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Prediction of Hepatocellular Carcinoma Development After Hepatitis C Virus Eradication Using Serum Wisteria Floribunda Agglutinin-Positive Mac-2-Binding Protein

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Prediction of Hepatocellular Carcinoma Development After Hepatitis C Virus Eradication Using Serum Wisteria Floribunda Agglutinin-Positive Mac-2-Binding Protein

Shunsuke Sato et al. Int J Mol Sci.

Abstract

We aimed to clarify the association between a novel serum fibrosis marker, Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA⁺-M2BP), and hepatocellular carcinoma (HCC) development in 355 patients with chronic hepatitis C who achieved sustained virologic response (SVR) through interferon-based antiviral therapy. Pretreatment serum WFA⁺-M2BP levels were quantified and the hazard ratios (HRs) for HCC development were retrospectively analyzed by Cox proportional hazard analysis. During the median follow-up time of 2.9 years, 12 patients developed HCC. Multivariate analysis demonstrated that high serum WFA⁺-M2BP (≥2.80 cut off index (COI), HR = 15.20, p = 0.013) and high fibrosis-4 (FIB-4) index (≥3.7, HR = 5.62, p = 0.034) were independent risk factors for HCC development. The three- and five-year cumulative incidence of HCC in patients with low WFA⁺-M2BP were 0.4% and 0.4%, respectively, whereas those of patients with high WFA⁺-M2BP were 7.7% and 17.6%, respectively (p < 0.001). In addition, combination of serum WFA⁺-M2BP and FIB-4 indices successfully stratified the risk of HCC: the five-year cumulative incidences of HCC were 26.9%, 6.8%, and 0.0% in patients with both, either, and none of these risk factors, respectively (p < 0.001). In conclusion, pretreatment serum WFA⁺-M2BP level is a useful predictor for HCC development after achieving SVR.

Keywords: WFA+-M2BP; chronic hepatitis C; hepatocellular carcinoma; risk factor; sustained virological response.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of serum Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) levels in the study cohort. COI, cut off index.
Figure 2
Figure 2
Relationships between Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) levels and patient characteristics at baseline. The Mann–Whitney U test or Kruskal–Wallis test was used for the categorical data. Spearman’s rank correlation coefficient was used for the continuous data. AFP, α-fetoprotein; ALT, alanine aminotransferase; BMI, body mass index; GGT, γ-glutamyl transpeptidase; HCV, hepatitis C virus.
Figure 3
Figure 3
Cumulative incidence of hepatocellular carcinoma (HCC) development after sustained virologic response, shown according to serum Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) level (a) or fibrosis-4 (FIB-4) index (b).
Figure 4
Figure 4
(a) Relationship between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) levels and Fibrosis-4 (FIB-4) index. Black and gray circles represent patients with and without HCC development, respectively. Vertical and horizontal line represent FIB-4 index = 3.7 and WFA+-M2BP = 2.80 COI, respectively; (b) Cumulative incidence of hepatocellular carcinoma (HCC) development after sustained virologic response, shown according to serum WFA+-M2BP level and FIB-4 index.
Figure 5
Figure 5
Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) level and Fibrosis-4 (FIB-4) index in each fibrosis stage. n = 333.

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