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Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis

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Abstract

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n = 202) or alcoholic cirrhosis (n = 109). HCV patients were older (p = 0.012) and less likely males (p < 0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95 % CI 2.11–17.53; p < 0.001] and T allele carriage (CT + TT; OR 2.3, CI 95 % 1.42–3.72; p = 0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT + TT; OR 1.79, CI 95 % 1.03–3.09; p = 0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95 % 1.5–4.7; p < 0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p = 0.84) and alcoholic patients (p = 0.91). Multivariate analysis showed that older age (OR 1.06, CI 95 % 1.02–1.1; p = 0.003) and male gender (OR 2.49, CI 95 % 1.24–5; p = 0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.

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Abbreviations

ALC:

Alcoholic

CI:

Confidential interval

CTP:

Child–Turcotte–Pugh

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

IFN-λ:

Interferon-λ

IL28B:

Interleukin-28B

LT:

Liver transplantation

OR:

Odds ratio

PCR:

Polymerase chain reaction

SOT:

Solid organ transplantation

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Acknowledgments

This work was partially supported by Instituto de Salud Carlos III (PI08/1561) and Cátedra Universidad Autónoma de Madrid-Fundación Lair.

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    Authors and Affiliations

    1. Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain

      Sara de la Fuente

    2. Servicio de Medicina Interna, Instituto de Investigación Sanitaria del Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain

      María-Jesús Citores

    3. Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain

      Ana Duca, Isolina Baños & Valentín Cuervas-Mons

    4. Grupo de Inmunogenética e Histocompatibilidad, Servicio de Inmunología, Instituto de Investigación Sanitaria del Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain

      Elisa Cisneros & Carlos Vilches

    5. Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

      Valentín Cuervas-Mons

    Authors
    1. Sara de la Fuente
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    Correspondence to María-Jesús Citores.

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    The authors declare that they have no conflict of interest.

    Ethical approval

    All procedures followed were in accordance with the ethical standards of the Puerta de Hierro University Hospital and with the Helsinki Declaration of 1975, as revised in 2008. Ethical approval was obtained from the Institutional Review Board for Human Research [Research Ethics Committee (REC)] at Puerta de Hierro University Hospital (Madrid, Spain) (REC June 27, 2011).

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    Informed consent was obtained from all patients.

    Additional information

    Sara de la Fuente and María-Jesús Citores have contributed equally to this study.

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    de la Fuente, S., Citores, MJ., Duca, A. et al. Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis. Clin Exp Med 17, 217–223 (2017). https://doi.org/10.1007/s10238-016-0418-1

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    • DOI: https://doi.org/10.1007/s10238-016-0418-1

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