title: PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study.
abstract: OBJECTIVE
  Dual PEGylated interferon-α (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population.
  
  
  METHODS
  Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors.
  
  
  RESULTS
  IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNFα (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3.
  
  
  CONCLUSIONS
  IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.
authors: Servicio de Farmacia del Hospital General Universitario de Valencia.. xmilara@hotmail.com.
authors: Javier
authors: J
authors: Milara
authors: Servicio de Farmacia Complejo Hospitalario Universitario A Coruña.. xmilara@hotmail.com.
authors: Maria
authors: M
authors: Outeda-Macias
authors: Hospital Reina Sofía de Córdoba.. xmilara@hotmail.com.
authors: M Dolores
authors: MD
authors: Aumente-Rubio
authors: Hospital General del SVS de Alicante.. xmilara@hotmail.com.
authors: Patricio
authors: P
authors: Más-Serrano
authors: Clínica Universitaria de Navarra.. xmilara@hotmail.com.
authors: Azucena
authors: A
authors: Aldaz
authors: Hospital Clínico Universitario de Salamanca.. xmilara@hotmail.com.
authors: M Victoria
authors: MV
authors: Calvo
authors: Servicio de Farmacia Hospital General Universitario Santa Lucía, Cartagena.. xmilara@hotmail.com.
authors: M Sergia
authors: MS
authors: García-Simón
authors: Hospital Gregorio Marañon. Madrid.. xmilara@hotmail.com.
authors: Marisa
authors: M
authors: Martin-Barbero
authors: Hospital Universitari Bellvitge. IDIBELL.. xmilara@hotmail.com.
authors: Núria
authors: N
authors: Padullés-Zamora
authors: Hospital Universitario Arnau de Vilanova. Lleida.. xmilara@hotmail.com.
authors: Juan Antonio
authors: JA
authors: Schoenenberger
authors: Complejo Hospitalario Universitario INSULAR Materno-Infantil. Las Palmas de Gran Canaria.. xmilara@hotmail.com.
authors: Marianne
authors: M
authors: Saavedra-Aldrich
authors: Hospital Universitario Nuestra Señora de Candelaria. Tenerife. España.. xmilara@hotmail.com.
authors: Enrique
authors: E
authors: Tévar-Alfonso
authors: Servicio de Farmacia del Hospital General Universitario de Valencia.. xmilara@hotmail.com.
authors: Ana
authors: A
authors: Saval
authors: Servicio de Farmacia del Hospital General Universitario de Valencia.. xmilara@hotmail.com.
authors: Alfonso
authors: A
authors: Pastor-Clerigues
authors: Servicio de Farmacia del Hospital General Universitario de Valencia.. xmilara@hotmail.com.
authors: Marta
authors: M
authors: García
authors: Servicio de Farmacia Complejo Hospitalario Universitario A Coruña.. xmilara@hotmail.com.
authors: Luis
authors: L
authors: Margusino-Framiñan
authors: Hospital Reina Sofía de Córdoba.. xmilara@hotmail.com.
authors: Jose Luis
authors: JL
authors: Montero-Alvarez
authors: Hospital General del SVS de Alicante.. xmilara@hotmail.com.
authors: Esperanza
authors: E
authors: Merino
authors: Clínica Universitaria de Navarra.. xmilara@hotmail.com.
authors: Jose Ignacio
authors: JI
authors: Herrero
authors: Hospital Clínico Universitario de Salamanca.. xmilara@hotmail.com.
authors: Mónica
authors: M
authors: Beunza
authors: Servicio de Farmacia Hospital General Universitario Santa Lucía, Cartagena.. xmilara@hotmail.com.
authors: Pablo
authors: P
authors: Conesa-Zamora
authors: Hospital Gregorio Marañon. Madrid.. xmilara@hotmail.com.
authors: Alvaro
authors: A
authors: Gimenez-Manzorro
authors: Hospital Universitari Bellvitge. IDIBELL.. xmilara@hotmail.com.
authors: Dolors
authors: D
authors: Comas-Sugrañes
authors: Hospital Universitario Arnau de Vilanova. Lleida.. xmilara@hotmail.com.
authors: Manuel
authors: M
authors: Cano-Marron
authors: Complejo Hospitalario Universitario INSULAR Materno-Infantil. Las Palmas de Gran Canaria.. xmilara@hotmail.com.
authors: Elena
authors: E
authors: Jiménez-Mutiloa
authors: Hospital Universitario Nuestra Señora de Candelaria. Tenerife. España.. xmilara@hotmail.com.
authors: Pilar
authors: P
authors: Díaz-Ruíz
authors: Servicio de Farmacia del Hospital General Universitario de Valencia.. xmilara@hotmail.com.
authors: Julio
authors: J
authors: Cortijo
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011092:Polyethylene Glycols; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D013030:Spain; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D012254:Ribavirin