Validation of a glycomics-based test associated with risk of HCC development in cirrhosis

Background Cirrhosis is the main risk factor for the development of Hepatocellular carcinoma (HCC). Six-monthly screening with ultrasound is advocated for the surveillance of cirrhotic patients. We recently showed that a glycomics-based test (GlycoCirrhoTest [GCT]) can provide additional information regarding the risk of HCC development in cirrhotic patients. Aims Independent clinical validation of the GCT for the assessment of the risk of HCC development in cirrhosis and exploration of additional clinical parameters to assess HCC risk. Methods Validation study on serum samples of patients with established compensated cirrhosis (CHILD Pugh A & B) in a tertiary liver centre. Serum N-glycan profiling was performed and GCT was calculated at baseline. During the follow up period, patients were screened for the presence of HCC every 6 months with ultrasound. Results A total of 198 cirrhotic patients were followed in clinical routine for the development of HCC. 29 patients developed HCC and one died during follow up. At baseline, the mean GCT value was significantly higher in patients who developed HCC within 3 years compared to patients who did not develop HCC (Welch’s t-test, p-value 3 years: 0.034). A high GCT at baseline was associated with increased HCC incidence with a HR of 5.8 (95% CI: 0.7 – 48), 4.8 (95% CI: 1.4 – 16) and 3.6 (95% CI: 1.2 – 11) at 3, 5 and 7 years post sampling respectively. Results from this study are in agreement with previous results 1 , as shown in a meta-analysis. Moreover, we also identified albumin as an independent predictor for developing HCC in a multivariate analysis revealing that low albumin blood levels (< 4g/dL) are also associated with increased HCC incidence with a HR at 7 years of 2.3 (95% CI: 1.1 - 4.9). For subjects with both high GCT and low albumin we found a HR of 9.8 (95% CI: 3.5 to 27) at 7 years. Conclusions GCT is a glycomics-based test that provides additional information for risk assessment of HCC development in cirrhosis. This information could be used to develop personalised HCC screening programs in cirrhotic patients according to the value of GCT. Serum albumin levels could provide additional and GCT-independent information which may add to the utility of the test.