Circulating Interleukin-37 as a Biomarker Candidate for Hepatocellular Carcinoma in Decompensated Advanced Chronic Liver Disease.

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.