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: 01 Apr 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The manuscript does not mention the sample size or the power analysis conducted for the study.
A detailed discussion of the sample size, including the rationale for the size, would strengthen
the credibility of the study's conclusions. If the sample size is small, there may be concerns about
the statistical power of the findings.
-Some exclusion criteria may be overly restrictive. For instance, excluding patients with
comorbidities like hyperlipidemia, which could impact lipid metabolism, might limit the
generalizability of the results. While the exclusion of patients with other etiologies (e.g., drug-
induced liver failure) is understandable, it would be helpful to address why such exclusions were
necessary in more detail.
-The relationship between lipid metabolism and immune dysfunction is stated but not deeply
explored in the literature review or the introduction. A more in-depth discussion on how
lipid metabolism disorders affect immune function would provide readers with a clearer
understanding of the biological mechanisms involved.
-The study design is retrospective, and while it analyzes the relationship between lipid
metabolism and prognosis, it lacks a detailed longitudinal follow-up that could offer more insight
into the progression of lipid metabolism changes over time. A prospective study could provide
more conclusive evidence.
-The analysis does not seem to sufficiently account for potential confounding factors (e.g.,
medications, pre-existing conditions, lifestyle factors) that could influence lipid metabolism and
immune function. While multivariate analyses have been used, further clarification of the model
selection process and the variables included would be helpful.
-The study references conflicting results from prior studies (e.g., the contradictory finding
on HDL-C levels from Etogo-Asse et al.), but it does not adequately address why those
discrepancies exist or explore potential reasons for the differences in the results. A more
thorough discussion of the limitations and variations between studies would be beneficial.
-While statistical methods are outlined, a more detailed explanation of why each method was
chosen and how potential biases (e.g., survival bias, selection bias) were controlled for would
improve the transparency and rigor of the study. For instance, Kaplan-Meier survival analysis
should include a mention of potential stratification factors or a discussion on censoring.
-Although lipid metabolism is a key aspect of the study, the research might benefit from a broader
look at other metabolic and immune factors (such as inflammatory cytokines, and liver fibrosis
stages) that may be crucial in the prognosis of HBV-ACLF. By solely focusing on lipid markers,
the study might miss out on other critical contributors to disease outcomes.
-While the discussion provides insights into the findings, there is limited reference to the
statistical methods used to analyze these results in the context of the discussion. For example,
it would be helpful to include a brief recap of the statistical significance of key findings (e.g.,
the p-values for differences between the deceased and survivor groups), which would provide
further clarity and reinforce the reliability of the conclusions.
-While the study acknowledges the potential impact of bacterial infections and other systemic
responses, it would benefit from a more detailed discussion of how these confounders were
controlled in the analysis. Although bacterial infections are mentioned as a contributing factor
to lipid metabolism disorders, the study could explore the impact of specific treatments (e.g.,
antibiotics, antiviral therapy) on lipid metabolism and immune function in more detail.
-The discussion hints at the potential for regulating lipid metabolism to improve immune
function in HBV-ACLF patients, but it does not explore in-depth therapeutic strategies. How
might clinicians utilize these findings in practice? Would lipid-modifying therapies (e.g., statins)
be beneficial in this patient population? Expanding on these clinical implications would provide
practical value to the research.
-While bacterial infections are an important contributor to the progression of ACLF, the paper
places substantial emphasis on their role in exacerbating lipid metabolism disorders. While this is
a valid finding, it could detract from the main focus on lipid metabolism itself. A more balanced
approach would ensure that the main topic of lipid metabolism in HBV-ACLF remains central.
-The discussion mentions the concept of T-cell exhaustion but does not explore the detailed
mechanisms involved. Given the importance of immune dysfunction in HBV-ACLF, a deeper
dive into how metabolic alterations affect T-cell function (e.g., glycolysis vs. oxidative
phosphorylation) would enrich the reader's understanding of this aspect of the study.