Dear Editor,
We acknowledge and concur with the Editorial regarding the importance of the surveillance of both cardiometabolic risk factors (CMRFs) and concurrent steatotic liver disease (SLD) in chronic hepatitis C (CHC) before and after viral eradication [
1]. The authors proposed an algorithm that enables holistic care after hepatitis C virus (HCV) eradication from both metabolic and hepatic aspects. While the European Association for the Study of the Liver (EASL) has advocated the last version regarding the treatment of HCV infection in 2020 [
2], the authors denoted an updated EASL position statement with respect to the post-HCV cure follow-up [
3]. It highlighted the importance of identifying metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with borderline advanced liver fibrosis (liver stiffness of 8–10 kPa or fibrosis-4 index of 1.45–3.25), of whom diet and lifestyle modification and continuous fibrosis assessment are warranted. Notably, the statement was based on the status before antiviral therapy. As the two components of MASLD, SLD and CMRF, would evolve after HCV eradication, the dynamic change of MASLD status should be taken into consideration [
4].
Critically, accompanied with the new definition of MASLD, it remains unclear whether SLD or CMRF contributes more to the development of hepatocellular carcinoma (HCC) in the post-sustained virological response (SVR) era. We collected 1,120 biopsy-proven CHC patients and observed a trajectory relationship between hepatic steatosis and liver fibrosis (
Fig. 1). The proportion of hepatic steatosis increased with the progression of fibrotic stage from F0 (20%), F1 (40%) to F2 (63%), indicating a potential lipotoxicity effect in fibrogenesis. Nevertheless, the proportion of hepatic steatosis started to decrease from F3 (55%) to F4 (41%), which might be attribute to burnout phenomenon (
Fig. 1). While we adopt cross-sectional hepatic steatosis as the baseline variable to judge the longitudinal long-term outcome, it is hard to avoid and adjust the most critical confounder of HCC, the dynamic progression of liver fibrosis. On the other hand, the other component of MASLD, CMRF, possesses a mutual link with SLD [
5]. We have recently demonstrated that liver disease severity increased with the increasing number of CMRFs carriage in CHC patients with MASLD [
6]. Amongst the CMRFs, insulin resistance and diabetes are the major determinants for HCC in CHC and other etiologies [
7,
8], which are also the driving force for hepatic steatosis. Under the circumstances, SLD may be a bystander rather than a direct insult for hepatocarcinogesis. With the emergent definition of MASLD and its evolution after HCV eradication, its relationship with HCC in the post-SVR era adds complexity and awaits clarification. In addition, subjects with MASLD are prone to have metabolic disarrangements. The frequent use of aspirin, metformin and statin as the chemoprevention of HCC also needs to be judged [
9-
11]. Taken collectively, further studies are warranted to address the impact of pre- and post-SVR MASLD on HCC by weighting coexistent CMRFs and liver fibrosis.
FOOTNOTES
-
Authors’ contribution
Conception and design: Ming-Lung Yu. Acquisition of data: Chung-Feng Huang, Chia-Yen Dai, Ming-Lun Yeh, Jee-Fu Huang, Wan-Long Chuang and Ming-Lung Yu. Data analysis and interpretation: Chung-Feng Huang and Ming-Lung Yu. Manuscript drafting and critical revision: Chung-Feng Huang, Jee-Fu Huang and Ming-Lung Yu. Approval of the final version of the manuscript: Jee-Fu Huang and Ming-Lung Yu.
-
Conflicts of Interest
The authors have no conflicts to disclose.
Figure 1.Association of hepatic steatosis and liver fibrosis in 1,120 biopsy-proven chronic hepatitis C patients. S0-3, hepatic steatosis grade 0-3; F0-4, fibrotic stage 0-4.
Abbreviations
cardiometabolic risk factor
European Association for the Study of the Liver
metabolic dysfunction-associated steatotic liver disease
sustained virological response
REFERENCES
- 1. MASLD after hepatitis C virus eradication: Do not overlook the cardiometabolic risk factors: Editorial on “Dynamic change of metabolic dysfunction-associated steatotic liver disease in chronic hepatitis C patients after viral eradication: A nationwide registry study in Taiwan”. Clin Mol Hepatol 2025;31:290-292.
- 2. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C: Final update of the series. J Hepatol 2020;73:1170-1218.
- 3. Reiberger T, Lens S, Cabibbo G, Nahon P, Zignego AL, Deterding K, et al. EASL position paper on clinical follow-up after HCV cure. J Hepatol 2024;81:326-344.
- 4. Huang CF, Dai CY, Lin YH, Wang CW, Jang TY, Liang PC, et al. Dynamic change of metabolic dysfunction-associated steatotic liver disease in chronic hepatitis C patients after viral eradication: A nationwide registry study in Taiwan. Clin Mol Hepatol 2024;30:883-894.
- 5. Yeh ML, Huang JF, Dai CY, Huang CF, Yu ML, Chuang WL. Metabolic dysfunction-associated steatotic liver disease and diabetes: the cross-talk between hepatologist and diabetologist. Expert Rev Gastroenterol Hepatol 2024;18:431-439.
- 6. Huang CF, Yeh ML, Dai CY, Huang JF, Chuang WL, Yu ML. Chronic hepatitis C related steatotic liver disease is more than “Miscellaneous Steatotic Liver Disease”. Clin Gastroenterol Hepatol 2024;22:2137-2139 e2.
- 7. Nakatsuka T, Tateishi R. Development and prognosis of hepatocellular carcinoma in patients with diabetes. Clin Mol Hepatol 2023;29:51-64.
- 8. Huang CF, Yeh ML, Huang CY, Tsai PC, Ko YM, Chen KY, et al. Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy. Medicine (Baltimore) 2016;95:e4157.
- 9. Goh MJ, Sinn DH. Statin and aspirin for chemoprevention of hepatocellular carcinoma: Time to use or wait further? Clin Mol Hepatol 2022;28:380-395.
- 10. Tsai PC, Huang CF, Yeh ML, Hsieh MH, Kuo HT, Hung CH, et al. Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy. Clin Mol Hepatol 2024;30:468-486.
- 11. Tsai PC, Kuo HT, Hung CH, Tseng KC, Lai HC, Peng CY, et al. Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan. J Hepatol 2023;78:281-292.
Citations
Citations to this article as recorded by
- Hepatocellular carcinoma surveillance after sustained virological response in chronic hepatitis C: Editorial on “Non-invasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus: A systematic review and meta-ana
Ho Soo Chun, Minjong Lee
Clinical and Molecular Hepatology.2025; 31(1): 261. CrossRef - Hepatitis C virus and cardiovascular disease: Current knowledge and unmet needs
Chih-Wen Wang, Jee-Fu Huang, Ming-Lung Yu, Wan-Long Chuang
Tzu Chi Medical Journal.2025; 37(4): 371. CrossRef
, Wan-Long Chuang1,2, Ming-Lung Yu1,2,4
