title: Vascular ophthalmological side effects associated with antiviral therapy for chronic hepatitis C are related to vascular endothelial growth factor levels.
abstract: We have screened for the incidence of vascular ophthalmological side effects (VOSE) in chronic hepatitis C (CHC) patients undergoing pegylated interferon (peg-IFN) plus ribavirin (RBV) therapy and sought evidence for angiogenesis activation. Thirty-four CHC patients were prospectively evaluated (18 patients with 180 microg/week of peg-IFN-alpha2a plus 800mg/day of RBV and 16 with 1.5 microg/kg/week of peg-IFN-alpha2b plus 800-1,200mg/day of RBV). Complete ophthalmological evaluation and serum vascular endothelial growth factor (VEGF) levels were assessed before and at the end of therapy. Thirteen patients (38.2%) developed VOSE, eight (23.5%) featured subconjunctival haemorrhage, and five (14.7%) had evidence of retinopathy - all were unrelated to age, sex, genotype, the type of antiviral schedule used and response to therapy. At the end of treatment, the VOSE group had significantly higher serum VEGF levels than the group of patients without detectable side effects (median 281 [range 106-386] vs 117 [83-225] pg/ml, P=0.05). These differences increased when VEGF values were corrected by platelet count. In the VOSE group, baseline VEGF and VEGF/platelet values were also significantly higher (164 [55-260] vs 64 [21-172] pg/ml, P=0.046; and 0.920 [0.217-1.543] vs 0.320 [0.100-0.661] pg/10(6) platelets, P=0.024, respectively]. In a multivariate model VEGF/platelet values at end of treatment and hepatic fibrosis stage were the only predictors of VOSE development. In 3 out of 13 patients visual acuity was affected and 2 had residual lesions in the follow-up. In this exploratory study, antiviral therapy of CHC frequently induces VOSE, apparently through an activation of angiogenesis.
authors.affiliation: Liver Unit, University Hospital and School of Medicine, Málaga, Spain. andrade@uma.es
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
authors.forename: F Jesús
authors.initials: FJ
authors.lastname: González
authors.forename: Luis
authors.initials: L
authors.lastname: Vázquez
authors.forename: Angel
authors.initials: A
authors.lastname: Cilvetti
authors.forename: Raquel
authors.initials: R
authors.lastname: Camargo
authors.forename: Miren
authors.initials: M
authors.lastname: García-Cortés
authors.forename: Juan V
authors.initials: JV
authors.lastname: Martos-VanDussen
authors.forename: Pedro
authors.initials: P
authors.lastname: Rosón
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.forename: Encarnaciòn
authors.initials: E
authors.lastname: Clavijo
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005128:Eye Diseases / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011994:Recombinant Proteins; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D012254:Ribavirin / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a