Validation and Comparison of Non-Invasive Tests for the Exclusion of High-Risk Varices in Compensated Advanced Chronic Liver Disease

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This retrospective study aimed to validate and compare various non-invasive tests (NITs) as a potential alternative to screening oesophagogastroduodenoscopy (OGD) for ruling out high-risk varices (HRV) in patients with compensated advanced chronic liver disease (cACLD) in an Australian cohort. They concluded that the Baveno VI criteria can be applied in an Australian, mixed aetiology cohort to avoid unnecessary screening OGD. The contents of this manuscript could provide clinically applicable data.

Minor comment:

The sentences from line 260-269 duplicated all contents of Table 5. Authors should revise these sentences as more concise description.

Author Response

Thank you very much for taking the time to review this manuscript and for this comment. We have revised these sentences to better describe the results. The changes can be found from line 261-269.

Reviewer 2 Report

Comments and Suggestions for Authors

I have carefully studied the manuscript entitled "Validation and comparison of non-invasive tests for the exclusion of high-risk varices in compensated advanced chronic liver disease" by Kurup R et al.

The manuscript aims to compare non-invasive tests in ruling out high-risk varices in patients with compensated advanced chronic liver disease without performing oesophagogastroduodenoscopy by retrospectively evaluating nationwide data in Australia. As a conclusion, the authors validated the BAVENO VI criteria in contrast with several other non-invasive approaches, including FIB-4, APRI, MELD, MELD-Na, FIPS, and EVendo. 

Despite that the manuscript is well written, the authors are welcome to address some issues regarding methodology and statistical analysis as follows.

Major issues

1. Line 87: The authors state that "Diagnosis of cACLD was defined as asymptomatic patients with chronic liver disease and LSM by transient elastography (TE) of ≥10 kPa". Since there is still much debate on the relevant optimal LSM cut-off, the authors are kindly requested to provide a reference.

2.  Line 179 (Table 1): The median LSM value of "all patients" (20.25 kPa) is lower than both medians derived from the two comprising groups ("No HRV" group: 21.95 kPa, "HRV" group: 29.8 kPa).

Minor issue

1. Line 179 (Table 1): The authors are kindly requested to specify the test used to compare each continuous variable between the "No HRV" group and the "HRV" group (Student's t-test vs. Mann-Whitney U test). 

Author Response

Thank you very much for taking the time to review this manuscript and for your comments. Please find our responses below.

Comment 1:

Line 87: The authors state that "Diagnosis of cACLD was defined as asymptomatic patients with chronic liver disease and LSM by transient elastography (TE) of ≥10 kPa". Since there is still much debate on the relevant optimal LSM cut-off, the authors are kindly requested to provide a reference.

Response 1:

Thank you for pointing this out. We agree with this and have listed a reference for this statement which can be found in line 95.

 

Comment 2:

Line 179 (Table 1): The median LSM value of "all patients" (20.25 kPa) is lower than both medians derived from the two comprising groups ("No HRV" group: 21.95 kPa, "HRV" group: 29.8 kPa).

Response 2:

Thank you for noting this. We have corrected this error after rechecking our analysis and the change can be found in line 188.

 

Comment 3:

Line 179 (Table 1): The authors are kindly requested to specify the test used to compare each continuous variable between the "No HRV" group and the "HRV" group (Student's t-test vs. Mann-Whitney U test). 

Response 3:

Thank you for pointing this out. We agree with this and have specified the type of test for the continuous variables and these changes can be found in line 161-165.

Reviewer 3 Report

Comments and Suggestions for Authors

The introduction provides a concise overview of compensated advanced chronic liver disease (cACLD) and the importance of detecting high-risk varices (HRV) to prevent variceal bleeding. Clear statistics and references are provided to support the significance of the issue. The study methodology is well-described, providing details on the study population, data collection methods, and statistical analyses used. Inclusion and exclusion criteria are clearly defined, ensuring the homogeneity of the study population. The results section presents the baseline characteristics of the study cohort effectively, using tables for clear presentation of demographic and clinical data. The findings are discussed in relation to the study objectives, focusing on the performance of non-invasive tests (NITs) in predicting HRV. Subgroup analysis results provide additional insights into the efficacy of NITs across different etiologies of cACLD. The discussion thoroughly interprets the study findings, comparing them with existing literature and discussing implications. Strengths and limitations of the study are appropriately acknowledged, enhancing the credibility of the findings.

Recommendations for future research and clinical practice are provided, addressing the need for further validation of NITs and considering the impact of findings on patient care.

Overall impression

The article is well-structured, with a clear flow from introduction to discussion. Data presentation is comprehensive and aids in understanding the study findings. The discussion is insightful, providing valuable context and implications of the study results. The article adheres to scientific standards and contributes to the literature on non-invasive assessment of HRV in patients with cACLD. Overall, the article effectively addresses its objectives and makes a valuable contribution to the field of hepatology.

Author Response

Thank you very much for taking the time to review our manuscript and for your kind comments.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors I have studied the revised version of the manuscript entitled "Validation and comparison of non-invasive tests for the exclusion of high-risk varices in compensated advanced chronic liver disease" by Kurup R. et al. The auhtors have successfully responded to all queries raised throughout the reviewing process. The quality of the manuscript has been ameliorated. There are no additional issues raised.