title: Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis.
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.
authors.affiliation: Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: de la Fuente
authors.affiliation: Servicio de Medicina Interna, Instituto de Investigación Sanitaria del Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. mariajesus.citores@salud.madrid.org.
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Citores
authors.affiliation: Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Duca
authors.affiliation: Grupo de Inmunogenética e Histocompatibilidad, Servicio de Inmunología, Instituto de Investigación Sanitaria del Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cisneros
authors.affiliation: Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Isolina
authors.initials: I
authors.lastname: Baños
authors.affiliation: Grupo de Inmunogenética e Histocompatibilidad, Servicio de Inmunología, Instituto de Investigación Sanitaria del Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vilches
authors.affiliation: Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.|Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Valentín
authors.initials: V
authors.lastname: Cuervas-Mons
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Gene polymorphism; Hepatocellular carcinoma; Interleukin-28B; Liver cirrhosis; rs12979860