Review for 10.1186/s12876-025-04004-9 (2025)

Title: Lipid Metabolism Disturbance and Immune Dysfunction in HBV-Related Acute-on-
Chronic Liver Failure: A Retrospective Cohort Study
Version: 3 Date: 05 Apr 2025
Reviewer:  Amira A. A. Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Wang et al. aimed to investigates
the relationship between lipid metabolism disorders, peripheral immunity, and prognosis in
patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Using a
retrospective cohort of 803 patients, the authors found that decreased levels of HDL-C, LDL-C,
TG, TC, APOA1, and APOB were associated with immune dysfunction and disease severity.
APOA1 and APOB were identified as independent protective factors against 90-day mortality.
The study concludes that lipid metabolism dysregulation contributes to HBV-ACLF progression
by modulating immune responses.
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The language is generally straightforward, but minor grammatical errors and awkward
phrasings could be improved. Consider having the manuscript proofread by a native English
speaker or a professional editing service.
2. Abbreviations must be fully written at their first appearance.
In Title:
1. The current title is descriptive but could be more concise. Make the title more specific by
including the main variable, study type, or key finding. I suggest [Lipid Metabolism Disorders
and Immune Dysfunction in HBV-Associated Acute-on-Chronic Liver Failure: A Retrospective
Cohort Study].
In the Abstract section
2. Missing absolute values for lipid markers (e.g., mean/median levels in survivors vs. non-
survivors). Add the [Mean HDL-C: 0.8 mmol/L (survivors) vs. 0.5 mmol/L (non-survivors).]
3. The HRs for APOA1/APOB are repeated ("HR=0.313" appears twice). Correct to be [APOA1:
HR=0.246 (95% CI: 0.110–0.547); APOB: HR=0.313 (95% CI: 0.173–0.567).]
In the Introduction section:
4. Despite citing prior research on lipid-ACLF links, the uniqueness of the study is still unclear.
5. Does not state the hypothesis.
In the Methods section:
6. Reword Inclusion/Exclusion Criteria, duplicate exclusion criteria (e.g., HIV coinfection listed
twice).
7. No justification for Spearman over Pearson correlation (non-normal data?)
8. How were ACLF stages (early/intermediate/advanced) defined?
In the Results section:
9. In all tables, please explain the abbreviations in tables.
10. Table 1: "CD4+T/CD8+T ratio" is mentioned as non-significant (P > 0.05) but later called
significant (P < 0.05). Correct the inconsistency. Also, Units missing for lab values (e.g., TBIL
in µmol/L or mg/dL?).
11. Figure 2, 3: No p-values for subgroup comparisons (e.g., MELD strata).
12. Figure 4: ROC curves lack AUC comparisons (e.g., APOA1 vs. MELD).
In the Discussion section:
13. State that : [APOA1/APOB may reflect synthetic liver function rather than direct immune
modulation].
14. Does not address confounding by malnutrition [low lipids may reflect poor nutrition, not
just liver failure].
15. Add a proper discussion of the study’s limitations [Lipid-lowering therapies, Dynamic
changes in lipids/immune cells during hospitalization were not assessed].
16. Critically analyze how these findings compare to previous studies.
17. Cite recent literature to strengthen your argument.
In the Conclusion section:
18. "Make the conclusion more specific; summarize the key findings without overgeneralizing.
19. Avoid speculation and suggest future research areas if relevant.