Hepatocellular carcinoma diagnosis using a novel electrochemiluminescence immunoassay targeting serum IgM-free AIM

Clin J Gastroenterol. 2022 Feb;15(1):41-51. doi: 10.1007/s12328-021-01567-4. Epub 2022 Jan 4.


Background: Recent increases in the number of patients with non-alcoholic steatohepatitis (NASH) warrant the identification of biomarkers for early detection of hepatocellular carcinoma (HCC) associated with NASH (NASH-HCC). IgM-free apoptosis inhibitor of macrophage (AIM), which generally associates with IgM in blood and exerts its biological function by dissociation from IgM, may serve as an effective biomarker for NASH-HCC. Here, we established a fully automatic and high-throughput electrochemiluminescence immunoassay (ECLIA) to measure IgM-free AIM and investigated its efficacy in diagnosing NASH-HCC and viral HCC.

Methods: IgM-free AIM levels were measured in 212 serum samples from patients with, or without, HCC related to NASH, hepatitis B virus, and hepatitis C virus, using ECLIA. We also developed an ECLIA for measuring both IgM-free and IgM-bound AIM and investigated the existing form of AIM in blood by size-exclusion chromatography.

Results: IgM-free AIM levels were significantly higher in the HCC group than in the non-HCC group, regardless of the associated pathogenesis. Moreover, the area under the receiver operating curve for IgM-free AIM was greater than that for conventional HCC biomarkers, alpha-fetoprotein or des-γ-carboxy prothrombin, regardless of the cancer stage. ECLIA counts of IgM-free AIM derived from samples fractionated by size-exclusion chromatography were significantly higher in patients with NASH-HCC than in healthy volunteers and in patients with non-alcoholic fatty liver and NASH.

Conclusions: Serum IgM-free AIM may represent a universal HCC diagnostic marker superior to alpha-fetoprotein or des-γ-carboxy prothrombin. Our newly established ECLIA could contribute to further clinical studies on AIM and in vitro HCC diagnosis.

Keywords: Diagnosis; Electrochemiluminescence immunoassay; Hepatocellular carcinoma; IgM-free apoptosis inhibitor of macrophage; Non-alcoholic steatohepatitis.

MeSH terms

  • Apoptosis Regulatory Proteins / blood*
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular* / pathology
  • Humans
  • Immunoassay / methods
  • Liver Neoplasms* / pathology
  • Macrophages / pathology
  • Non-alcoholic Fatty Liver Disease* / complications
  • Prothrombin
  • Receptors, Scavenger / blood*
  • alpha-Fetoproteins


  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • CD5L protein, human
  • Receptors, Scavenger
  • alpha-Fetoproteins
  • Prothrombin