Letter to the Editor: Serum chitinase-3-like protein 1 as a biomarker in liver disease: Concerns regarding postoperative recurrence and hepatitis-related confounding

Abstract

With great interest, we read the article by Zhang et al entitled “Diagnostic value of serum chitinase-3-like protein 1 for liver fibrosis/cirrhosis and hepatocellular carcinoma” published in the World Journal of Gastrointestinal Oncology. This retrospective study evaluated the diagnostic and prognostic value of serum chitinase-3-like protein 1 (CHI3 L1) in liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and postoperative recurrence. We commend the authors for their important contribution in developing a novel serological biomarker for liver diseases. However, there are still several issues that need to be addressed in this study. The study suggests that serum CHI3 L1 can be used to monitor patients after hepatectomy and identify postoperative recurrence. However, it may be necessary to provide and compare serum CHI3 L1 data from HCC patients after curative resection (without recurrence) with the serological data from patients with postoperative recurrence, to better support this conclusion. In this study, patients with cirrhosis, HCC and postoperative recurrence were included. These populations are frequently accompanied by underlying hepatitis, which may affect serum CHI3 L1 levels and potentially confound the results. This overlap in disease etiologies and inflammatory activity might also help explain the relatively low diagnostic performance observed in the receiver operating characteristic analysis shown in Figure 1.

Key Words: Chitinase-3-like protein 1; Viral hepatitis; Non-viral hepatitis; Liver cirrhosis; Hepatocellular carcinoma

Core Tip: Serum chitinase-3-like protein 1 (CHI3L1) is a promising biomarker for liver fibrosis, cirrhosis, hepatocellular carcinoma, and postoperative recurrence. However, its value for recurrence surveillance would be better supported by comparing postoperative CHI3L1 levels between patients with and without recurrence after curative resection. In addition, underlying hepatitis and inflammatory activity may influence serum CHI3L1 levels and confound diagnostic performance. These factors should be considered when interpreting the clinical utility of CHI3L1 in liver disease.

TO THE EDITOR

With great interest, we read the article by Zhang et al[1] entitled “Diagnostic value of serum chitinase-3-like protein 1 for liver fibrosis/cirrhosis and hepatocellular carcinoma” published in the World Journal of Gastrointestinal Oncology. This retrospective study evaluated the diagnostic and prognostic value of serum chitinase-3-like protein 1 (CHI3 L1) in liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and postoperative recurrence. A total of 551 patients with viral hepatitis, non-viral hepatitis, cirrhosis, HCC, post-resection HCC, and recurrent HCC, as well as healthy controls, were enrolled. Serum CHI3 L1 levels were significantly elevated in cirrhosis, HCC, and recurrence groups and increased progressively with disease severity, while levels decreased after curative resection. ROC analysis showed good diagnostic performance of CHI3 L1 for cirrhosis [area under the curve (AUC) = 0.874], HCC (AUC = 0.858), and HCC recurrence (AUC = 0.723). CHI3 L1 was positively correlated with liver stiffness measurement and the FIB-4 index, and could distinguish advanced fibrosis stages (F3 vs F4). Combined with FIB-4 or AFP, its diagnostic accuracy further improved. These findings indicate that serum CHI3 L1 is a reliable, non-invasive biomarker for staging liver fibrosis, diagnosing HCC, and monitoring postoperative recurrence and prognosis. However, there are still several issues that need to be addressed in this study.

The study suggests that serum CHI3 L1 can be used to monitor patients after hepatectomy and identify postoperative recurrence. However, it may be necessary to provide and compare serum CHI3 L1 data from HCC patients after curative resection (without recurrence) with the serological data from patients with postoperative recurrence, to better support this conclusion.

In this study, patients with cirrhosis, HCC and postoperative recurrence were included. These populations are frequently accompanied by underlying hepatitis, which may affect serum CHI3 L1 levels and potentially confound the results[2]. This overlap in disease etiologies and inflammatory activity might also help explain the relatively low diagnostic performance observed in the ROC analysis shown in Figure 1. In summary, we commend the authors for their important contribution in developing a novel serological biomarker for liver diseases.

Figure 1 Receiver operating characteristic curve analysis of the diagnostic efficacy of serum chitinase-3-like protein 1 on hepatocellular carcinoma and liver cirrhosis[1]. Citation: Zhang H, Zhang R, Jia Y, Liu Y, Zhu L, Liu F, Rao H. Diagnostic value of serum chitinase-3-like protein 1 for liver fibrosis/cirrhosis and hepatocellular carcinoma. World J Gastrointest Oncol 2026; 18: 116821. Copyright© The Authors 2026. Published by Baishideng Publishing Group. AUC: Area under the curve.