Association of Mannose-Binding-Lectin-2-gene Polymorphism to the Development of Hepatitis-C-induced Hepatocellular Carcinoma

Background:

Development of end-stage liver and graft disease is suspected to be partially determined by individual genetic background. Mannose-binding lectin-2 (MBL-2) is an important immunomodullatory factor, which is supposed to be involved in complement activation and oncogenesis. Genetic polymorphisms of MBL-2 alter the protein functionality. Aim of our study was to determine the prevalence of MBL-2-polymorphism (rs7096206) in HCV-induced hepatocellular carcinoma (HCC) based on histological analysis of explanted livers in patients undergoing liver transplantation.

Methods:

177 patients, who underwent liver transplantation for HCV-induced liver disease, were genotyped for MBL-2 by TaqMan genotyping assay. 62 patients with histologically confirmed HCC were compared to 115 patients without HCC. Growth patern, HCC-size, multilocularity and pre-transplant AFP-level were compared among the genotype groups.

Results:

The prevalence of GG and GC- genotypes was significantly higher among patients with HCC compared to tumour-free explanted livers (p=0.004; OR 2.5; 1.3–4.8). MBL-2-polymorphisms was significantly associated to the size of HCC (p=0.022), pre-transplant AFP-level (p=0.003), AFP-negativity (p=0.002) and bilobar growth (p=0.038). Conclusion: MBL-2-polymorphism seems to be involved in the development of pre-transplant HCV-induced HCC and might be a useful genetic risk factor for tumor development in patients with hepatitis-C.

Fig.1: HCC und MBL-2-genotype groups

Fig.2: Categorized pre-transplant AFP-levels among MBL-2-genotypes

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HCC - HCV - Mbl-2 - genetic variants - liver transplantation