Title: Assessing the consistency of FIB-4, APRI, and GPR in evaluating significant liver fibrosis
and cirrhosis in COVID-19 patients with concurrent liver diseases
Version: 0 Date: 16 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The introduction mentions both direct and indirect mechanisms of liver injury caused by
COVID-19 but lacks detailed explanations or references on how each mechanism works. For
instance, it would be beneficial to briefly explain the pathophysiology behind liver ischemia,
hypoxia, and drug-induced liver injury in the context of COVID-19 to provide a fuller picture
for readers unfamiliar with these processes.
-The studies referenced in the introduction are pivotal in establishing the background, but the
citation formatting can be improved. For example, references like [2] and [4] are provided
without full citation details, making it difficult for readers to verify or explore the sources. Ensure
proper reference formatting and consistency.
-While the introduction mentions limited research on non-invasive assessments for liver fibrosis
in COVID-19 patients, it would benefit from a brief mention of any prior studies that have
assessed liver fibrosis in COVID-19 patients or similar populations (even if they are limited).
This helps contextualize the current study within the existing literature, demonstrating the gap
the research is attempting to fill.
-While the study focuses on FIB-4, APRI, and GPR, there is little justification for why these
specific indices were chosen over others, especially since there are several other non-invasive
tests available. A brief discussion about their relative advantages and disadvantages or their
previous usage in similar patient populations would strengthen the rationale for their selection.
-In the Materials and Methods section, patients are divided into three groups based on liver
disease (NAFLD, CHB, and both). It would be helpful to elaborate on how potential confounders
(such as age, comorbidities, or disease severity) were addressed in the analysis or how they might
affect the study's outcomes. Also, how the co-existence of NAFLD and CHB may complicate
the interpretation of non-invasive liver fibrosis markers could be discussed in more detail.
-The study cites several guidelines and scoring systems, including the METAVIR system and
various liver disease guidelines. However, these could be briefly explained in layman's terms (or
references provided) for readers unfamiliar with them. For example, how are significant fibrosis
and cirrhosis diagnosed in COVID-19 patients, and how does the METAVIR score play a role
in defining these categories?
-While the use of Kappa analysis is mentioned, further explanation of the significance of Kappa
values in the context of this study would be helpful. The discussion could benefit from a brief
mention of what constitutes "strong" or "moderate" consistency based on Kappa's scale (e.g.,
0.81-1.0 is almost perfect, 0.61-0.80 substantial, etc.). This would make the findings more
accessible to readers who are less familiar with statistical concepts.
-The section on the clinical significance of the findings (e.g., the linear relationship between
liver fibrosis and the incidence of severe COVID-19) could be expanded. While it’s mentioned
that increased liver fibrosis correlates with more severe COVID-19, a deeper exploration of why
this might be the case would add value. This could include discussing potential mechanisms,
such as immune dysregulation or the impact of advanced liver disease on respiratory function.
-Additionally, more explicit recommendations for clinical practice, such as whether certain
combinations of FIB-4, APRI, and GPR should be preferred based on patient characteristics
(e.g., NAFLD vs. CHB), would enhance the practical utility of the findings.
-Some statements could benefit from further clarification or a more nuanced discussion. For
example, it would be helpful to elaborate on the moderate consistency between FIB-4 and
APRI when assessing non-significant liver fibrosis and cirrhosis. While it is mentioned that this
consistency is moderate, providing more context about why this might be the case would be
beneficial.
Title: Assessing the consistency of FIB-4, APRI, and GPR in evaluating significant liver fibrosis
and cirrhosis in COVID-19 patients with concurrent liver diseases
Version: 0 Date: 16 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The introduction mentions both direct and indirect mechanisms of liver injury caused by
COVID-19 but lacks detailed explanations or references on how each mechanism works. For
instance, it would be beneficial to briefly explain the pathophysiology behind liver ischemia,
hypoxia, and drug-induced liver injury in the context of COVID-19 to provide a fuller picture
for readers unfamiliar with these processes.
-The studies referenced in the introduction are pivotal in establishing the background, but the
citation formatting can be improved. For example, references like [2] and [4] are provided
without full citation details, making it difficult for readers to verify or explore the sources. Ensure
proper reference formatting and consistency.
-While the introduction mentions limited research on non-invasive assessments for liver fibrosis
in COVID-19 patients, it would benefit from a brief mention of any prior studies that have
assessed liver fibrosis in COVID-19 patients or similar populations (even if they are limited).
This helps contextualize the current study within the existing literature, demonstrating the gap
the research is attempting to fill.
-While the study focuses on FIB-4, APRI, and GPR, there is little justification for why these
specific indices were chosen over others, especially since there are several other non-invasive
tests available. A brief discussion about their relative advantages and disadvantages or their
previous usage in similar patient populations would strengthen the rationale for their selection.
-In the Materials and Methods section, patients are divided into three groups based on liver
disease (NAFLD, CHB, and both). It would be helpful to elaborate on how potential confounders
(such as age, comorbidities, or disease severity) were addressed in the analysis or how they might
affect the study's outcomes. Also, how the co-existence of NAFLD and CHB may complicate
the interpretation of non-invasive liver fibrosis markers could be discussed in more detail.
