Title: Effect of Allostatic Load on hepatic steatosis and Fatty Liver-Associated Liver Fibrosis
Version: 3 Date: 25 Apr 2025
Reviewer's report:
Thank you for the opportunity to review the manuscript titled "Effect of Allostatic Load on
Hepatic Steatosis and Hepatic Fibrosis." While the topic of the association between allostatic
load and liver disease is of clinical interest, this manuscript has several major flaws that, in my
view, preclude publication in its current form.
Major Comments:
1. Lack of Novelty:
The study largely replicates existing findings, particularly a recent study (Dai & Zhou, BMC
Public Health, 2024) , which the authors themselves cite. The manuscript does not sufficiently
differentiate its results or approach from prior work, nor does it provide new mechanistic insights
or robust new hypotheses.
2. Methodological Concerns:
The use of NHANES data is appropriate, but the operationalization of allostatic load (ALI)
is inconsistent and problematic. Triglycerides were excluded without a fully convincing
justification, and the ALI scoring system differs from validated methods without clear validation
or sensitivity analyses to support the adaptation.
The study design is entirely cross-sectional, which the authors acknowledge, yet mediation
analyses are performed. Causal mediation analysis is inappropriate in a purely cross-sectional
design without temporal ordering.
The stratified analyses are extensive but lack clear hypothesis-driven focus, leading to the risk
of multiple testing without correction.
3. Statistical Issues:
Confidence intervals are very wide and often cross critical values, suggesting instability of
results.
Sensitivity analyses with APRI and FIB-4 fail to support the main findings, severely
undermining the robustness of the reported associations.
The adjustment models do not appear sufficient to control for residual confounding, particularly
from metabolic syndrome components closely tied to both ALI and fatty liver outcomes.
4. Language and Writing Quality:
The manuscript is difficult to read due to poor English grammar, awkward phrasing, and frequent
typographical errors (e.g., "unstable load" instead of "allostatic load" repeatedly). A major
language revision would be necessary even if the science were sound.
5. Overinterpretation of Results:
The discussion overstates the implications of the findings. For example, the claim that
"managing stress may reduce fatty liver and liver fibrosis" is speculative and unsupported by
the data presented, given the observational and cross-sectional nature of the study.
Minor Comments:
Figures and tables are not professionally formatted.
References are inconsistently formatted and include typographical errors.
Title: Effect of Allostatic Load on hepatic steatosis and Fatty Liver-Associated Liver Fibrosis
Version: 3 Date: 25 Apr 2025
Reviewer's report:
Thank you for the opportunity to review the manuscript titled "Effect of Allostatic Load on
Hepatic Steatosis and Hepatic Fibrosis." While the topic of the association between allostatic
load and liver disease is of clinical interest, this manuscript has several major flaws that, in my
view, preclude publication in its current form.
Major Comments:
1. Lack of Novelty:
The study largely replicates existing findings, particularly a recent study (Dai & Zhou, BMC
Public Health, 2024) , which the authors themselves cite. The manuscript does not sufficiently
differentiate its results or approach from prior work, nor does it provide new mechanistic insights
or robust new hypotheses.
2. Methodological Concerns:
The use of NHANES data is appropriate, but the operationalization of allostatic load (ALI)
is inconsistent and problematic. Triglycerides were excluded without a fully convincing
justification, and the ALI scoring system differs from validated methods without clear validation
or sensitivity analyses to support the adaptation.
The study design is entirely cross-sectional, which the authors acknowledge, yet mediation
analyses are performed. Causal mediation analysis is inappropriate in a purely cross-sectional
design without temporal ordering.
The stratified analyses are extensive but lack clear hypothesis-driven focus, leading to the risk
of multiple testing without correction.
3. Statistical Issues:
Confidence intervals are very wide and often cross critical values, suggesting instability of
results.
Sensitivity analyses with APRI and FIB-4 fail to support the main findings, severely
undermining the robustness of the reported associations.
The adjustment models do not appear sufficient to control for residual confounding, particularly
from metabolic syndrome components closely tied to both ALI and fatty liver outcomes.
4. Language and Writing Quality:
The manuscript is difficult to read due to poor English grammar, awkward phrasing, and frequent
typographical errors (e.g., "unstable load" instead of "allostatic load" repeatedly). A major
language revision would be necessary even if the science were sound.
5. Overinterpretation of Results:
The discussion overstates the implications of the findings. For example, the claim that
"managing stress may reduce fatty liver and liver fibrosis" is speculative and unsupported by
the data presented, given the observational and cross-sectional nature of the study.
Minor Comments:
Figures and tables are not professionally formatted.
References are inconsistently formatted and include typographical errors.
Please review this paper.
user
Title: Effect of Allostatic Load on hepatic steatosis and Fatty Liver-Associated Liver Fibrosis
Version: 3 Date: 25 Apr 2025
Reviewer's report:
Thank you for the opportunity to review the manuscript titled "Effect of Allostatic Load on
Hepatic Steatosis and Hepatic Fibrosis." While the topic of the association between allostatic
load and liver disease is of clinical interest, this manuscript has several major flaws that, in my
view, preclude publication in its current form.
Major Comments:
1. Lack of Novelty:
The study largely replicates existing findings, particularly a recent study (Dai & Zhou, BMC
Public Health, 2024) , which the authors themselves cite. The manuscript does not sufficiently
differentiate its results or approach from prior work, nor does it provide new mechanistic insights
or robust new hypotheses.
2. Methodological Concerns:
The use of NHANES data is appropriate, but the operationalization of allostatic load (ALI)
is inconsistent and problematic. Triglycerides were excluded without a fully convincing
justification, and the ALI scoring system differs from validated methods without clear validation
or sensitivity analyses to support the adaptation.
The study design is entirely cross-sectional, which the authors acknowledge, yet mediation
analyses are performed. Causal mediation analysis is inappropriate in a purely cross-sectional
design without temporal ordering.
The stratified analyses are extensive but lack clear hypothesis-driven focus, leading to the risk
of multiple testing without correction.
3. Statistical Issues:
Confidence intervals are very wide and often cross critical values, suggesting instability of
results.
Sensitivity analyses with APRI and FIB-4 fail to support the main findings, severely
undermining the robustness of the reported associations.
The adjustment models do not appear sufficient to control for residual confounding, particularly
from metabolic syndrome components closely tied to both ALI and fatty liver outcomes.
4. Language and Writing Quality:
The manuscript is difficult to read due to poor English grammar, awkward phrasing, and frequent
typographical errors (e.g., "unstable load" instead of "allostatic load" repeatedly). A major
language revision would be necessary even if the science were sound.
5. Overinterpretation of Results:
The discussion overstates the implications of the findings. For example, the claim that
"managing stress may reduce fatty liver and liver fibrosis" is speculative and unsupported by
the data presented, given the observational and cross-sectional nature of the study.
Minor Comments:
Figures and tables are not professionally formatted.
References are inconsistently formatted and include typographical errors.
assistant