A Mac-2 Binding Protein Glycosylation Isomer-Based Risk Model Predicts Hepatocellular Carcinoma in HBV-Related Cirrhotic Patients on Antiviral Therapy

Abstract

Mac-2 binding protein glycosylation isomer (M2BPGi) has not been used in a risk score to predict hepatocellular carcinoma (HCC). We enrolled 1003 patients with chronic hepatitis B and cirrhosis receiving entecavir or tenofovir therapy for more than12 months to construct an HCC risk score. In the development cohort, Cox regression analysis identified male gender, age, platelet count, AFP and M2BPGi levels at 12 months of treatment as independent risk factors of HCC. We developed the HCC risk prediction model, the ASPAM-B score, based on age, sex, platelet count, AFP and M2BPGi levels at 12 months of treatment, with the total scores ranging from 0 to 11.5. This risk model accurately classified patients into low (0–3.5), medium (4–7), and high (>7) risk in the development and validation groups (p < 0.001). The areas under the receiver operating characteristic curve (AUROC) of 3-, 5- and 9-year risks of HCC were 0.742, 0.728 and 0.719, respectively, in the development cohort. All AUROC between the ASPAM-B and APA-B, PAGE-B, RWS-HCC and THRI scores at 3–9 years were significantly different. The M2BPGi-based risk model exhibited good discriminant function in predicting HCC in cirrhotic patients who received long-term antiviral treatment.

Mac-2 binding protein glycosylation isomer at 5 years of antiviral therapy predict hepatocellular carcinoma and mortality beyond year 5 in chronic hepatitis B patients with cirrhosis

“…The M2BPGi level measured at year 5 was a better predictor than at the baseline or one year of treatment. This is in line with our previous studies demonstrating that M2BPGi levels at 12 months of treatment predict liver-related mortality in patients with cirrhosis receiving longterm NA treatment [12] and can be accounted for by the notion that M2BPGi may reflect the severity of cirrhosis or hepatocyte dysfunction [27].…”

“…AUROCs were calculated by time-dependent ROC curves for assessing the performance of the risk models and C-statistic was used to assess the overall performance of the risk model. AUROCs were used to evaluate the performance of the AMA, ASPAM-B and PAGE-B scores [12,18]. The time-dependent receiveroperating characteristic (ROC) curve was analyzed to determine the best cutoff values for AFP and M2BPGi at initial or 5 years of treatment [19].…”

“…We compared the AUROCs among AMA, ASPAM-B and PAGE-B using our data at 5 years of treatment [12,16].…”

“…The Wisteria floribunda agglutinin (WFA)positive Mac-2 binding protein glycosylation isomer (M2BPGi) can induce the expression of Mac-2 protein in Kupffer cells [11]. Our recent study showed that M2BPGi level at 12 months of treatment was a useful marker for predicting HCC development in cirrhotic patients receiving long-term NA treatment [12]. It remains unclear whether M2BPGi level at 5 years of treatment could predict HCC beyond year 5 of NA therapy.…”