The identification of Chitinase-3-like protein 1 (CHI3L1) as a crucial biomarker in liver disease is revolutionizing how clinicians approach the diagnosis, monitoring, and treatment of various liver conditions. As a member of the glycoside hydrolase family 18, CHI3L1 is recognized for its unique ability to bind to ligands and influence multiple pathophysiological processes, despite lacking enzymatic activity. This distinctive protein plays a key role in mediating cell proliferation, inflammation, fibrosis, and carcinogenesis.

Liver diseases, including hepatitis-related fibrosis, non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and hepatocellular carcinoma (HCC), represent significant global health challenges. Early and accurate diagnosis is critical to managing these conditions effectively, but traditional methods such as liver biopsy are invasive and not ideal for frequent monitoring. Serum biomarkers offer a non-invasive alternative, and CHI3L1 has emerged as a reliable marker, especially for diagnosing and staging hepatic fibrosis. Elevated levels of CHI3L1 correlate with fibrosis severity, particularly in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC), where it demonstrates superior diagnostic efficacy compared to conventional markers like hyaluronic acid (HA) and FIB-4.

In addition to its diagnostic capabilities, CHI3L1 plays a significant role in evaluating fibrosis progression and monitoring the efficacy of antiviral therapies. The protein's levels increase proportionally with the advancement of liver fibrosis, making it a practical tool for assessing treatment response. Furthermore, CHI3L1 has shown promise in distinguishing between simple steatosis and non-alcoholic steatohepatitis (NASH), which is vital for identifying patients at higher risk of progressing to cirrhosis or HCC. Combining CHI3L1 with other markers, such as alpha-fetal protein (AFP) and platelet count, enhances diagnostic accuracy, particularly in detecting significant fibrosis and advanced stages of liver disease.

One of the most promising applications of CHI3L1 is its potential to predict the prognosis of HCC. Studies indicate that elevated CHI3L1 levels correlate with poor survival rates, especially after curative resection. When combined with AFP, CHI3L1 significantly improves the diagnostic accuracy for HCC, offering clinicians a more reliable method for early detection and risk assessment. The integration of CHI3L1 measurements with routine clinical practice could transform patient management by enabling more precise risk stratification and tailored therapies.

The growing body of evidence supports the use of CHI3L1 not only as a biomarker for liver fibrosis but also as a potential therapeutic target. As a key regulator of fibrosis and inflammation, targeting CHI3L1 could mitigate disease progression and improve outcomes for patients suffering from chronic liver diseases. Further research into the molecular mechanisms underlying CHI3L1’s actions will enhance our understanding of liver pathology and pave the way for novel therapeutic strategies.

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Reference
Chao Tian, Shizhou Deng, Ming Yang, Baochen Bai, Lai Wei, Role of chitinase-3-like protein 1 in liver diseases: A comprehensive review, Genes & Diseases, Volume 12, Issue 6, 2025, 101653, https://doi.org/10.1016/j.gendis.2025.101653
Funding
National Key R & D Program of China 2022YFA1303804