Code XG003.P


ELISA Kit for the detection of Squamous Cell Carcinoma Antigen variants Immune Complexes (SCCA-IgM)

Hepa-IC is an innovative in-vitro diagnostic method for the detection of Squamous Cell Carcinoma Antigen (SCCA) variants in the form of circulating immunocomplexes (SCCA-IgM). Hepa-IC is a highly specific and sensitive ELISA kit for liver disease detection, designed to measure SCCA-IgM in patients’ serum. The serological levels of the biomarker are expressed as Arbitrary Units (AU)/milliliter (mL), using a calibrator as reference. Many clinical studies have been performed to validate SCCA-IgM and evaluate its clinical potential.

Companion diagnostic to identify hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV) infection treated with the new direct-acting anti-virals (DAAs) [Ricco G, et al. Hepatology 2017. In press.]
HCV-infected patients with cirrhosis who are treated with DAAs continue to be at high risk of HCC development, even after successful viral eradication; serological levels of SCCA-IgM can help identifying the patients who will develop HCC in the first 18 months after DAAs therapy.

Detection of hepatocellular carcinoma (HCC) [Beneduce L, et al. Cancer. 2005]
Early diagnosis of HCC is difficult due to the lack of adequate biomarkers that clearly differentiate HCC from benign liver lesion. Table 1 shows the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of SCCA-IgM at the cut-off value of 120 AU/mL for detecting HCC compared to healthy controls and patients with cirrhosis or chronic hepatitis.

Table 1: Sensitivity, specificity, PPV and NPV of SCCA-IgM.
SCCA-IgM >120 AU/mLSensitivity (%)Specificity (%)PPV (%)NPV (%)
HCC vs. Control7010010077
HCC vs. Cirrhosis70747371
HCC vs. Chronic Hep70828073

Surveillance of cirrhotic patients [Buccione D, et al. OJGas. 2012]
Multicenter, retrospective, longitudinal studies on patients with HCV- related cirrhosis monitored for 12-72 months have demonstrated that the use of Hepa-IC kit may detect patients with cirrhosis at lower risk of developing HCC. Patients with HCV-related cirrhosis who did not develop HCC after at least 12 months of follow-up had SCCA-IgM serological levels persistently below 300 AU/mL. On the other hand, patients with HCV-related cirrhosis at higher risk of HCC development showed SCCA-IgM levels above 525 AU/mL.

Monitoring the progression of cirrhotic patients to HCC [Pontisso P, et al. Int J Cancer. 2006]
The progressive increase of SCCA-IgM over time in cirrhotic patients is significantly associated with tumor progression. Longitudinal studies during a median follow up of 4 years show that the increase over time of SCCA-IgM is significantly higher in the cirrhotic patients who developed HCC compared to those who did not.

Monitoring the progression of liver disease in patients with chronic hepatitis [Biasiolo A, et al. J Viral Hepat. 2008]
A significant increase of SCCA-IgM during follow up can be detected in patients with progressive disease, but not in those without histological deterioration. Monitoring SCCA-IgM over time could be a useful approach to predict disease outcome in individual patients with chronic hepatitis.

Monitoring anti-viral treatment response in patients with chronic hepatitis [Giannini EG, et al. J Viral Hepat. 2010]
Serological levels of SCCA-IgM decreases significantly over time at 12-month follow up in patients with sustained virological response, whereas null responders show stable levels of SCCA-IgM at the end of treatment and during follow-up. Based on this, SCCA-IgM may be used in the clinical practice to predict the therapeutic outcome of antiviral treatment with PEG-IFN and ribavirin in cirrhotic patients with HCV infection.

Prognosis of HCC patients [Pozzan C, et al. J Gastroenterol Hepatol. 2014]
With a cut-off value of 130 AU/mL, SCCA-IgM was efficient at identifying patients with longer survival and predicting progression-free survival.

Identification of non-alcoholic steatohepatitis (NASH) in HCV-positive patients [Martini A, et al. J Viral Hepat. 2015]
Patients with histological NASH show elevated levels of SCCA-IgM; moreover, the biomarker, similarly to HCV genotype 3, was found independently associated with NASH at multivariate analysis.

Table 2: SCCA-IgM levels interpretation
SCCA-IgM Chronic Hepatitis Cirrhosis
>500* AU/mL Severe liver disease, with high probability of HCC development. Intensify surveillance with US (every 4 or 6 months) to detect early cancer nodules High risk of HCC development
Repeat US every 4 months and/or use other imaging techniques (CT/MRI)
200-500* AU/mL Repeat SCCA-IgM analysis (after 6 or 12 months)
Increase = evolution to more severe stages;
Decrease after treatment = successful therapy;
No change = stable disease.
Medium risk of HCC.
Repeat SCCA-IgM analysis every 6 months. The persistent increase over time of SCCA-IgM is associated with high risk of HCC development
<200* AU/mL Low probability of active liver disease Low risk of HCC
Surveillance as suggested by guidelines (US every 6 months)
* Standard values of references