Review for 10.1186/s12876-025-03600-z (2025)

Title: Therapeutic effects of reduced glutathione on liver function, fibrosis, and HBV DNA
clearance in chronic hepatitis b patients
Version: 3 Date: 09 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Although the study mentions that patients were divided into two groups, it does not provide
details on the randomization process or whether blinding was used in the study. Randomization
is crucial for minimizing selection bias, and blinding (either single or double) is important for
reducing performance and detection biases. Including information on whether the patients and/
or outcome assessors were blinded to the treatment allocation would strengthen the internal
validity of the study.
-The section on adverse reactions mentions the types of symptoms (nausea, vomiting, headache,
gastric discomfort), but it could benefit from further detail. For example, specifying whether
these symptoms were directly related to reduced glutathione, entecavir, or both would help
in understanding the safety profile of each treatment. Moreover, the methodology for grading
and classifying the severity of adverse events is useful, but some context or reference to a
standardized system for grading severity would clarify the approach.
-The duration of treatment (3 months) is stated, but the post-treatment follow-up periods for
assessing HBV-DNA negative conversion rates are unclear. Although there is a mention of
follow-up assessments at 4, 12, and 24 weeks, it is not clear if any longer-term follow-up
beyond this period will be conducted. Chronic hepatitis B is a long-term disease, and it would
be beneficial to include follow-up evaluations beyond 6 months to assess the durability of the
treatment effects.
-The grading system for liver fibrosis using transient elastography (FibroScan) is well defined,
but it might be helpful to provide more detail on the thresholds for each fibrosis grade, especially
for grades S0-S3, which may have more overlap in liver stiffness measurements. Including the
precise cutoffs for each grade would help clarify how these stages are differentiated and make
the study findings more interpretable for clinical practice.
-The study justifies the use of reduced glutathione as an antioxidant, but it could be more specific
in explaining its role in chronic hepatitis B treatment. For instance, does reduced glutathione
directly affect oxidative stress in hepatocytes, or does it play a role in modulating inflammation
and immune responses? A brief discussion of the hypothesized mechanisms by which GSH may
improve liver function and fibrosis would provide a stronger scientific basis for the study.
-The discussion mentions the increase in HBV-DNA negative conversion rates, but it would be
beneficial to elaborate on why this is significant from a clinical standpoint. For instance, how
does the improvement in HBV-DNA negative conversion translate to long-term benefits (e.g.,
reduced risk of cirrhosis, liver cancer, or mortality)? Additionally, while the overall effectiveness
of the therapy is discussed, more depth could be provided regarding the clinical relevance of the
fibrosis and liver function improvements. For example, what impact do these improvements in
liver fibrosis and function have on patient prognosis, survival, and quality of life?
-It would be useful to include a brief mention of how much the liver function markers improved
numerically (e.g., specific reduction in ALT and AST, or percentage change in ALB) to
give readers a clearer picture of the therapeutic impact. Additionally, while the discussion of
regression analysis is useful, the clinical significance of these findings could be expanded. For
instance, do patients in the test group show clinically meaningful improvements in daily life or
long-term outcomes as a result of the improved liver function markers?