Title: Portal Vein Thrombosis and Esophageal-Gastric Variceal Bleeding in Cirrhosis: Shared
Risk Factors and Causal Relationship
Version: 3 Date: 28 May 2025
Reviewer's report:
The manuscript presents interesting and potentially valuable research on PVT and EVB in
cirrhosis. However, several important clarifications and additions are necessary to strengthen
the methodological rigor, contextual relevance, and accuracy of the findings before it can be
considered suitable for publication.
1.  In the natural history of cirrhosis, the presence of pre-existing esophageal/gastric varices
(particularly their size and red wale signs) is a paramount risk factor for first bleeding. Crucially,
whether a patient is on established primary prophylaxis (e.g., non-selective beta-blockers or
endoscopic variceal ligation) significantly modifies this risk. The current analysis appears to lack
data on previous endoscopic findings (varices: yes/no, grade, features) and primary prophylaxis
status (yes/no, type). This omission is a significant limitation. We strongly recommend the
authors supplement their dataset and analysis to include these essential variables.
Specifically:
Report the proportion of patients with known pre-existing varices prior to the index event/study
period.
Report the proportion of patients receiving primary prophylaxis and the type used (NSBB, EVL,
combination, none).
Include these factors (previous varices, primary prophylaxis status) as covariates in multivariate
analyses of EGVB risk factors. Discuss how their inclusion (or absence in the current analysis)
impacts the interpretation of the identified risk factors. Failure to account for these well-
established modifiers substantially weakens the conclusions regarding novel or other risk
factors.
2. The manuscript utilizes a classification for Portal Vein Thrombosis (PVT) (e.g., partial/
complete, acute/chronic, extent). However, it does not explicitly state which specific
classification criteria or definitions were applied at the study center. To ensure clarity and
reproducibility, please explicitly reference the specific PVT classification standard used in your
center (e.g., Yerdel classification, European Association for the Study of the Liver (EASL)
guidelines definitions, American Association for the Study of Liver Diseases (AASLD) practice
guidance definitions, or an internally validated protocol).
3. On Page 5, Lines 96-97, the text states: " This study implemented three distinct patient
groupings to evaluate the relationships between clinical variables and outcomes" However, the
subsequent description (Lines 97-100) details only two distinct grouping methods.
Provide the missing description for the third grouping method  and ensure the results analysis
consistently reflects all three groupings mentioned.
Title: Portal Vein Thrombosis and Esophageal-Gastric Variceal Bleeding in Cirrhosis: Shared
Risk Factors and Causal Relationship
Version: 3 Date: 28 May 2025
Reviewer's report:
The manuscript presents interesting and potentially valuable research on PVT and EVB in
cirrhosis. However, several important clarifications and additions are necessary to strengthen
the methodological rigor, contextual relevance, and accuracy of the findings before it can be
considered suitable for publication.
1.  In the natural history of cirrhosis, the presence of pre-existing esophageal/gastric varices
(particularly their size and red wale signs) is a paramount risk factor for first bleeding. Crucially,
whether a patient is on established primary prophylaxis (e.g., non-selective beta-blockers or
endoscopic variceal ligation) significantly modifies this risk. The current analysis appears to lack
data on previous endoscopic findings (varices: yes/no, grade, features) and primary prophylaxis
status (yes/no, type). This omission is a significant limitation. We strongly recommend the
authors supplement their dataset and analysis to include these essential variables.
Specifically:
Report the proportion of patients with known pre-existing varices prior to the index event/study
period.
Report the proportion of patients receiving primary prophylaxis and the type used (NSBB, EVL,
combination, none).
Include these factors (previous varices, primary prophylaxis status) as covariates in multivariate
analyses of EGVB risk factors. Discuss how their inclusion (or absence in the current analysis)
impacts the interpretation of the identified risk factors. Failure to account for these well-
established modifiers substantially weakens the conclusions regarding novel or other risk
factors.
2. The manuscript utilizes a classification for Portal Vein Thrombosis (PVT) (e.g., partial/
complete, acute/chronic, extent). However, it does not explicitly state which specific
classification criteria or definitions were applied at the study center. To ensure clarity and
reproducibility, please explicitly reference the specific PVT classification standard used in your
center (e.g., Yerdel classification, European Association for the Study of the Liver (EASL)
guidelines definitions, American Association for the Study of Liver Diseases (AASLD) practice
guidance definitions, or an internally validated protocol).
3. On Page 5, Lines 96-97, the text states: " This study implemented three distinct patient
groupings to evaluate the relationships between clinical variables and outcomes" However, the
subsequent description (Lines 97-100) details only two distinct grouping methods.
Provide the missing description for the third grouping method  and ensure the results analysis
consistently reflects all three groupings mentioned.
Please review this paper.
user
Title: Portal Vein Thrombosis and Esophageal-Gastric Variceal Bleeding in Cirrhosis: Shared
Risk Factors and Causal Relationship
Version: 3 Date: 28 May 2025
Reviewer's report:
The manuscript presents interesting and potentially valuable research on PVT and EVB in
cirrhosis. However, several important clarifications and additions are necessary to strengthen
the methodological rigor, contextual relevance, and accuracy of the findings before it can be
considered suitable for publication.
1.  In the natural history of cirrhosis, the presence of pre-existing esophageal/gastric varices
(particularly their size and red wale signs) is a paramount risk factor for first bleeding. Crucially,
whether a patient is on established primary prophylaxis (e.g., non-selective beta-blockers or
endoscopic variceal ligation) significantly modifies this risk. The current analysis appears to lack
data on previous endoscopic findings (varices: yes/no, grade, features) and primary prophylaxis
status (yes/no, type). This omission is a significant limitation. We strongly recommend the
authors supplement their dataset and analysis to include these essential variables.
Specifically:
Report the proportion of patients with known pre-existing varices prior to the index event/study
period.
Report the proportion of patients receiving primary prophylaxis and the type used (NSBB, EVL,
combination, none).
Include these factors (previous varices, primary prophylaxis status) as covariates in multivariate
analyses of EGVB risk factors. Discuss how their inclusion (or absence in the current analysis)
impacts the interpretation of the identified risk factors. Failure to account for these well-
established modifiers substantially weakens the conclusions regarding novel or other risk
factors.
2. The manuscript utilizes a classification for Portal Vein Thrombosis (PVT) (e.g., partial/
complete, acute/chronic, extent). However, it does not explicitly state which specific
classification criteria or definitions were applied at the study center. To ensure clarity and
reproducibility, please explicitly reference the specific PVT classification standard used in your
center (e.g., Yerdel classification, European Association for the Study of the Liver (EASL)
guidelines definitions, American Association for the Study of Liver Diseases (AASLD) practice
guidance definitions, or an internally validated protocol).
3. On Page 5, Lines 96-97, the text states: " This study implemented three distinct patient
groupings to evaluate the relationships between clinical variables and outcomes" However, the
subsequent description (Lines 97-100) details only two distinct grouping methods.
Provide the missing description for the third grouping method  and ensure the results analysis
consistently reflects all three groupings mentioned.
assistant