Correspondence to letter to the editor 1 on “Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma”

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Clin Mol Hepatol. 2025;31(1):e96-e97
Publication date (electronic) : 2024 November 11
doi : https://doi.org/10.3350/cmh.2024.0999
1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
2Department of Health Service Administration, College of Public Health, China Medical University, Taichung, Taiwan
3Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
4School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
5Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Corresponding author : Chien-Wei Su Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd., Peitou District, Taipei 11217, Taiwan Tel: +886-2-28712121 ext. 3352, Fax: +886-2-28739318, E-mail: cwsu2@vghtpe.gov.tw
Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea
Received 2024 November 6; Accepted 2024 November 7.

Dear Editor,

We wish to extend our sincere gratitude to Zhanna Zhang and Gongqiang Wu for their valuable suggestions and thoughtful insights regarding our recent work [1]. We are pleased to engage in further discussion on our methodology and findings [2].

First, Zhang et al. raised an important concern regarding multicollinearity, particularly with the inclusion of composite variables such as serum biomarker scores, including the albumin-bilirubin (ALBI) score, lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI). We fully acknowledge and share this concern, which is central to our study’s context: employing machine learning-based methods to enhance model performance and address issues like overfitting and multicollinearity. LASSO-Cox regression has been widely demonstrated as an effective method for variable selection, with the capacity to reduce overfitting and mitigate multicollinearity [3,4]. Consequently, we employed LASSO-Cox regression, and our CATS-INF score showed slightly improved performance compared to models developed using conventional methods. Based on these findings, we are confident that multicollinearity posed minimal concern in our study.

Second, Zhang et al. raised concerns about the potential limitations related to the follow-up duration, particularly given the favorable prognosis of early-stage hepatocellular carcinoma (HCC). While it is true that follow-up duration could be considered a limiting factor, our cohort had a median follow-up period of 38.0 months, which aligns with the methods and durations used in other well-regarded studies [5-7]. Additionally, we conducted further analyses involving HCC patients across all stages in a subsequent study, which yielded consistent results [8]. Therefore, we believe that the follow-up duration and stage-specific limitations are unlikely to have significantly affected our findings. Nonetheless, we agree that future research with longer follow-up periods would be beneficial.

We sincerely appreciate the comments from Zhang et al. and hope our response addresses their concerns effectively. Machine learning has significantly advanced survival analysis for patients with various diseases [9]. Additionally, it has been applied in evaluating non-fatal outcomes, such as the failure of direct-acting antivirals in hepatitis C virus patients [10]. We hope our responses illustrate our commitment to advancing the evaluation of HCC prognosis and contributing to personalized patient care.

Notes

Authors’ contribution

Conceptualization, E C-H Tan and C-W Su; Original draft, C-T Ho; Review and editing, C-W Su.

Conflicts of Interest

There are no potential conflicts of financial and non-financial interests in the study. Chien-Wei Su: Speakers’ bureau: Gilead Sciences, Bristol-Myers Squibb, AbbVie, Bayer, and Roche. Advisory arrangements: Gilead Sciences. Grants: Bristol-Myers Squibb and Eiger.

Abbreviations

ALBI

albumin-bilirubin

HCC

hepatocellular carcinoma

LMR

lymphocyte-to-monocyte ratio

PNI

prognostic nutritional index

References

1. Zhang Z, Wu G. Insights on risk score development: Considerations for early-stage hepatocellular carcinoma models. Clin Mol Hepatol 2025;31:e8–e9.
2. Ho CT, Tan EC, Lee PC, Chu CJ, Huang YH, Huo TI, et al. Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma. Clin Mol Hepatol 2024;30:406–420.
3. Li H, Zhou C, Wang C, Li B, Song Y, Yang B, et al. Lasso-cox interpretable model of AFP-negative hepatocellular carcinoma. Clin Transl Oncol 2024;Jul. 4. doi: 10.1007/s12094-024-03588-0.
4. Zhang R, Li C, Zhang S, Kong L, Liu Z, Guo Y, et al. UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL. Clin Mol Hepatol 2024;30:771–792.
5. Ho CT, Chia-Hui Tan E, Lee PC, Chu CJ, Huang YH, Huo TI, et al. Prognostic nutritional index as a prognostic factor for very early-stage hepatocellular carcinoma. Clin Transl Gastroenterol 2024;15:e00678.
6. Tsai FP, Su TH, Huang SC, Tseng TC, Hsu SJ, Liao SH, et al. Outcomes of radiofrequency ablation for hepatocellular carcinoma with concurrent steatotic liver disease. Cancer 2024;Sep. 6. doi: 10.1002/cncr.35541.
7. Rich NE, Jones PD, Zhu H, Prasad T, Hughes A, Pruitt S, et al. Impact of racial, ethnic, and socioeconomic disparities on presentation and survival of HCC: a multicenter study. Hepatol Commun 2024;8:e0477.
8. Ho CT, Su CW, Tan ECH, Huang YH, Hou MC, Wu JC. SAT-484 conventional and machine-learning based risk score on survival for patients with hepatocellular carcinoma. J Hepatol 2024;80:S398.
9. Ho CT, Tan EC, Su CW. Correspondence to editorial on “Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma”. Clin Mol Hepatol 2024;30:1016–1018.
10. Lu MY, Huang CF, Hung CH, Tai CM, Mo LR, Kuo HT, et al. Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: a nationwide hepatitis C virus registry program. Clin Mol Hepatol 2024;30:64–79.

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