Title: Differential effects of systemic immune inflammation indices on hepatic steatosis and
hepatic fibrosis: evidence from NHANES 1999-2018
Version: 0 Date: 18 Nov 2024
Reviewer's report:
This cross-sectional study by Shuyin et al. analyzed data from 21,833 NHANES participants to
investigate the relationship between the Systemic Immune Inflammation Index (SII) and hepatic
fibrosis/steatosis. Using multiple biomarkers, the research revealed a negative association
between SII and hepatic fibrosis, while finding a positive association with hepatic steatosis. The
study utilized complex statistical methods including Pearson's correlation, generalized linear
models, and restricted cubic splines. The findings suggest SII could be a cost-effective, easily
obtainable marker for assessing liver health. The results highlight the complex interplay between
systemic inflammation and liver pathology. Despite being well written and intriguing study,
there are some comments that needs to be addressed:
1.  The manuscript provides valuable insights into the relationship between the Systemic Immune
Inflammation Index (SII) and hepatic steatosis and fibrosis. However, the study misses an
important opportunity to compare SII with other well-established inflammation markers such as
CRP, ESR and WBC. These biomarkers are frequently used in clinical practice to assess systemic
inflammation. It would be important to analyze whether these traditional markers demonstrate
similar associations with hepatic steatosis and fibrosis as observed with SII. This comparison
would strengthen the argument for using SII as a preferred marker.
2. The study relies on non-invasive biomarkers. While these indices are valuable, the lack of
data from more direct diagnostic tools such as abdominal ultrasound for steatosis evaluation,
FibroScan for fibrosis evaluation, or liver biopsy for both limits the robustness of the findings.
Including data from these modalities would provide a more comprehensive validation of the
observed associations and offer insights into the diagnostic accuracy of SII compared to
established imaging and histological methods.
3. While the manuscript provides some evidence on the associations between SII and hepatic
steatosis and fibrosis, it lacks a comprehensive discussion on how these findings could be
incorporated into clinical practice or influence screening strategies. The current conclusions
highlight SII's potential utility, but practical guidance for clinicians is missing.
4. The manuscript does not provide clarity on whether the patients in the study cohort have pre-
existing liver disease, nor does it specify the types of liver disease present . In addition, we don't
know how many of the patients in the cohort have other inflammatory diseases  such as RA
or SLE, for example.  This is a significant limitation, as the behavior of the Systemic Immune
Inflammation Index (SII) may vary across different liver disease/systemic disease etiologies.
5. The manuscript does not address whether patients with cirrhosis are included in the study
cohort. This omission is important, as the Systemic Immune Inflammation Index (SII) may
behave differently in cirrhotic patients compared to those with non-cirrhotic liver disease.
Title: Differential effects of systemic immune inflammation indices on hepatic steatosis and
hepatic fibrosis: evidence from NHANES 1999-2018
Version: 0 Date: 18 Nov 2024
Reviewer's report:
This cross-sectional study by Shuyin et al. analyzed data from 21,833 NHANES participants to
investigate the relationship between the Systemic Immune Inflammation Index (SII) and hepatic
fibrosis/steatosis. Using multiple biomarkers, the research revealed a negative association
between SII and hepatic fibrosis, while finding a positive association with hepatic steatosis. The
study utilized complex statistical methods including Pearson's correlation, generalized linear
models, and restricted cubic splines. The findings suggest SII could be a cost-effective, easily
obtainable marker for assessing liver health. The results highlight the complex interplay between
systemic inflammation and liver pathology. Despite being well written and intriguing study,
there are some comments that needs to be addressed:
1.  The manuscript provides valuable insights into the relationship between the Systemic Immune
Inflammation Index (SII) and hepatic steatosis and fibrosis. However, the study misses an
important opportunity to compare SII with other well-established inflammation markers such as
CRP, ESR and WBC. These biomarkers are frequently used in clinical practice to assess systemic
inflammation. It would be important to analyze whether these traditional markers demonstrate
similar associations with hepatic steatosis and fibrosis as observed with SII. This comparison
would strengthen the argument for using SII as a preferred marker.
