title: Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions.
abstract: OBJECTIVE
  Telaprevir-based therapy for chronic hepatitis C patients is effective; however, the high prevalence of dermatological reactions is an outstanding issue. The mechanism and characteristics of such adverse reactions are unclear; moreover, predictive factors remain unknown. Granulysin was recently reported to be upregulated in the blisters of patients with Stevens-Johnson syndrome (SJS). Therefore, we investigated the risk factors for severe telaprevir-induced dermatological reactions as well as the association between serum granulysin levels and the severity of such reactions.
  
  
  METHODS
  A total of 89 patients who received telaprevir-based therapy and had complete clinical information were analyzed. We analyzed the associations between dermatological reactions and clinical factors. Next, we investigated the time-dependent changes in serum granulysin levels in five and 14 patients with grade 3 and non-grade 3 dermatological reactions, respectively.
  
  
  RESULTS
  Of the 89 patients, 57 patients had dermatological reactions, including nine patients with grade 3. Univariate analysis revealed that grade 3 dermatological reactions were significantly associated with male sex. Moreover, serum granulysin levels were significantly associated with the severity of dermatological reactions. Three patients with grade 3 dermatological reaction had severe systemic manifestations including SJS, drug-induced hypersensitivity syndrome, and systemic lymphoid swelling and high-grade fever; all were hospitalized. Importantly, among the three patients, two patients' serum granulysin levels exceeded 8 ng/mL at onset and symptoms deteriorated within 6 days.
  
  
  CONCLUSIONS
  Male patients are at high risk for severe telaprevir-induced dermatological reactions. Moreover, serum granulysin levels are significantly associated with the severity of dermatological reactions and may be a predictive factor in patients treated with telaprevir-based therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Goki
authors.initials: G
authors.lastname: Suda
authors.affiliation: Hakodate City Hospital, Hokkaido, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Sapporo City General Hospital, Hokkaido, Japan.
authors.forename: Astushi
authors.initials: A
authors.lastname: Nagasaka
authors.affiliation: Hokkaido Social Insurance Hospital, Hokkaido, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Furuya
authors.affiliation: Sapporo Hokuyu Hospital, Hokkaido, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Tokyo Metropolitan Bokuto Hospital, Tokyo, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Chuganji
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tsukuda
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsunematsu
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Terasita
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakai
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Horimoto
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sho
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Natsuizaka
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Chuma
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Riichiro
authors.initials: R
authors.lastname: Abe
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Asahina
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
keywords: drug-induced hypersensitivity syndrome; granulysin; hepatitis C virus; telaprevir; toxic epidermal necrolysis