-The study cites several guidelines and scoring systems, including the METAVIR system and
various liver disease guidelines. However, these could be briefly explained in layman's terms (or
references provided) for readers unfamiliar with them. For example, how are significant fibrosis
and cirrhosis diagnosed in COVID-19 patients, and how does the METAVIR score play a role
in defining these categories?
-While the use of Kappa analysis is mentioned, further explanation of the significance of Kappa
values in the context of this study would be helpful. The discussion could benefit from a brief
mention of what constitutes "strong" or "moderate" consistency based on Kappa's scale (e.g.,
0.81-1.0 is almost perfect, 0.61-0.80 substantial, etc.). This would make the findings more
accessible to readers who are less familiar with statistical concepts.
-The section on the clinical significance of the findings (e.g., the linear relationship between
liver fibrosis and the incidence of severe COVID-19) could be expanded. While it’s mentioned
that increased liver fibrosis correlates with more severe COVID-19, a deeper exploration of why
this might be the case would add value. This could include discussing potential mechanisms,
such as immune dysregulation or the impact of advanced liver disease on respiratory function.
-Additionally, more explicit recommendations for clinical practice, such as whether certain
combinations of FIB-4, APRI, and GPR should be preferred based on patient characteristics
(e.g., NAFLD vs. CHB), would enhance the practical utility of the findings.
-Some statements could benefit from further clarification or a more nuanced discussion. For
example, it would be helpful to elaborate on the moderate consistency between FIB-4 and
APRI when assessing non-significant liver fibrosis and cirrhosis. While it is mentioned that this
consistency is moderate, providing more context about why this might be the case would be
beneficial.
Please review this paper.
user
Title: Assessing the consistency of FIB-4, APRI, and GPR in evaluating significant liver fibrosis
and cirrhosis in COVID-19 patients with concurrent liver diseases
Version: 0 Date: 16 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The introduction mentions both direct and indirect mechanisms of liver injury caused by
COVID-19 but lacks detailed explanations or references on how each mechanism works. For
instance, it would be beneficial to briefly explain the pathophysiology behind liver ischemia,
hypoxia, and drug-induced liver injury in the context of COVID-19 to provide a fuller picture
for readers unfamiliar with these processes.
-The studies referenced in the introduction are pivotal in establishing the background, but the
citation formatting can be improved. For example, references like [2] and [4] are provided
without full citation details, making it difficult for readers to verify or explore the sources. Ensure
proper reference formatting and consistency.
-While the introduction mentions limited research on non-invasive assessments for liver fibrosis
in COVID-19 patients, it would benefit from a brief mention of any prior studies that have
assessed liver fibrosis in COVID-19 patients or similar populations (even if they are limited).
This helps contextualize the current study within the existing literature, demonstrating the gap
the research is attempting to fill.
-While the study focuses on FIB-4, APRI, and GPR, there is little justification for why these
specific indices were chosen over others, especially since there are several other non-invasive
tests available. A brief discussion about their relative advantages and disadvantages or their
previous usage in similar patient populations would strengthen the rationale for their selection.
-In the Materials and Methods section, patients are divided into three groups based on liver
disease (NAFLD, CHB, and both). It would be helpful to elaborate on how potential confounders
(such as age, comorbidities, or disease severity) were addressed in the analysis or how they might
affect the study's outcomes. Also, how the co-existence of NAFLD and CHB may complicate
the interpretation of non-invasive liver fibrosis markers could be discussed in more detail.
-The study cites several guidelines and scoring systems, including the METAVIR system and
various liver disease guidelines. However, these could be briefly explained in layman's terms (or
references provided) for readers unfamiliar with them. For example, how are significant fibrosis
and cirrhosis diagnosed in COVID-19 patients, and how does the METAVIR score play a role
in defining these categories?
-While the use of Kappa analysis is mentioned, further explanation of the significance of Kappa
values in the context of this study would be helpful. The discussion could benefit from a brief
mention of what constitutes "strong" or "moderate" consistency based on Kappa's scale (e.g.,
0.81-1.0 is almost perfect, 0.61-0.80 substantial, etc.). This would make the findings more
accessible to readers who are less familiar with statistical concepts.
-The section on the clinical significance of the findings (e.g., the linear relationship between
liver fibrosis and the incidence of severe COVID-19) could be expanded. While it’s mentioned
that increased liver fibrosis correlates with more severe COVID-19, a deeper exploration of why
this might be the case would add value. This could include discussing potential mechanisms,
such as immune dysregulation or the impact of advanced liver disease on respiratory function.
-Additionally, more explicit recommendations for clinical practice, such as whether certain
combinations of FIB-4, APRI, and GPR should be preferred based on patient characteristics
(e.g., NAFLD vs. CHB), would enhance the practical utility of the findings.
-Some statements could benefit from further clarification or a more nuanced discussion. For
example, it would be helpful to elaborate on the moderate consistency between FIB-4 and
APRI when assessing non-significant liver fibrosis and cirrhosis. While it is mentioned that this
consistency is moderate, providing more context about why this might be the case would be
beneficial.
assistant