Dear Editor,
We fully agree with Ryu et al.’s work, as well as their correspondence regarding our opinions on the potential interest in evaluating hepatic fibrosis dynamics and long-term liver-related outcomes among individuals who attain sustained virologic response (SVR) following direct-acting antivirals (DAAs) for hepatitis C virus (HCV) [
1-
3].
Apart from the short-term improvement of the fibrosis index based on four parameters (FIB-4) and liver stiffness measurements (LSMs) using vibration-controlled transient elastography (VCTE), which has been well demonstrated by the authors, it would be even more insightful to assess the long-term dynamics of serum glycemic and total cholesterol levels in relation to the time-dependent evolution of FIB-4 or LSMs, either through VCTE or magnetic resonance elastography (MRE). Preferably, this should be done using repeated measurements. This approach could help identify individuals at risk for unfavorable liver-related outcomes, such as hepatic decompensation or hepatocellular carcinoma (HCC). To better understand the complex interactions between metabolic dysfunction and hepatic fibrosis evolution at both the population and individual levels, applying generalized estimating equations (GEE) or generalized linear mixed models (GLMMs) would be beneficial [
4-
6].
In line with the authors’ comments on future research aiming to estimate the risk of insulin sensitizers or lipid-lowering agents for fibrosis regression in individuals with metabolic dysfunction following HCV cure, the role of selective thyroid hormone receptor-beta (THR-β) agonists, such as resmetirom, in mitigating or reversing hepatic fibrosis progression deserves further investigation in this population [
7].
FOOTNOTES
-
Authors’ contribution
All authors were responsible for the interpretation of data, the drafting, and the critical revision of the manuscript for important intellectual content. All authors approved the final version of the article.
-
Conflicts of Interest
The authors declare no conflicts of interest.
Abbreviations
fibrosis index based on four parameters
generalized estimating equations
generalized linear mixed model
liver stiffness measurement
magnetic resonance elastography
sustained virologic response
thyroid hormone receptor-beta
vibration-controlled transient elastography
REFERENCES
- 1. Ryu T, Chang Y, Jeong SW, Yoo JJ, Lee SH, Kim SG, et al. Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C. Clin Mol Hepatol 2025;31:548-562.
- 2. Liu CH, Chang YP. Metabolic dysfunction in patients following DAA-induced viral cure for HCV infection: A non-negligible risk to liver-related health: Editorial on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”. Clin Mol Hepatol 2025;31:658-661.
- 3. Ryu T, Chang Y, Kim SU, Jang JY. Correspondence to editorial on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”. Clin Mol Hepatol 2025;31:e203-e205.
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- 5. Liu CH, Lee MH, Lin JW, Liu CJ, Su TH, Tseng TC, et al. Evolution of eGFR in chronic HCV patients receiving sofosbuvir-based or sofosbuvir-free direct-acting antivirals. J Hepatol 2020;72:839-846.
- 6. Liu CH, Lin JW, Liu CJ, Su TH, Wu JH, Tseng TC, et al. Long-term evolution of estimated glomerular filtration rate in patients with antiviral treatment for hepatitis C virus infection. Clin Gastroenterol Hepatol 2023;21:424-434.e5.
- 7. Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med 2024;390:497-509.
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