2. The study relies on non-invasive biomarkers. While these indices are valuable, the lack of
data from more direct diagnostic tools such as abdominal ultrasound for steatosis evaluation,
FibroScan for fibrosis evaluation, or liver biopsy for both limits the robustness of the findings.
Including data from these modalities would provide a more comprehensive validation of the
observed associations and offer insights into the diagnostic accuracy of SII compared to
established imaging and histological methods.
3. While the manuscript provides some evidence on the associations between SII and hepatic
steatosis and fibrosis, it lacks a comprehensive discussion on how these findings could be
incorporated into clinical practice or influence screening strategies. The current conclusions
highlight SII's potential utility, but practical guidance for clinicians is missing.
4. The manuscript does not provide clarity on whether the patients in the study cohort have pre-
existing liver disease, nor does it specify the types of liver disease present . In addition, we don't
know how many of the patients in the cohort have other inflammatory diseases  such as RA
or SLE, for example.  This is a significant limitation, as the behavior of the Systemic Immune
Inflammation Index (SII) may vary across different liver disease/systemic disease etiologies.
5. The manuscript does not address whether patients with cirrhosis are included in the study
cohort. This omission is important, as the Systemic Immune Inflammation Index (SII) may
behave differently in cirrhotic patients compared to those with non-cirrhotic liver disease.
Please review this paper.
user
Title: Differential effects of systemic immune inflammation indices on hepatic steatosis and
hepatic fibrosis: evidence from NHANES 1999-2018
Version: 0 Date: 18 Nov 2024
Reviewer's report:
This cross-sectional study by Shuyin et al. analyzed data from 21,833 NHANES participants to
investigate the relationship between the Systemic Immune Inflammation Index (SII) and hepatic
fibrosis/steatosis. Using multiple biomarkers, the research revealed a negative association
between SII and hepatic fibrosis, while finding a positive association with hepatic steatosis. The
study utilized complex statistical methods including Pearson's correlation, generalized linear
models, and restricted cubic splines. The findings suggest SII could be a cost-effective, easily
obtainable marker for assessing liver health. The results highlight the complex interplay between
systemic inflammation and liver pathology. Despite being well written and intriguing study,
there are some comments that needs to be addressed:
1.  The manuscript provides valuable insights into the relationship between the Systemic Immune
Inflammation Index (SII) and hepatic steatosis and fibrosis. However, the study misses an
important opportunity to compare SII with other well-established inflammation markers such as
CRP, ESR and WBC. These biomarkers are frequently used in clinical practice to assess systemic
inflammation. It would be important to analyze whether these traditional markers demonstrate
similar associations with hepatic steatosis and fibrosis as observed with SII. This comparison
would strengthen the argument for using SII as a preferred marker.
2. The study relies on non-invasive biomarkers. While these indices are valuable, the lack of
data from more direct diagnostic tools such as abdominal ultrasound for steatosis evaluation,
FibroScan for fibrosis evaluation, or liver biopsy for both limits the robustness of the findings.
Including data from these modalities would provide a more comprehensive validation of the
observed associations and offer insights into the diagnostic accuracy of SII compared to
established imaging and histological methods.
3. While the manuscript provides some evidence on the associations between SII and hepatic
steatosis and fibrosis, it lacks a comprehensive discussion on how these findings could be
incorporated into clinical practice or influence screening strategies. The current conclusions
highlight SII's potential utility, but practical guidance for clinicians is missing.
4. The manuscript does not provide clarity on whether the patients in the study cohort have pre-
existing liver disease, nor does it specify the types of liver disease present . In addition, we don't
know how many of the patients in the cohort have other inflammatory diseases  such as RA
or SLE, for example.  This is a significant limitation, as the behavior of the Systemic Immune
Inflammation Index (SII) may vary across different liver disease/systemic disease etiologies.
5. The manuscript does not address whether patients with cirrhosis are included in the study
cohort. This omission is important, as the Systemic Immune Inflammation Index (SII) may
behave differently in cirrhotic patients compared to those with non-cirrhotic liver disease.
assistant