title: Liver fibrosis, host genetic and hepatitis C virus related parameters as predictive factors of response to therapy against hepatitis C virus in HIV/HCV coinfected patients.
abstract: OBJECTIVE
  To establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism).
  
  
  METHODS
  A sample of 267 HIV/HCV coinfected patients was treated with Peg-IFN and RBV. Predictive factors of rapid (RVR) and sustained (SVR) virological response were analyzed. Independent variables were age, sex, IL28B, -238 TNF-α and -592 IL-10 polymorphisms, HCV genotype, HCV-RNA levels, significant fibrosis or cirrhosis and CD4+ T cell count.
  
  
  RESULTS
  Patients infected by HCV genotype 1 (n = 187) showed RVR and SVR in 12% and 39% of cases, respectively. The parameters associated with RVR were IL28B genotype CC and plasma HCV-RNA levels <600,000 IU/ml. Advanced liver fibrosis was negatively associated with SVR in patients without RVR. A SVR was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were IL28B genotype CC and an HCV-RNA <600,000 IU/ml. A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis. TNF-α and IL-10 polymorphisms were not associated with SVR, although a significantly higher percentage of -238 TNF-α genotype GG was detected in patients with significant liver fibrosis.
  
  
  CONCLUSIONS
  In HIV/HCV coinfected patients with HCV genotypes 1 or 4, RVR, mainly influenced by genotype IL28B and HCV-RNA levels, reliably predicted SVR after 4 weeks of therapy with Peg-IFN plus RBV. In patients infected by HCV genotype 3, an elevated relapse rate compromised the influence of RVR on SVR. Relapses were related to the presence of advanced liver fibrosis. Liver cirrhosis was associated with a -238 TNF-α polymorphism in these patients.
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Puerta del Mar, Cádiz, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Corchado
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba/Reina Sofia University Hospital, Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero-Juárez
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Torres-Cornejo
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba/Reina Sofia University Hospital, Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Puerta del Mar, Cádiz, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Márquez-Coello
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Puerta del Mar, Cádiz, Spain.
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Girón-González
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D060085:Coinfection / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D016174:Hepacivirus / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D012254:Ribavirin