Serum Mac‐2‐binding protein glycosylation isomer and risk of hepatocellular carcinoma in entecavir‐treated chronic hepatitis B patients

Abstract

Background and Aim Hepatocellular carcinoma (HCC) can still develop in chronic hepatitis B (CHB) patients receiving antiviral treatment. Serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis. We investigated its role on incidence of HCC in entecavir (ETV)‐treated CHB patients. Methods We identified HCC cases diagnosed at ≥ 1 year of ETV treatment. CHB patients without HCC (matched for age, gender, baseline hepatitis B virus‐DNA, and duration of ETV treatment) were identified in approximately 1:2 ratio (HCC: non‐HCC) for comparison. Serum samples were retrieved at baseline (initiation of ETV), 3, and 5 years of ETV for serum M2BPGi measurement (expressed in cut‐off index [COI]). Results One hundred HCC cases were matched with 185 CHB patients without HCC (median age 56.7 years, 78.9% male, baseline hepatitis B virus‐DNA 5.6 logIU/mL, and median follow‐up 7.1 years). Median time from ETV initiation to incident HCC was 3.9 years. Serum M2BPGi levels were significantly higher in HCC cases compared with controls at baseline and year 3 (1.25 vs 0.98 [P = 0.004], 0.89 vs 0.74 [P = 0.018] COI, respectively). Multivariate analysis showed that baseline M2BPGi was the only independent factor associated with incident HCC (odds ratio 1.241, 95% confidence interval 1.039–1.482, P = 0.017). Using a cut‐off value of 1.15 COI, the sensitivity, specificity, positive predictive value, and negative predictive value of baseline serum M2BPGi in cirrhotic patients to predict incident HCC were 90%, 53.8%, 69.6%, and 82.1%, respectively. Conclusions Baseline and 3‐year serum M2BPGi may be useful to identify high risk patients on antiviral treatment for subsequent HCC development.

Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases

“…When the presence or absence of HCC was evaluated after the fibrosis stages were adjusted, no difference in M2BPGi levels was found [58], which was considered to reflect its carcinogenic potential due to fibrosis progression. Longitudinal observational studies have reported that patients with M2BPGi level ≥ 0.71−2.0 have a high risk of HCC development (Table 2) [53,58,[62][63][64][65][66][67][68][69]. In considering the risk of carcinogenesis, the presence or absence of treatment should be considered.…”

Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

“…M2BPGi has been used as a liver fibrosis marker for various liver diseases [65], including NAFLD [43,64,66]. Accumulating evidence suggests that higher levels of serum M2BPGi can predict HCC incidence in patients with chronic hepatitis B [67][68][69][70][71][72]. According to a report by Kawanaka et al [73], the carcinogenic rate was as high as 6.8% at 5 years and 21.1% at 10 years in NAFLD cases where M2BPGi was 1.26 or higher, while the rate was as low as 1.7% at 5 years and 1.7% at 10 years in patients with M2BPGi below 1.26 [73].…”

Dynamic evaluation of hepatocellular carcinoma prediction models in patients with chronic hepatitis B receiving nucleotide/nucleoside analogue treatment

“…Therefore, undetectable HBV DNA may be used as a factor constituting a predictive model for HCC development. Furthermore, previous reports showed that HBsAg, [20][21][22] HBcrAg, [21][22][23] HBV DNA level, 19,24 liver stiffness 25 and M2BPGi [26][27][28][29][30] during treatment were useful for stratification of carcinogenic risk. Future studies are required to determine whether a more accurate carcinogenic risk prediction model could be constructed by combining these scores with PAGE-B.…”