Correspondence to letter to the editor 1 on “Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study”

Article information

Clin Mol Hepatol. 2025;31(2):e208-e209

Publication date (electronic) : 2025 January 6

doi : https://doi.org/10.3350/cmh.2024.1171

Seogsong Jeong^1,2, Won Kim^,3,4, Sang Min Park^,5,6

¹Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea

²Biomedical Research Center, Korea University Guro Hospital, Seoul, Korea

³Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea

⁴Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

⁵Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea

⁶Departmenet of Family Medicine, Seoul National University Hospital, Seoul, Korea

Corresponding author : Sang Min Park Department of Family Medicine and Biomedical Sciences, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-3331, Fax: +82-2-766-3276, E-mail: smpark.snuh@gmail.com

Won Kim Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea Tel: +82-2-870-2233, Fax: +82-2-831-2826, E-mail: drwon1@snu.ac.kr

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

Received 2024 December 23; Accepted 2025 January 2.

Dear Editor,

We extend our gratitude to Xu et al. [1] for their perceptive observations. The initial remark pertained to the retrospective design of the Korea National Health Insurance Service (NHIS) cohort research. To mitigate the potential for reverse causality, our investigation into the evolutionary alterations in metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of hepatocellular carcinoma (HCC) conducted sensitivity analyses by excluding HCC occurrences within 1, 3, and 5 years from the initial follow-up date [2]. This strategy, while unable to entirely eradicate reverse causality, is commonly employed in the assessment of chronic outcomes like cancer and dementia [3].

Secondly, we concur that employing the fatty liver index to delineate MASLD may have created bias, given that the NHIS population lacks imaging or liver biopsy data. This method may elevate the false-positive rate while diminishing specificity; hence, utilizing ultrasonography or transient elastography to define hepatic steatosis may be optional for assessing the dynamic changes of MASLD [4]. Conversely, it aids in identifying undiagnosed patients, thus enhancing the false-negative rate. Indeed, a significant number of epidemiological research have employed the fatty liver index within the NHIS sample [5-9].

Thirdly, this study did not consider genetic risk, liver fibrosis, or gut microbiome owing to the lack of pertinent data. Subsequent research with more extensive information may also consider these confounding variables. Moreover, the study population comprised individuals undergoing health screening checks, who are likely to be more health-conscious. Future study focusing on groups that do not participate in regular health screenings may be essential to elucidate the relationship between alterations in MASLD and the risk of HCC.

The underlying processes contributing to the heightened risk of HCC in individuals with resolved MASLD remain ambiguous. We recognize that prior liver damage or subclinical fibrosis may exacerbate this increased risk. Furthermore, patients with hepatic steatosis who had recuperated from metabolic dysfunctions were classified as having resolved MASLD. Consequently, low-grade chronic liver inflammation may endure and represent a significant residual risk factor for HCC.