Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions

Goki Suda; Yoshiya Yamamoto; Astushi Nagasaka; Ken Furuya; Mineo Kudo; Yoshimichi Chuganji; Yoko Tsukuda; Seiji Tsunematsu; Fumiyuki Sato; Katsumi Terasita; Masato Nakai; Hiromasa Horimoto; Takuya Sho; Mitsuteru Natsuizaka; Kouji Ogawa; Shunsuke Ohnishi; Makoto Chuma; Yasuyuki Fujita; Riichiro Abe; Miki Taniguchi; Mina Nakagawa; Yasuhiro Asahina; Naoya Sakamoto; NORTE Study Group

doi:10.1111/hepr.12421

Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions

Hepatol Res. 2015 Aug;45(8):837-45. doi: 10.1111/hepr.12421. Epub 2014 Oct 15.

Authors

Goki Suda¹, Yoshiya Yamamoto², Astushi Nagasaka³, Ken Furuya⁴, Mineo Kudo⁵, Yoshimichi Chuganji⁶, Yoko Tsukuda¹, Seiji Tsunematsu¹, Fumiyuki Sato¹, Katsumi Terasita¹, Masato Nakai¹, Hiromasa Horimoto¹, Takuya Sho¹, Mitsuteru Natsuizaka¹, Kouji Ogawa¹, Shunsuke Ohnishi¹, Makoto Chuma¹, Yasuyuki Fujita⁷, Riichiro Abe⁷, Miki Taniguchi⁸, Mina Nakagawa⁸, Yasuhiro Asahina⁸, Naoya Sakamoto¹; NORTE Study Group

Affiliations

¹ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
² Hakodate City Hospital, Hokkaido, Japan.
³ Sapporo City General Hospital, Hokkaido, Japan.
⁴ Hokkaido Social Insurance Hospital, Hokkaido, Japan.
⁵ Sapporo Hokuyu Hospital, Hokkaido, Japan.
⁶ Tokyo Metropolitan Bokuto Hospital, Tokyo, Japan.
⁷ Department of Dermatology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
⁸ Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 25211174
DOI: 10.1111/hepr.12421

Abstract

Aim: 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.

Conclusion: 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.

Keywords: drug-induced hypersensitivity syndrome; granulysin; hepatitis C virus; telaprevir; toxic epidermal necrolysis.