Reply to correspondence on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”

Article information

Clin Mol Hepatol. 2025;31(2):e232-e233

Publication date (electronic) : 2025 February 26

doi : https://doi.org/10.3350/cmh.2025.0203

Chen-Hua Liu^,¹^,²^,³

, Yu-Ping Chang ⁴

¹Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

²Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

³Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan

⁴Department of Internal Medicine, National Taiwan University Biomedical Park Hospital, Hsin-Chu, Taiwan

Corresponding author : Chen-Hua Liu Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 10002, Taiwan Tel: +886-2-23123456 ext 63572, Fax: +886-2-23825962, E-mail: jacque_liu@mail2000.com.tw

Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea

Received 2025 February 21; Accepted 2025 February 22.

See the Original "Correspondence to editorial on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”" on page e203.

Keywords: Hepatitis C; Hepatic fibrosis; Noninvasive test; Sustained virologic response; Direct-acting antiviral

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].

Notes

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

DAA

direct-acting antiviral

FIB-4

fibrosis index based on four parameters

GEE

generalized estimating equations

GLMM

generalized linear mixed model

HCC

hepatocellular carcinoma

HCV

hepatitis C virus

LSM

liver stiffness measurement

MRE

magnetic resonance elastography

SVR

sustained virologic response

THR-β

thyroid hormone receptor-beta

VCTE

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.

4. Liu J, Colditz GA. Optimal design of longitudinal data analysis using generalized estimating equation models. Biom J 2017;59:315–330.

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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