title: Severe Pulmonary Arterial Hypertension in Patients Treated for Hepatitis C With Sofosbuvir.
abstract: Development of direct-acting antiviral agents against hepatitis C virus (HCV) has changed the management of chronic HCV infection. We report three cases of newly diagnosed or exacerbated pulmonary arterial hypertension (PAH) in patients treated with sofosbuvir. All patients had PAH-associated comorbidities (HIV coinfection in two, portal hypertension in one) and one was already being treated for PAH. At admission, all patients presented with syncope, World Health Organization functional class IV, right-sided heart failure, and extremely severe hemodynamic parameters. After specific PAH therapy, the clinical and hemodynamic properties for all patients were improved. Severity and acuteness of PAH, as well as chronology, could suggest a causal link between HCV treatment and PAH onset. We hypothesize that suppression of HCV replication promotes a decrease in vasodilatory inflammatory mediators leading to worsening of underlying PAH. The current report suggests that sofosbuvir-based therapy may be associated with severe PAH.
authors.affiliation: Department of Cardiology, PAH Regional Expert Center, Hôpital de la Timone, Marseille, France. Electronic address: sebastien.renard@ap-hm.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Renard
authors.affiliation: Department of Hepato-Gastroenterology, Hôpital de la Timone, Marseille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Borentain
authors.affiliation: Department of Cardiology, PAH Regional Expert Center, Hôpital de la Timone, Marseille, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Salaun
authors.affiliation: Department of Cardiology, PAH Regional Expert Center, Hôpital de la Timone, Marseille, France.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Benhaourech
authors.affiliation: Department of Cardiology, PAH Regional Expert Center, Hôpital de la Timone, Marseille, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Maille
authors.affiliation: Central Pharmacy Service, Hôpital de la Conception, Marseille, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Darque
authors.affiliation: Department of Immuno-hematology, Hôpital Sainte Marguerite, Marseille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bregigeon
authors.affiliation: Institut hospitalo-universitaire Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique - Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UM63, CNRS 7278, IRD 198, Institut National de la Santé et de la Recherche Medicale U1095, Facultés de Médecine et de Pharmacie, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Colson
authors.affiliation: Regional Center of Pharmacovigilance, Provence-Alpes-Côte d'Azur-Corse, Hôpital Sainte Marguerite, Marseille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Laugier
authors.affiliation: Department of Pneumology, PAH Regional Expert Center, Hôpital Nord, Chemin des Bourrely, Marseille, France.
authors.forename: Martine Reynaud
authors.initials: MR
authors.lastname: Gaubert
authors.affiliation: Department of Cardiology, PAH Regional Expert Center, Hôpital de la Timone, Marseille, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Habib
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects*; D002219:Carbamates; D015897:Comorbidity; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000453:epidemiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D006975:Hypertension, Portal / Q000453:epidemiology; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012254:Ribavirin / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000009:adverse effects*; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: drug induced; hepatitis C virus; pulmonary arterial hypertension; sofosbuvir