Dear Editor,
We sincerely appreciate Dr. Wei Feng for showing interest in and providing valuable feedback on our recent manuscript published in Clinical and Molecular Hepatology [1]. Our study offers important insights into the prevalence of clinically significant liver fibrosis in asymptomatic populations and supports the development of screening strategies. However, as you pointed out, several challenges and points of clarification remain [2].
First, we performed a broad and comprehensive search strategy across four databases‒EMBASE, MEDLINE, Cochrane Library, and KoreaMed‒to ensure the inclusion of all relevant articles. Regarding the fours papers you identified as missing, Three were included in our initial search results but were excluded during the review of titles and abstracts for specific reasons: duplication of NHANES 2017–2018 data [3], concerns about confounding effects from human immunodeficiency virus [4], or duplication of a cohort measuring liver stiffness via vibration-controlled transient elastography (VCTE) [5]. The fourth paper, while potentially relevant, was not identified due to its title and abstract not meeting our search strategy criteria [6].
Second, we agree that the clarity of our screening criteria could be improved. We included VCTE, magnetic resonance elastography, and serum-based fibrosis scoring systems such as the fibrosis-4 index, FibroTest and the nonalcoholic fatty liver disease fibrosis score. In aiming to represent real-world clinical practice, we included patients with severe obesity and cardiovascular disease, acknowledging that these comorbidities could introduce confounding variables. While we appreciate the concern regarding potential biases from small sample sizes, our leave-oneout sensitivity analysis did not reveal significant heterogeneity, supporting the robustness of our findings.
Third, we acknowledge the heterogeneity in the pooled results for liver fibrosis prevalence. Although we initially did not perform a meta-regression analysis, we have since conducted one using mean age and male ratio as independent variables, with missing values imputed via maximum likelihood estimation. Male gender (odds ratio 1.62; 95% confidence interval 1.21–2.16; P=0.001) was associated with increased odds of significant liver fibrosis determined by VCTE among the general population. However, neither mean age nor male ratio was statistically significant for advanced liver fibrosis and liver cirrhosis (Table 1). We acknowledge the inconsistent reporting of other key variables across studies, which limited our ability to explore additional sources of heterogeneity through meta-regression. Future studies with more standardized reporting of covariates would better address this issue.
Finally, we appreciate the suggestion to report pooled odds ratios for risk factors associated with advanced liver fibrosis. While this would provide valuable quantitative insights, it was not feasible in the current study due to variability in covariate reporting. Many studies lacked adjusted odds ratios or did not consistently assess the same risk factors, limiting our ability to conduct a meta-analysis. We sincerely thank the author for their insightful comments and their thoughtful review of our work.
PDF Links
PubReader
ePub Link
XML Download
Full text via DOI
Download Citation
Print
