Abstract
This study examines the role of M2BPGi, a novel seromarker for chronic hepatitis, in predicting hepatocellular carcinoma (HCC) among untreated chronic hepatitis B (CHB) patients. In this nested case-control study, 1070 samples were assayed for M2BPGi, including 357 samples from HCC cases, and 713 samples from non-HCC controls, collected at various times throughout follow-up. HCC case samples were stratified according to years prior to diagnosis. Associations between M2BPGi and HCC were examined with multivariate logistic regression. M2BPGi, α-fetoprotein (AFP), and hepatitis B surface antigen (HBsAg) levels were significant independent short-term predictors of HCC, while M2BPGi was insignificant in long-term analyses. Compared to M2BPGi levels <1.0 cut-off index (COI), those with levels ≥2.0 COI had multivariate odds ratios (95% CI) for HCC of 7.40 (2.40–22.78), 6.46 (2.58–16.18), and 2.24 (0.97–5.15), respectively, for prediction of HCC within 1-2, 2–5, and ≥5 years. Higher proportions of individuals had M2BPGi levels ≥2.0 COI in samples closer to HCC diagnosis. Areas under receiver operating characteristic curves for models with M2BPGi, AFP, and HBsAg levels predicting HCC within 1–2, 2–5, and >5 years were 0.84, 0.81, and 0.75. M2BPGi is a strong and independent short-term predictor of HCC in CHB patients.
Highlights
In searching for precursors of hepatocellular carcinoma (HCC) development, tracking of liver fibrosis progression and the degree of necroinflammation present are important for determining the severity of liver disease[5,6,17]
The current study aims to examine the role of M2BPGi as a predictor of HCC in a time-dependent manner among a community-based cohort of untreated individuals infected with chronic hepatitis B
To investigate time trends of M2BPGi, we examined M2BPGi levels at different time intervals prior to HCC (Fig. 2a)
Summary
In searching for precursors of HCC development, tracking of liver fibrosis progression and the degree of necroinflammation present are important for determining the severity of liver disease[5,6,17]. Recent studies have since reported Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA + -M2BP) to be a more accurate surrogate glycobiomarker for assessing liver fibrosis in hospital-based treated patients[20]. This marker was later abbreviated to M2BPGi (M2BP glycosylation isomer). In studies of patients with CHB and chronic hepatitis C (HCV), M2BPGi was able to accurately distinguish between stages of fibrosis, with higher levels representing more severe stages of fibrosis[21,22,23,24,25,26]. M2BPGi levels have been shown to distinguish stages of fibrosis among Non-alcoholic fatty liver disease (NAFLD) patients[27]. The current study aims to examine the role of M2BPGi as a predictor of HCC in a time-dependent manner among a community-based cohort of untreated individuals infected with chronic hepatitis B
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