title: Dermatologic adverse events of protease inhibitor-based combination therapy in patients with chronic hepatitis C.
abstract: BACKGROUND
  Combination therapy with pegylated interferon, ribavirin and a first-generation NS3/4A protease inhibitor, telaprevir or boceprevir, is the new strategy for treatment of genotype 1 chronic hepatitis C virus infection. This combination improves therapeutic efficacy but it also increases the risk of adverse events.
  
  
  OBJECTIVE
  The aim of the study was to analyze frequency and severity of dermatological adverse events during protease inhibitor-based therapy and to evaluate the risk factors for their development.
  
  
  METHODS
  This is a retrospective study of 109 patients with genotype 1 chronic hepatitis C treated with boceprevir (n=33) or telaprevir (n=76) based triple therapy. A logistic regression for relationship between clinical, demographic and laboratory factors and cutaneous adverse events was performed.
  
  
  RESULTS
  Dermatological adverse events (skin rash, pruritus, anorectal paresthesia) occurred in both treatments (boceprevir and telaprevir) with similar frequency: 28% in telaprevir and 21% in boceprevir. In patients treated with telaprevir, men were more predisposed to develop skin rashes compared to women (OR 4,1 p=0,014) and age above 45 years was associated with occurrence of pruritus in men (OR 8,16 p=0,014). Being a female, coexistence of autoimmune thyroiditis and advanced liver fibrosis were independent factors predisposing to development of anorectal paresthesia (OR 4,13 p=0,041, OR 4,25 p=0,029, OR 4,54 p=0,018 respectively) in this group. In patients treated with boceprevir, coexistence of autoimmune thyroiditis predisposed to skin rashes (OR 10,22 p=0,017) and being a female predisposed to pruritus (OR11,2 p=0,033). The adverse events occurred after a mean time of 8,6 (range 1-24) weeks after initiation of therapy.
  
  
  CONCLUSIONS
  In patients with chronic hepatitis C who received the triple therapy, the anorectal paresthesias were observed only in patients treated with telaprevir. The predisposing factors for this adverse event were: female gender and advanced liver fibrosis. The risk factors for other dermatological adverse were: 1) being a male over 45 years, for skin rashes and pruritus (for telaprevir), 2) coexistence of autoimmune thyroiditis for skin rashes (for boceprevir), 3) being a female, for pruritus (for boceprevir).
authors.affiliation: Department of Dermatology Provincial Hospital, Kielce, Poland;
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kłujszo
authors.affiliation: Department of Dermatology Provincial Hospital, Kielce, Poland;
authors.forename: Piotr
authors.initials: P
authors.lastname: Parcheta
authors.affiliation: Department of Infections Disease Provincial Hospital, Kielce, Department of Health Science, Jan Kochanowski University, Kielce, Poland;
authors.forename: Dorota
authors.initials: D
authors.lastname: Zarębska-Michaluk
authors.affiliation: Department of Animal Physiology, Jan Kochanowski University, Kielce, Poland;
authors.forename: Ewa
authors.initials: E
authors.lastname: Ochwanowska
authors.affiliation: Student of Medicine faculty, University of Szeged, Hungary;
authors.forename: Anna
authors.initials: A
authors.lastname: Witkowska
authors.affiliation: Department of Dermatology, Medical University of Warsaw, Poland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Rakowska
authors.affiliation: Department of Dermatology, Medical University of Warsaw, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Rudnicka
authors.affiliation: Department of Infections Disease Provincial Hospital, Kielce, Department of Health Science, Jan Kochanowski University, Kielce, Poland;
authors.forename: Wiesław
authors.initials: W
authors.lastname: Kryczka
keywords: boceprevir; interferon; itch; liver; peginterferon; skin; telaprevir; viral infection