Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
Hakodate City Hospital, Hokkaido, Japan.
Hepatol Res. 2015 Aug;45(8):837-45. doi: 10.1111/hepr.12421. Epub 2014 Oct 15.
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.
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.
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.
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.
替拉瑞韦为基础的慢性丙型肝炎患者的治疗是有效的;然而，皮肤反应的高发率是一个突出的问题。其不良反应的机制和特征尚不清楚;此外，预测因素仍然未知。颗粒溶素最近被报道在史蒂文斯-约翰逊综合征（SJS）患者的水疱中上调。因此，我们调查了严重替拉瑞韦诱导的皮肤反应的危险因素以及血清颗粒溶素水平与这些反应的严重程度之间的关系。
共分析了 89 例接受替拉瑞韦治疗且具有完整临床资料的患者。我们分析了皮肤反应与临床因素之间的关系。接下来，我们分别对 5 例和 14 例 3 级和非 3 级皮肤反应患者的血清颗粒溶素水平的时间依赖性变化进行了研究。
89 例患者中，57 例出现皮肤反应，其中 9 例为 3 级。单因素分析显示，3 级皮肤反应与男性显著相关。此外，血清颗粒溶素水平与皮肤反应的严重程度显著相关。3 例 3 级皮肤反应患者有严重的全身表现，包括 SJS、药物超敏反应综合征、全身淋巴肿胀和高热;所有患者均住院治疗。重要的是，在这 3 名患者中，有 2 名患者在发病时血清颗粒溶素水平超过 8ng/ml，症状在 6 天内恶化。
男性患者易发生严重的替拉瑞韦诱导的皮肤反应。此外，血清颗粒溶素水平与皮肤反应的严重程度显著相关，可能是替拉瑞韦治疗患者的预测因子。
