Title: Strain Elastography for Detecting Advanced Fontan-Associated Liver Disease: A
Retrospective Study
Version: 1 Date: 21 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The sample size of 46 patients is relatively small, which could limit the generalizability of the
findings. A larger cohort would strengthen the conclusions and allow for more robust subgroup
analyses. The limited sample size may also impact the statistical power of the study, particularly
when examining rare outcomes such as hepatocellular carcinoma or liver transplantation.
-Although the study provides a snapshot of FALD patients' liver status, the cross-sectional design
does not capture changes over time. Longitudinal follow-up would be ideal for assessing the
progression of liver disease and the effectiveness of non-invasive tests in monitoring disease
progression over the long term.
-While the study rules out other liver diseases, it does not fully address potential confounding
factors such as the impact of anticoagulant therapy or comorbidities on liver function. Although
the study focuses on FALD, the influence of other conditions could still play a role in liver
fibrosis progression, and the lack of detailed data on these confounders could be a limitation.
-The study’s findings are based on patients from a single academic center, which may limit the
external validity of the results. Variations in practice across different healthcare settings and
patient populations could affect the applicability of the results to other hospitals or regions.
-While combining SWE and SE is innovative, relying on single-point elastography
measurements might not account for intra-patient liver heterogeneity. Multiple measurements
across different regions of the liver could provide a more comprehensive assessment.
-The study mentions that MRE and TE have been used in previous studies for liver stiffness
measurement in FALD patients, but it does not explore these techniques in detail. A comparison
of SE with MRE and TE would be valuable to further substantiate the claim that SE is less
affected by hepatic congestion and inflammation.
-The complexity of combining SWE and SE, along with the calculation of the liver fibrosis
index (LFI), may limit the widespread adoption of this method in routine clinical practice. The
study does not address the potential challenges in interpreting these elastography measures,
particularly in a clinical setting with limited access to advanced imaging technologies.
-The discussion mentions that the study did not investigate the correlation between histological
findings (from liver biopsies) and the NITs. While the study appropriately acknowledges this
limitation, a deeper explanation of the potential implications of this gap would have been
beneficial. Without histological confirmation of the fibrosis stages, the study's findings on LFI
might not be as definitive as they would be with biopsy-based validation.
-The discussion notes that the median time between cardiac catheterization and abdominal
ultrasound (US) was 2.11 years, which may influence the reliability of the results. The potential
confounding effect of this time gap could have been explored further. Discussing the possibility
that the progression of liver disease could have occurred between measurements and how this
might impact the study's results would strengthen this section.
-The discussion mainly focuses on platelet counts, non-invasive scores, and LFI derived from
SE as predictors of NAFLD. However, other factors, such as the impact of treatment regimens
(e.g., anticoagulants, diuretics), liver inflammation, and hepatic congestion, could have been
explored in greater detail. These factors could contribute to the progression of FALD and should
be considered when interpreting the results.
-Although the study is positioned as a first of its kind in assessing SE-derived LFI in FALD
patients, the discussion could have expanded on the need for validation in different patient
populations, especially those with varying underlying heart conditions or comorbidities that may
affect liver health.
Title: Strain Elastography for Detecting Advanced Fontan-Associated Liver Disease: A
Retrospective Study
Version: 1 Date: 21 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The sample size of 46 patients is relatively small, which could limit the generalizability of the
findings. A larger cohort would strengthen the conclusions and allow for more robust subgroup
analyses. The limited sample size may also impact the statistical power of the study, particularly
when examining rare outcomes such as hepatocellular carcinoma or liver transplantation.
-Although the study provides a snapshot of FALD patients' liver status, the cross-sectional design
does not capture changes over time. Longitudinal follow-up would be ideal for assessing the
progression of liver disease and the effectiveness of non-invasive tests in monitoring disease
progression over the long term.
-While the study rules out other liver diseases, it does not fully address potential confounding
factors such as the impact of anticoagulant therapy or comorbidities on liver function. Although
the study focuses on FALD, the influence of other conditions could still play a role in liver
fibrosis progression, and the lack of detailed data on these confounders could be a limitation.
-The study’s findings are based on patients from a single academic center, which may limit the
external validity of the results. Variations in practice across different healthcare settings and
patient populations could affect the applicability of the results to other hospitals or regions.
-While combining SWE and SE is innovative, relying on single-point elastography
measurements might not account for intra-patient liver heterogeneity. Multiple measurements
across different regions of the liver could provide a more comprehensive assessment.
-The study mentions that MRE and TE have been used in previous studies for liver stiffness
measurement in FALD patients, but it does not explore these techniques in detail. A comparison
of SE with MRE and TE would be valuable to further substantiate the claim that SE is less
affected by hepatic congestion and inflammation.
