Review for 10.1186/s12876-025-03992-y (2025)

Title: Prevalence of advanced liver fibrosis in the general population of the Paris region
according to FIB-4 score and Liver Risk Score
Version: 1 Date: 24 Mar 2025
Reviewer's report:
It is an honor to review this article, and I would like to congratulate the authors on their research.
However, I have some comments for the editors and authors to consider:
1: The study population is derived from the Paris region. How representative is this population
of the general French population or other global populations, especially considering regional
variations in lifestyle, diet, and healthcare access?
2: The study excluded patients under 18 and over 80 years old, as well as those with extreme
laboratory values. Could these exclusions potentially bias the results, particularly in terms of
underestimating the prevalence of advanced fibrosis in certain high-risk groups (e.g., elderly
patients with metabolic syndrome)?
3: The study highlights a poor correlation between FIB-4 and LRS (r=0.45). Could you elaborate
on the potential reasons for this discrepancy, and how this might impact the clinical utility of
these scores in different patient populations?
4: The FIB-4 score identified a larger number of patients requiring further evaluation compared
to LRS. What are the implications of this in terms of potential overdiagnosis, unnecessary
referrals, and healthcare costs?
5: The manuscript suggests that using LRS could reduce costs by 51%. Could you provide more
detailed data on the cost analysis, including the assumptions made and how these might vary
in different healthcare systems?
6: The study lacks clinical endpoints such as liver-related morbidity or mortality. How might
this limitation affect the interpretation of the results, particularly in terms of the predictive value
of LRS for long-term outcomes?
7: Both FIB-4 and LRS include age in their calculations, and the study found a male
predominance in advanced fibrosis. How might these factors influence the applicability of these
scores in different demographic groups, particularly in younger or female populations?
8: A significant proportion of patients with elevated FIB-4 or LRS scores had normal liver
enzymes. How should clinicians interpret these findings, and what are the implications for
current screening guidelines that rely heavily on liver enzyme levels?
9: The LRS has been validated in independent cohorts, but how robust is this validation in diverse
populations, particularly those with different etiologies of liver disease (e.g., viral hepatitis,
alcohol-related liver disease)?
10: The proposed algorithm suggests using LRS as a primary screening tool. What are the
potential barriers to implementing this algorithm in routine clinical practice, and how might
these be addressed to ensure widespread adoption?
Some additional comments and questions regarding the consideration of other non-invasive
scores, such as MAF-5 and Agile scores:
1: The manuscript focuses on FIB-4 and LRS for assessing liver fibrosis. Have the authors
considered evaluating other non-invasive scores, such as MAF-5 or Agile scores, which have
also been proposed for fibrosis assessment? Including these scores could provide a more
comprehensive comparison and potentially identify a more accurate or cost-effective tool for
screening.
2: If MAF-5 or Agile scores were considered, how do they perform in comparison to FIB-4 and
LRS in terms of sensitivity, specificity, and predictive value for advanced fibrosis? Are there
any specific patient subgroups where these scores might outperform FIB-4 or LRS?