title: Role of ITPA and IL28B variants in the management of chronic hepatitis C treatment.
abstract: The inosine triphosphatase (ITPA) gene and interleukin 28B (IL28-B) gene variants have been associated to protection of anemia and sustained virological response, respectively, in patients with chronic hepatitis C (CHC) during antiviral therapy. Aim of this study was to evaluate the single and combined role of both polymorphisms in the management of peg-interferon-ribavirin treatment in CHC patients. We studied 79 Italian patients with histology proven CHC treated with pegylated interferon plus ribavirin for 6-12 months on the base of HCV genotype. Patients were carefully followed-up for anemia development which was classified as mild, moderate or severe in relation to levels of haemoglobin decreasing; ribavirin dosage reduction and/or epoietin administration were carried out, where needed. Sustained virological response (SVR) was considered for HCV-RNA clearance after 6 months of treatment stop. Decay of haemoglobin at month 1 of treatment significantly correlated with ITPA activity (p 0.0004) and at multivariate analysis ITPA activity was the only parameter associate with anemia (R - 0.4; p 0.0004). SVR was obtained in 47% of patients. IL28B CC variant was associated with SVR (p 0.01), but IL28B polymorphisms had no influence on the ITPA polymorphism. This study confirms the role of ITPA variants in the prediction of development of severe anemia during antiviral treatment for CHC and demonstrates the absence of influence of IL28B variant on ITPA polymorphisms. These two polymorphisms can be useful in the management of patients that need antiviral therapy for HCV chronic infection.
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Zampino
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Alessio
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Marrone
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Stanzione
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Boemio
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Minichini
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Pisaturo
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Starace
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Luigi Elio
authors.initials: LE
authors.lastname: Adinolfi
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Evangelista
authors.initials: E
authors.lastname: Sagnelli
authors.affiliation: Department of Internal Medicine; Department of Mental Health and Public Medicine, Section of Infectious Diseases; Department of Clinical and Experimental Medicine and Surgery "F. Magrassi and A. Lanzara"; Department of Paediatrics, Second University of Naples, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coppola
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects; D007372:Interferons; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011755:Pyrophosphatases / Q000097:blood*; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D000095022:Interferon Lambda; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase; C428112:peginterferon beta-1a