Grading of Fatty Liver Based on Computed Tomography Hounsfield Unit Values versus Ultrasonography Grading

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors present an interesting, though not very novel study, trying to correlate the findings of C/T and U/S in terms of liver steatosis measurement, proving that C/T is a relaiable and objective method of measuring liver steatosis. The manuscript is well written and the results are clearly presented, however a few changes must be made.

1. In the second paragraph of page 2 the authors state 3 risk factors for MASLD. This is wrong, since steatosis, steatohepatitis and fibrosis represent stages rather than risk factors for MASLD

2. In the same page, in the last paragraph of introduction section, a few sentences regarding serum non-invasive biomarkers should be added (ref: doi:10.2174/1570162X17666190809153245; doi:10.1007/s13679-024-00574-z; doi:10.1097/HEP.0000000000000842)

3. The authors should try to find a cut-off with the highest possible sensitivity separating mild/no and significant steatosis (S0-S1 vs S2-S3)  

4. A paragraph summarizing what new this manuscript brings to the literature should be added 

5. In limitations section, the fact that the 'gold standard' of the study is the measurement of steatosis in ultrasound, which is a subjective measurement should be added.

Comments on the Quality of English Language

Minor english editing required

Author Response

Comment-1. In the second paragraph of page-2 the authors state 3 risk factors for MASLD. This is wrong, since steatosis, steatohepatitis, and fibrosis represent stages rather than risk factors for MASLD.

Reply, this paragraph was corrected. “Risk factors” was changed to “risk phases”

Comment-2, In the same page, in the last paragraph of introduction section, a few sentences regarding serum non-invasive biomarkers should be added. 

Reply, this study concentrated on medical imaging methods of grading of MASLD. Really, we concentrated only on CT and Ultrasonography, and we omitted other significant imaging methods such as MRI, and elastography. Although laboratory markers can help in diagnosis of fatty liver, they cannot help in fatty liver grading, so that, we concentrated on our aim.

Comment-3, The authors should try to add a cut-off with the highest possible sensitivity separating the mild/no and significant steatosis (S0-S1 vs S2-S3).

Reply, This was already written in the results and discussion section. We add this sentence in conclusion “Liver density of 48.9 HU was the cut-off separating grade 0/grade 1 and the significant high grades of steatosis”.

Comment-4, A paragraph summarizing what new this manuscript brings to the literature should be added.

Reply, we added this paragraph at the end of the introduction section “This study will add a quantitative and easily calculable method for grading of fatty liver away from the subjective ultrasonography grading which is an operator-dependent.”

Comment-5, in the limitation section, the fact that the “gold standard” of the study is the measurement of steatosis in ultrasound, which is a subjective measurement should be added. 

Reply, we added the following paragraph to the limitation “Grading of liver steatosis was done using ultrasonography, which is a good method for assessment of liver steatosis, however, it is subjective and non-digital. We have overcome this problem by independently assessing each patient by two experienced radiologists and selected the patients when the two radiologists agreed on the grading”

Comment-6, 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Comments to the Authors of manuscript entitled “Grading of fatty liver based on computed tomography Hounsfield unit values versus ultrasonography grading”

 

1. Page 1 “FLD” - abbr. is used for the first time and should be explained

2. P 1-  “and related disorders [3]”- an example needed

3. The hypothesis is presented clearly, but the goal of the study not.

4. what were inclusion criteria relating to that diagnosis with fatty liver by ultrasonography?

5. The study did not include histological confirmation of liver fat, which is the gold standard for diagnosing and grading MASLD. Incorporating histological validation would strengthen the study’s conclusions and provide a more accurate assessment of liver fat content. It is highlighted as a limitation.

6. The significant overlap in HU values between different MASLD grades, particularly between grade 0 (normal liver) and grade 1, as well as between grades 1 and 2, raises concerns about the accuracy and reliability of using NCCT for MASLD grading. This overlap suggests that NCCT may not be sufficiently precise to distinguish between these grades, potentially leading to misclassification.

7. NCCT should be used as a primary diagnostic tool or if it should be supplemented with other imaging modalities or diagnostic methods?

8. The potential clinical impact of the new numeric, calculable, and objective method for grading MASLD should be explored in greater depth. This includes discussing how this method could improve patient outcomes, streamline diagnosis, and reduce subjective variation in MASLD grading.

9. The study should provide a more comprehensive comparison with other similar studies, particularly those that have used different methods or imaging techniques for MASLD grading.

10. Addressing these points in a revised study would be essential for producing robust and clinically applicable findings.

11. different fonts in the manuscript, and lack the numbered lines.

Author Response

Comment-1, Page 1, FLD -abbr. is used for the first time and should be explained.

Reply, Explanation of the abbreviation was done. “FLD” to “Liver steatosis”

Comment-2, P 1.  –“and related disorders [3}”-an example needed. 

Reply, this was done. “ ….. such as hyperlipidemia.”

Comment-3, The hypothesis is presented clearly, but the goal of the study not.

Reply, this was clarified as the following: “… and develop a new numerical calculable method for grading …”

Comment-4, What were inclusion criteria relating to that diagnosis with fatty liver by ultrasonography? 

Reply, these have a paragraph in the introduction section: “Ultrasonography is used to diagnose and grade MASLD by scoring liver brightness, the blurring of vessels, and the diaphragm [10]. Ultrasonography can be used for grading MASLD using a four-point scale as follows: normal liver echogenicity (grade 0), diffusely increased liver echogenicity and appreciable periportal and diaphragm echogenicity (grade 1), diffusely increased liver echogenicity obscuring periportal and appreciable diaphragm echogenicity (grade 2), and diffusely increased liver echogenicity obscuring periportal and diaphragm echogenicity (grade 3) [11].”

Comment-5, The study did not have histological confirmation of liver fat, which is the gold standard for diagnosis and grading MASLD. Incorporating histological validation would strengthen the study’s conclusion and provide a more accurate assessment of liver fat content. It is highlighted as a limitation.

Reply, unfortunately, a histological confirmation of the liver fat was not performed. We solved this limitation as the following: “Grading of liver steatosis was done using ultrasonography, which is a good method for assessment of liver steatosis, however, it is subjective and non-digital. We have overcome this problem by independently assessing each patient by two experienced radiologists and selected the patients when the two radiologists agreed on the grading. We have added guidelines for related future research as the following: “Future direction: A prospective study with large sample size and more than two observers to grade fatty liver using ultrasonography and more than one observer to read the liver density on NCCT images for each patient with available histological confirmation of the liver fat is recommended to create more accurate scale for grading of MASLD.”

Comment-6, the significant overlap in HU values between different MASLD grades, particularly between grade 0 (normal liver) and grade 1, as well as between grades 1 and 2, raises concerns about the accuracy and liability of using NCCT for MASLD grading. This overlap suggests that NCCT may not be sufficiently precise to distinguish between these grades, potentially leading to misclassification.

Reply, although, the significant overlap in HU values between different MASLD grades, NCCT offers a numerical calculable non-invasive method for grading available for radiologists, technologists and even physicians with more accuracy than ultrasonography which has significant overlapping in grading. 

Comment-7, NCCT should be used as a primary diagnostic tool or if it should be supplemented with other imaging modalities or diagnostic methods?

Reply, NCCT offers a numerical method for grading MASLD. Ultrasonography is the provisional method for MASLD diagnosis. We modified conclusion as the following:

“After ultrasonography diagnosis of MASLD, NCCT offers an objective, numerical, calculable and non-invasive method for MASLD grading available for radiologists, technologists and even physicians.”

Comment-8, the potential clinical impact of new numeric, calculable and objective method for grading MASLD should be explored in greater depth. This includes discussing how this method could improve patients’ outcomes, streamline diagnosis, and reduce subjective variation in MASLD grading.

Reply, calculable numerical grading will be easily available for any healthcare provider including radiology technologists and physicians away from the impact of experience as in ultrasonography. We suppose that implantation of this study will provide more accurate method for MASLD grading than ultrasonography.

Comment-9, the study should provide a more comprehensive comparison with other similar studies, particularly those that used different methods or imaging techniques for MASLD grading.

Reply, this study provided comparison of HU values in different grades of MASLD such as reference-20 which was published in “Radiology” journal. Unfortunately, we did not find a detailed previous study using of NCCT for MASLD grading. We add future direction as the following:

“Future direction: A prospective study with large sample size and more than two observers to grade fatty liver using ultrasonography and more than one observer to read the liver density on NCCT images for each patient with available histological confirmation of the liver fat is recommended to create more accurate scale for grading of MASLD.”

Comment-10, Addressing these points in a revised study would be essential for producing robust and clinically applicable findings.

Reply, we would like to thank you for your great effect in revising this manuscript and for your highly valuable points to improve our work. We did all of the possible revisions and corrections.

Comment-11, Different fonts in the manuscript and lack of numbered lines.

Reply, the language editing, and coordination will be the final step.

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

In this manuscript, the authors assess the feasibility of grading Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) using Non-Contrast Computed Tomography (NCCT) with Hounsfield Units (HU). The topic is interesting and worth investigating. The obtained results show the effectiveness of the proposed method. The manuscript is well written and well organized.

 

My remarks are as follows:

In the abstract and introduction sections, the novelty and the authors' contributions should be better clarified.

In the final section, future research directions should be addressed.

 

Technical remarks:

The font size of measurements in the fourth column of Figure 3 should be enlarged.

The font size of subsection names after the Conclusion section should be decreased. The same applies to the reference list formatting.

Author Response

Comment-1, in the abstract and introduction sections, the novelty and the authors, contribution should be better clarified.

Reply, the author’s contribution was addressed as the following: “This study will add a quantitative and easily calculable method for grading of fatty liver away from the subjective ultrasonography grading which is an operator-dependent.”

Comment-2, in the final section, future research directions should be addressed. 

Reply, future research direction was addressed as the following:

“Future direction: A prospective study with large sample size and more than two observers to grade fatty liver using ultrasonography and more than one observer to read the liver density on NCCT images for each patient with available histological confirmation of the liver fat is recommended to create more accurate scale for grading of MASLD.”

Comment-3, the font size of measurements in the fourth column of figure-3 should be enlarged.

Reply, in figure 4, the font size of measurements on CT images cannot be enlarged because it is written on images, however, the measurements are clarified in the legend of the figure.

Comment-4, the font size of subsections names after the conclusion section should be decreased. The same applied to the reference list formatting.

Reply, the font size was corrected in the following:

-Authors contribution

-Funding

-Data availability statement

-Competing interests

-References

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have made crucial changes to their manuscript which I believe is now eligible for publication

Comments on the Quality of English Language

Minor editing needed