribution.
8. What test was used for determining HRs? This should be mentioned just as it has been
mentioned in the abstract.
9. What test was used for multivariate analysis and what criteria were used for selecting the
variables in terms of level of significance?
Results:
10. Please place the absolute number of patients after percentage with thrombocytopenia. What
was the cut off for definition of thrombocytopenia ? This should be mentioned in the methods
section. Any patients excluded for anticoagulant therapy due to severe thrombocytopenia?
11. There seems to be some discrepancy regarding the duration of anticoagulant therapy which is
15 and 18 months and duration of follow up which is 5,5 and 5 months. Please rectify / comment.
The survival curves suggest longer follow-up periods than those mentioned.
12. Follow-up in my opinion should be considered from the time of diagnosis of PVT.
13. In table 1. There should be mention of percentage of patients on beta blockers / prior banding
for prophylaxis of variceal bleeding.
14. Please place absolute values after the percentages of complete and partial recanalization of
PVT in both groups.
15. Please place percentage before absolute number of patients with occlusive PVT. From
clinical experience this value is quite high and may reflect bias in patient selection for the study.
16. There were only 5 deaths and therefore, it does not make any clinical sense to do multivariate
analysis for predictors of death.
Discussion
17. The discussion section is long. It would be sensible to start this section with a summary of
the main findings of the study.
18. A deeper discussion into D-dimers as predictors of imbalance in hemostasis mechanisms
and predictors of PVT recanalization should be added.
Conclusion:
19. The last two sentences are redundant. The conclusion should highlight the potential utility
of levels of D Dimers in predicting PVT recanalization.
Minor comments.
20. Revision of the manuscript by a native english speaker is recommended as there are quite a
few phrase construction glitches in the manuscript.
Title: Comparison of the efficacy and safety between rivaroxaban and dabigatran in the
treatment of acute portal vein thrombosis in cirrhosis
Version: 2 Date: 07 May 2023
Reviewer's report:
In the study by Haonon Zhou et al, the authors retrospectively evaluated 94 consecutive cirrhosis
patients with acute portal vein thrombosis from January 2020 to December 2021 and compared
anticoagulation with rivaroxaban (rivaroxaban group) or dabigatran (dabigatran group). The
diagnosis of acute PVT was confirmed by CT scan imaging in nearly all patients. The severity
of liver cirrhosis was assessed using Child-Pugh score and Model for End-Stage Liver Disease
(MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion),
bleedings, and survival. The log-rank test was used to compare Kaplan-Meier distributions of
time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios
(HRs) with 95% confidence intervals (CIs).
From a total of 94 patients included, 52 patients (55%) accepted rivaroxaban and 42 (45%) with
dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There
was no significant difference in complete recanalization, partial recanalization, and persistent
occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI
1.036-1.311, p=0.011) was independent predictors of complete recanalization. The Child-
Pugh score (p=0.001) was significantly improved in both two groups after anticoagulation,
respectively.However, there was no difference between the two groups. The probability of
survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p= 0.830).  Major
bleedingswere reported in 3 patients (6%)in rivaroxaban group and 1 patient (2%) in dabigatran
group (p=0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five
(12%) from dabigatran group (p=0.691).
The authors concluded that the efficacy and safety were comparable between rivaroxaban and
dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis.
Major comments
Methods:
1. Why wasn´t apixaban which has more predictable anticoagulant effect in patients with
cirrhosis not considered for anticoagulant therapy?
2. Exclusion criteria: No mention of severe thrombocytopenia (Plaletet count <40,000 10^9/L.
Did any of the patients have these values ?
3. What was the rationale for exclusion of isolated superior mesenteric vein thrombosis?
Recanalization could be assessed by CT as the vast majority of patients had baseline CT imaging.
4. What about worsening extension and degree of luminal occlusion of PVT during follow-up?
This is not mentioned but is a clinical reality even in patients on anticoagulation and these are
potential candidates for TIPS placement.
5. There is no mention of endoscopic screening of the patients for esophageal and / or gastric
varices which is in my opinion essential to avoid adverse events.
6. Was primary / secondary prophylaxis of variceal bleeding instituted prior to starting
anticoagulation? Again, in my opinion, these two steps are crucial for improving safety of
anticoagulant therapy to decrease bleeding risk in patients with underlying portal hypertension.
7. In statistical analysis, Mann-Whitney test is ideally applicable only for continuous variables
with non normal distribution which are expressed as median, while Student´s t test is ideal for
continuous variables with normal distribution.
8. What test was used for determining HRs? This should be mentioned just as it has been
mentioned in the abstract.
9. What test was used for multivariate analysis and what criteria were used for selecting the
variables in terms of level of significance?
Results:
10. Please place the absolute number of patients after percentage with thrombocytopenia. What
was the cut off for definition of thrombocytopenia ? This should be mentioned in the methods
section. Any patients excluded for anticoagulant therapy due to severe thrombocytopenia?
11. There seems to be some discrepancy regarding the duration of anticoagulant therapy which is
15 and 18 months and duration of follow up which is 5,5 and 5 months. Please rectify / comment.
The survival curves suggest longer follow-up periods than those mentioned.
12. Follow-up in my opinion should be considered from the time of diagnosis of PVT.
13. In table 1. There should be mention of percentage of patients on beta blockers / prior banding
for prophylaxis of variceal bleeding.
