Impact of immunogenetic IL28B polymorphism on natural outcome of HCV infection.
With the aim of investigating whether interleukin 28B gene (IL28B) rs1297860 polymorphism is associated with different hepatitis C (HCV) infection statuses, we compared IL28B allelic distribution in an Italian case series of 1050 patients with chronic infection and different outcomes, 47 individuals who spontaneously cleared HCV, and 178 blood donors. Furthermore, we compared IL28B variants among 3882 Caucasian patients with chronic infection, 397 with spontaneous clearance, and 1366 blood donors reported in PubMed. Overall data confirmed a relation between IL28B C allele and HCV spontaneous clearance. Furthermore, we found that IL28B T allele had a weak relation with chronic HCV progression to hepatocellular carcinoma. Study findings are in accordance with the hepatocellular carcinogenic model where IL28B TT genotype, by promoting a persistent chronic hepatitis which leads to both hepatocyte injury and chronic inflammation, could facilitate HCC development. Conversely, patients with lymphoproliferative disorders had not any significantly different IL28B rs1297860 allelic distribution than those with chronic HCV, but, like all chronic HCV-related diseases, they showed a lower CC frequency than patients who spontaneously cleared HCV. Study results confirmed the model of persistent HCV infection as a risk factor for the pathogenesis of both liver and lymphoproliferative disorders.
Bio-Proteomics Facility, Department of Translational Research, CRO, National Cancer Institute, 33081 Aviano, Italy.
Valli
V
De Re
Interdepartmental Center for Systemic Manifestations of Hepatitis Virus MASVE, Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.
Laura
L
Gragnani
Interdepartmental Center for Systemic Manifestations of Hepatitis Virus MASVE, Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.
Elisa
0000-0001-8856-6006
E
Fognani
Interdepartmental Center for Systemic Manifestations of Hepatitis Virus MASVE, Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.
Alessia
A
Piluso
Hepatobiliary Unit, National Cancer Institute "Fondazione Pascale", 80138 Naples, Italy.
Francesco
F
Izzo
Liver Unit, IRCCS Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo, Italy.
Alessandra
A
Mangia
Cytogenetics and Molecular Biology Unit, Santa Maria degli Angeli Hospital Pordenone, 33170 Pordenone, Italy.
Marina
M
Crovatto
Cytogenetics and Molecular Biology Unit, Santa Maria degli Angeli Hospital Pordenone, 33170 Pordenone, Italy.
Graziella
G
Gava
Internal Medicine-Liver Unit, Santa Maria degli Angeli Hospital Pordenone, 33170 Pordenone, Italy.
Pietro
P
Casarin
Immunology Section, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, 70121 Bari, Italy.
Domenico
D
Sansonno
Immunology Section, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, 70121 Bari, Italy.
Vito
V
Racanelli
Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital Santa Maria della Misericordia, 33100 Udine, Italy.
Salvatore
S
De Vita
Hematology and Transplant Unit, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
Pietro
P
Pioltelli
Bio-Proteomics Facility, Department of Translational Research, CRO, National Cancer Institute, 33081 Aviano, Italy.
Laura
L
Caggiari
Bio-Proteomics Facility, Department of Translational Research, CRO, National Cancer Institute, 33081 Aviano, Italy.
Mariangela
M
De Zorzi
Medical Oncology, Centro di Riferimento Oncologico, 33081 Aviano, Pordenone, Italy.
Massimiliano
M
Berretta
Epidemiology and Biostatistics, Centro di Riferimento Oncologico, IRCCS, 33081 Aviano, Italy.
Andrea
0000-0002-7696-0580
A
Gini
Epidemiology and Biostatistics, Centro di Riferimento Oncologico, IRCCS, 33081 Aviano, Italy.
Antonella
A
Zucchetto
Molecular Biology and Viral Oncology, National Cancer Institute "Fondazione Pascale", 80138 Naples, Italy.
Franco Maria
FM
Buonaguro
Bio-Proteomics Facility, Department of Translational Research, CRO, National Cancer Institute, 33081 Aviano, Italy.
Paolo
0000-0002-9502-1781
P
De Paoli
Interdepartmental Center for Systemic Manifestations of Hepatitis Virus MASVE, Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.
Anna Linda
AL
Zignego
D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics / Q000473:pathology; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007125:Immunogenetics; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda