Correspondence on Letter regarding “Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF-κB signaling pathways”

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Clin Mol Hepatol. 2023;29(1):171-172
Publication date (electronic) : 2022 November 10
doi :
1Department of Translational Medicine, Graduate School of Biomedical Science & Engineering, Hanyang University, Seoul, Korea
2Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
Corresponding author : Dae Won Jun Department of Internal Medicine, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea Tel: +82-2-2290-8338, Fax: +82-2-972-0068, E-mail:
Editor: Seung Up Kim, Yonsei University College of Medicine, Korea
Received 2022 November 6; Accepted 2022 November 7.

Dear Editor,

We appreciate your interest in our study. As pointed out by Liu and Chen [1], non-alcoholic fatty liver disease (NAFLD) has a broad heterogeneous spectrum and a diverse pathophysiology [2-8]. The relationship between auranofin-induced ferroptosis and NAFLD is somewhat complex [9]. It depends on the cell type and disease condition. Ferroptosis is associated with the pathogenesis of NAFLD, and inhibiting ferroptosis can inhibit necrotic cell death, inflammatory cell infiltration, and inflammatory cytokine expression in early-stage NAFLD [9]. However, in late-stage NAFLD and hepatocellular carcinoma, inhibition of ferroptosis is associated with disease progression [10,11]. In previous studies, the expression of glutathione peroxidase (GPX) 4, which protects cells against membrane lipid peroxidation, has been shown to vary according to the severity of NAFLD. In addition, the association between ferroptosis and NAFLD has been observed to vary depending on the animal model of NAFLD. This indicates that ferroptosis may play various roles at different stages of NAFLD. System Xc and NAFLD also share a complex relationship. A large body of evidence suggests that auranofin induces ferroptosis via the cystineglutamate antiporter system Xc. Auranofin has been shown to induce ferroptosis via the GSH/GPX axis. Additionally, our previous study indicated that auranofin inhibited system Xc in macrophages and the NOD-like receptor family pyrin domain containing 3 inflammasome in inflammatory cells [12]. However, ferroptosis can simultaneously induce iron-dependent lipid peroxidation. Yang et al. [13] demonstrated that auranofin at high doses (25 mg/kg) induces ferroptosis but causes lipid peroxidation by inhibiting thioredoxin reductase activity. In conclusion, it is evident that auranofin acts as an inhibitor of system Xc. However, ferroptosis induced by system Xc inhibitors appears to play a different role in disease progression depending on the liver cell type and severity of NAFLD. Therefore, for the clinical application of auranofin, it is important to select a target population that is anticipated to have a positive therapeutic effect.


Authors’ contribution

All authors contributed in conception of the work and drafting of the article. All authors provided final approval of the version to be published.

Conflicts of Interest

The authors have no conflicts to disclose.



glutathione peroxidase


non-alcoholic fatty liver disease


1. Liu Y, Chen M. Repurposing auranofin in nonalcoholic fatty liver disease still requires further evidence. Clin Mol Hepatol 2023;29:163–164.
2. Kim HY. Recent advances in nonalcoholic fatty liver disease metabolomics. Clin Mol Hepatol 2021;27:553–559.
3. Nam HH, Jun DW, Jeon HJ, Lee JS, Saeed WK, Kim EK. Osthol attenuates hepatic steatosis via decreased triglyceride synthesis not by insulin resistance. World J Gastroenterology 2014;20:11753–11761.
4. Kang SH, Lee HW, Yoo JJ, Cho Y, Kim SU, Lee TH, et al. KASL clinical practice guidelines: management of nonalcoholic fatty liver disease. Clin Mol Hepatol 2021;27:363–401.
5. Ting YW, Kong AS, Zain SM, Chan WK, Tan HL, Mohamed Z, et al. Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: results from a multi-ethnic Asian cohort. Clin Mol Hepatol 2021;27:486–498.
6. Ikejima K, Kon K, Yamashina S. Nonalcoholic fatty liver disease and alcohol-related liver disease: from clinical aspects to pathophysiological insights. Clin Mol Hepatol 2020;26:728–735.
7. Soon G, Wee A. Updates in the quantitative assessment of liver fibrosis for nonalcoholic fatty liver disease: histological perspective. Clin Mol Hepatol 2021;27:44–57.
8. Kim KS, Lee BW. Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease. Clin Mol Hepatol 2020;26:430–443.
9. Wang S, Liu Z, Geng J, Li L, Feng X. An overview of ferroptosis in non-alcoholic fatty liver disease. Biomed Pharmacother 2022;153:113374.
10. Chen J, Li X, Ge C, Min J, Wang F. The multifaceted role of ferroptosis in liver disease. Cell Death Differ 2022;29:467–480.
11. Kumar R, Goh BG, Kam JW, Chang PE, Tan CK. Comparisons between non-alcoholic steatohepatitis and alcohol-related hepatocellular carcinoma. Clin Mol Hepatol 2020;26:196–208.
12. Kim HY, Choi YJ, Kim SK, Kim H, Jun DW, Yoon K, et al. Auranofin prevents liver fibrosis by system Xc-mediated inhibition of NLRP3 inflammasome. Commun Biol 2021;4:824.
13. Yang L, Wang H, Yang X, Wu Q, An P, Jin X, et al. Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms. Signal Transduct Target Ther 2020;5:138.

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