Correspondence to letter to the editor on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”

Article information

Clin Mol Hepatol. 2025;31(1):e105-e107
Publication date (electronic) : 2024 November 4
doi : https://doi.org/10.3350/cmh.2024.0937
1Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea
2Division of Health Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency (NECA), Seoul, Korea
3Department of Internal Medicine, Hanyang University, College of Medicine, Seoul, Korea
Corresponding author : Dae Won Jun Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro Seongdong-gu, Seoul 04763, Korea Tel: +82-2-2220-8338, Fax: +82-2-2298-9183, E-mail: noshin@hanyang.ac.kr
Miyoung Choi Division of Health Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency (NECA), Namsan Square 7F, 173 Toegye-ro, Jung-gu, Seoul 04554, Korea Tel: +82-2-2174-2848, Fax: +82-2-747-4918, E-mail: mychoi@neca.re.kr
Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea
Received 2024 October 23; Accepted 2024 October 31.

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.

Demographic covariates for liver fibrosis determined by vibration-controlled transient elastography in the general population

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.

Notes

Authors’ contribution

Hee Yeon Kim, revision; Miyoung Choi, data analysis; Dae Won Jun, supervision.

Conflicts of Interest

The authors have no conflicts to disclose.

Acknowledgements

This research was supported by Korea Basic Science Institute (National research Facilities and Equipment Center) grant funded by the Ministry of Education (2023R1A6C101A009) and National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2023-00217123).

Abbreviations

VCTE

vibration-controlled transient elastography

References

1. Feng W, Wang Q, Ye Q. Letter regarding Letter regarding “Prevalence of clinically significant liver fibrosis in the general population”. Clin Mol Hepatol 2025;31:e21–e22.
2. Kim HY, Yu JH, Chon YE, Kim SU, Kim MN, Han JW, et al. Prevalence of clinically significant liver fibrosis in the general population: a systematic review and meta-analysis. Clin Mol Hepatol 2024;30(Suppl):S199–S213.
3. Niezen S, Tapper EB, Trivedi H, Lai M, Curry MP, Mukamal KJ, et al. Prevalence of high liver stiffness and a screening strategy using the SODA-2B score among US adults. Hepatol Commun 2022;6:898–909.
4. O’Hara G, Mokaya J, Hau JP, Downs LO, McNaughton AL, Karabarinde A, et al. Liver function tests and fibrosis scores in a rural population in Africa: a cross-sectional study to estimate the burden of disease and associated risk factors. BMJ Open 2020;10:e032890.
5. Watt GP, Lee M, Pan JJ, Fallon MB, Loomba R, Beretta L, et al. High prevalence of hepatic fibrosis, measured by elastography, in a population-based study of Mexican Americans. Clin Gastroenterol Hepatol 2019;17:968–975.e5.
6. Parikh NS, Kamel H, Zhang C, Gupta A, Cohen DE, de Leon MJ, et al. Association of liver fibrosis with cognitive test performance and brain imaging parameters in the UK Biobank study. Alzheimers Dement 2023;19:1518–1528.

Article information Continued

Table 1.

Demographic covariates for liver fibrosis determined by vibration-controlled transient elastography in the general population

Covariate No. of studies Odds ratio (95% CI) Heterogeneity (I2) Meta-regression P-value R2 Prob >chi²
Significant liver fibrosis (≥F2) 22 61.54% 34.01 0.005
 Mean age 1.00 (1.00–1.00) 0.636
 Male ratio (%) 1.62 (1.21–2.16) 0.001
Advanced liver fibrosis (≥F3) 15 0.02% 0.00 0.808
 Mean age 1.00 (1.00–1.00) 0.515
 Male ratio (%) 0.98 (0.82–1.19) 0.880
Liver cirrhosis (F4) 14 0.00% 83.65 0.960
 Mean age 1.00 (1.00–1.00) 0.777
 Male ratio (%) 0.99 (0.82–1.20) 0.940

CI, confidence interval.