-The complexity of combining SWE and SE, along with the calculation of the liver fibrosis
index (LFI), may limit the widespread adoption of this method in routine clinical practice. The
study does not address the potential challenges in interpreting these elastography measures,
particularly in a clinical setting with limited access to advanced imaging technologies.
-The discussion mentions that the study did not investigate the correlation between histological
findings (from liver biopsies) and the NITs. While the study appropriately acknowledges this
limitation, a deeper explanation of the potential implications of this gap would have been
beneficial. Without histological confirmation of the fibrosis stages, the study's findings on LFI
might not be as definitive as they would be with biopsy-based validation.
-The discussion notes that the median time between cardiac catheterization and abdominal
ultrasound (US) was 2.11 years, which may influence the reliability of the results. The potential
confounding effect of this time gap could have been explored further. Discussing the possibility
that the progression of liver disease could have occurred between measurements and how this
might impact the study's results would strengthen this section.
-The discussion mainly focuses on platelet counts, non-invasive scores, and LFI derived from
SE as predictors of NAFLD. However, other factors, such as the impact of treatment regimens
(e.g., anticoagulants, diuretics), liver inflammation, and hepatic congestion, could have been
explored in greater detail. These factors could contribute to the progression of FALD and should
be considered when interpreting the results.
-Although the study is positioned as a first of its kind in assessing SE-derived LFI in FALD
patients, the discussion could have expanded on the need for validation in different patient
populations, especially those with varying underlying heart conditions or comorbidities that may
affect liver health.
Please review this paper.
user
Title: Strain Elastography for Detecting Advanced Fontan-Associated Liver Disease: A
Retrospective Study
Version: 1 Date: 21 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The sample size of 46 patients is relatively small, which could limit the generalizability of the
findings. A larger cohort would strengthen the conclusions and allow for more robust subgroup
analyses. The limited sample size may also impact the statistical power of the study, particularly
when examining rare outcomes such as hepatocellular carcinoma or liver transplantation.
-Although the study provides a snapshot of FALD patients' liver status, the cross-sectional design
does not capture changes over time. Longitudinal follow-up would be ideal for assessing the
progression of liver disease and the effectiveness of non-invasive tests in monitoring disease
progression over the long term.
-While the study rules out other liver diseases, it does not fully address potential confounding
factors such as the impact of anticoagulant therapy or comorbidities on liver function. Although
the study focuses on FALD, the influence of other conditions could still play a role in liver
fibrosis progression, and the lack of detailed data on these confounders could be a limitation.
-The study’s findings are based on patients from a single academic center, which may limit the
external validity of the results. Variations in practice across different healthcare settings and
patient populations could affect the applicability of the results to other hospitals or regions.
-While combining SWE and SE is innovative, relying on single-point elastography
measurements might not account for intra-patient liver heterogeneity. Multiple measurements
across different regions of the liver could provide a more comprehensive assessment.
-The study mentions that MRE and TE have been used in previous studies for liver stiffness
measurement in FALD patients, but it does not explore these techniques in detail. A comparison
of SE with MRE and TE would be valuable to further substantiate the claim that SE is less
affected by hepatic congestion and inflammation.
-The complexity of combining SWE and SE, along with the calculation of the liver fibrosis
index (LFI), may limit the widespread adoption of this method in routine clinical practice. The
study does not address the potential challenges in interpreting these elastography measures,
particularly in a clinical setting with limited access to advanced imaging technologies.
-The discussion mentions that the study did not investigate the correlation between histological
findings (from liver biopsies) and the NITs. While the study appropriately acknowledges this
limitation, a deeper explanation of the potential implications of this gap would have been
beneficial. Without histological confirmation of the fibrosis stages, the study's findings on LFI
might not be as definitive as they would be with biopsy-based validation.
-The discussion notes that the median time between cardiac catheterization and abdominal
ultrasound (US) was 2.11 years, which may influence the reliability of the results. The potential
confounding effect of this time gap could have been explored further. Discussing the possibility
that the progression of liver disease could have occurred between measurements and how this
might impact the study's results would strengthen this section.
-The discussion mainly focuses on platelet counts, non-invasive scores, and LFI derived from
SE as predictors of NAFLD. However, other factors, such as the impact of treatment regimens
(e.g., anticoagulants, diuretics), liver inflammation, and hepatic congestion, could have been
explored in greater detail. These factors could contribute to the progression of FALD and should
be considered when interpreting the results.
-Although the study is positioned as a first of its kind in assessing SE-derived LFI in FALD
patients, the discussion could have expanded on the need for validation in different patient
populations, especially those with varying underlying heart conditions or comorbidities that may
affect liver health.
assistant