Related Experiment Video
Updated: May 5, 2026
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Circulating Interleukin-37 as a Biomarker Candidate for Hepatocellular Carcinoma in Decompensated Advanced Chronic
Michael Mederer1, Johanna Piater1, Felix Keller2
1Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Insights
Interleukin-37 (IL-37) may serve as a novel biomarker for detecting hepatocellular carcinoma (HCC) in advanced chronic liver disease (ACLD). Lower IL-37 levels in decompensated cirrhosis patients indicate potential HCC presence, complementing alpha-fetoprotein (AFP).
Area of Science:
- Hepatology
- Oncology
- Immunology
Background:
- Hepatocellular carcinoma (HCC) is a major cause of mortality in advanced chronic liver disease (ACLD).
- Traditional biomarkers like alpha-fetoprotein (AFP) have limitations in detecting HCC, especially in decompensated cirrhosis.
- Interleukin-37 (IL-37), an anti-inflammatory cytokine, shows potential as a biomarker in hepatocarcinogenesis.
Purpose of the Study:
- To investigate serum IL-37 concentrations as a potential biomarker for HCC in patients with ACLD.
- To compare IL-37 levels in patients with and without HCC across different stages of liver disease severity.
- To assess the relationship between IL-37, AFP, and patient survival in ACLD.
Main Methods:
- Prospective study of 221 ACLD patients (54 with HCC, 167 without).
- Serum IL-37 levels measured at clinical assessment.
- Routine laboratory parameters, disease severity scores (MELD, Child-Pugh), and tumor staging (BCLC, LI-RADS) were recorded.
Main Results:
- IL-37 levels did not differ significantly between compensated ACLD patients with or without HCC.
- In decompensated ACLD, IL-37 concentrations were significantly lower in patients with HCC, especially with advanced hepatic dysfunction.
- IL-37 showed a potential inverse relationship with AFP in compensated ACLD and appeared more informative in decompensated ACLD.
Conclusions:
- IL-37 is a promising biomarker candidate reflecting immune regulation and tumor biology in ACLD.
- IL-37 may complement AFP for HCC detection in decompensated cirrhosis, where AFP is less reliable.
- Further large-scale longitudinal studies are needed to validate IL-37 as a predictive and prognostic marker in high-risk populations.
Abstract:
Hepatocellular carcinoma (HCC) remains a leading cause of mortality in patients with advanced chronic liver disease (ACLD), particularly in those with decompensated cirrhosis, where traditional biomarkers such as alpha-fetoprotein (AFP) often fail to reliably detect malignancy. Interleukin-37 (IL-37), an anti-inflammatory cytokine with reported tumour-suppressive properties, has emerged as a candidate biomarker in hepatocarcinogenesis. This prospective study investigated serum IL-37 concentrations in 221 patients with ACLD (54 with HCC and 167 without HCC). IL-37 was measured at the time of clinical assessment, and routine laboratory parameters, disease severity scores (MELD, Child-Pugh), and tumour staging (BCLC, LI-RADS) were recorded. IL-37 levels were not significantly different in patients with compensated ACLD (cACLD) with or without HCC. In contrast, in decompensated ACLD (dACLD), IL-37 concentrations were significantly lower in patients with HCC, particularly in those with advanced hepatic dysfunction. Stratified analyses revealed an inverse relationship between IL-37 and AFP in cACLD, whereas in dACLD, IL-37 appeared more informative, as AFP levels were affected by systemic inflammation. Patients with prevalent HCC exhibited numerically lower IL-37 compared with those who developed HCC during follow-up, suggesting that IL-37 decline may precede overt tumour manifestation. Kaplan-Meier survival analysis showed a trend toward improved overall survival in patients with higher IL-37 levels, although this did not reach statistical significance. These findings highlight IL-37 as a promising biomarker candidate that might reflect immune regulation and tumour biology in ACLD. In particular, IL-37 may complement AFP for HCC detection in decompensated cirrhosis, where conventional biomarkers often fail. Future studies with larger, longitudinal cohorts are warranted to validate IL-37 as a predictive and prognostic marker in high-risk populations.