14. Please place absolute values after the percentages of complete and partial recanalization of
PVT in both groups.
15. Please place percentage before absolute number of patients with occlusive PVT. From
clinical experience this value is quite high and may reflect bias in patient selection for the study.
16. There were only 5 deaths and therefore, it does not make any clinical sense to do multivariate
analysis for predictors of death.
Discussion
17. The discussion section is long. It would be sensible to start this section with a summary of
the main findings of the study.
18. A deeper discussion into D-dimers as predictors of imbalance in hemostasis mechanisms
and predictors of PVT recanalization should be added.
Conclusion:
19. The last two sentences are redundant. The conclusion should highlight the potential utility
of levels of D Dimers in predicting PVT recanalization.
Minor comments.
20. Revision of the manuscript by a native english speaker is recommended as there are quite a
few phrase construction glitches in the manuscript.
Please review this paper.
user
Title: Comparison of the efficacy and safety between rivaroxaban and dabigatran in the
treatment of acute portal vein thrombosis in cirrhosis
Version: 2 Date: 07 May 2023
Reviewer's report:
In the study by Haonon Zhou et al, the authors retrospectively evaluated 94 consecutive cirrhosis
patients with acute portal vein thrombosis from January 2020 to December 2021 and compared
anticoagulation with rivaroxaban (rivaroxaban group) or dabigatran (dabigatran group). The
diagnosis of acute PVT was confirmed by CT scan imaging in nearly all patients. The severity
of liver cirrhosis was assessed using Child-Pugh score and Model for End-Stage Liver Disease
(MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion),
bleedings, and survival. The log-rank test was used to compare Kaplan-Meier distributions of
time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios
(HRs) with 95% confidence intervals (CIs).
From a total of 94 patients included, 52 patients (55%) accepted rivaroxaban and 42 (45%) with
dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There
was no significant difference in complete recanalization, partial recanalization, and persistent
occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI
1.036-1.311, p=0.011) was independent predictors of complete recanalization. The Child-
Pugh score (p=0.001) was significantly improved in both two groups after anticoagulation,
respectively.However, there was no difference between the two groups. The probability of
survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p= 0.830).  Major
bleedingswere reported in 3 patients (6%)in rivaroxaban group and 1 patient (2%) in dabigatran
group (p=0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five
(12%) from dabigatran group (p=0.691).
The authors concluded that the efficacy and safety were comparable between rivaroxaban and
dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis.
Major comments
Methods:
1. Why wasn´t apixaban which has more predictable anticoagulant effect in patients with
cirrhosis not considered for anticoagulant therapy?
2. Exclusion criteria: No mention of severe thrombocytopenia (Plaletet count <40,000 10^9/L.
Did any of the patients have these values ?
3. What was the rationale for exclusion of isolated superior mesenteric vein thrombosis?
Recanalization could be assessed by CT as the vast majority of patients had baseline CT imaging.
4. What about worsening extension and degree of luminal occlusion of PVT during follow-up?
This is not mentioned but is a clinical reality even in patients on anticoagulation and these are
potential candidates for TIPS placement.
5. There is no mention of endoscopic screening of the patients for esophageal and / or gastric
varices which is in my opinion essential to avoid adverse events.
6. Was primary / secondary prophylaxis of variceal bleeding instituted prior to starting
anticoagulation? Again, in my opinion, these two steps are crucial for improving safety of
anticoagulant therapy to decrease bleeding risk in patients with underlying portal hypertension.
7. In statistical analysis, Mann-Whitney test is ideally applicable only for continuous variables
with non normal distribution which are expressed as median, while Student´s t test is ideal for
continuous variables with normal distribution.
8. What test was used for determining HRs? This should be mentioned just as it has been
mentioned in the abstract.
9. What test was used for multivariate analysis and what criteria were used for selecting the
variables in terms of level of significance?
Results:
10. Please place the absolute number of patients after percentage with thrombocytopenia. What
was the cut off for definition of thrombocytopenia ? This should be mentioned in the methods
section. Any patients excluded for anticoagulant therapy due to severe thrombocytopenia?
11. There seems to be some discrepancy regarding the duration of anticoagulant therapy which is
15 and 18 months and duration of follow up which is 5,5 and 5 months. Please rectify / comment.
The survival curves suggest longer follow-up periods than those mentioned.
12. Follow-up in my opinion should be considered from the time of diagnosis of PVT.
13. In table 1. There should be mention of percentage of patients on beta blockers / prior banding
for prophylaxis of variceal bleeding.
14. Please place absolute values after the percentages of complete and partial recanalization of
PVT in both groups.
15. Please place percentage before absolute number of patients with occlusive PVT. From
clinical experience this value is quite high and may reflect bias in patient selection for the study.
16. There were only 5 deaths and therefore, it does not make any clinical sense to do multivariate
analysis for predictors of death.
Discussion
17. The discussion section is long. It would be sensible to start this section with a summary of
the main findings of the study.
18. A deeper discussion into D-dimers as predictors of imbalance in hemostasis mechanisms
and predictors of PVT recanalization should be added.
Conclusion:
19. The last two sentences are redundant. The conclusion should highlight the potential utility
of levels of D Dimers in predicting PVT recanalization.
Minor comments.
20. Revision of the manuscript by a native english speaker is recommended as there are quite a
few phrase construction glitches in the manuscript.
assistant