Lens Sabela, Calleja Jose L, Campillo Ana, Carrión Jose A, Broquetas Teresa, Perello Christie, de la Revilla Juan, Mariño Zoe, Londoño María-Carlota, Sánchez-Tapias Jose M, Urbano-Ispizua Álvaro, Forns Xavier
Sabela Lens, Zoe Mariño, María-Carlota Londoño, Jose M Sánchez-Tapias, Xavier Forns, Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, 08036 Barcelona, Spain.
World J Gastroenterol. 2015 May 7;21(17):5421-6. doi: 10.3748/wjg.v21.i17.5421.
Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin. Pancytopenia due to myelotoxicity caused by these drugs may occur, but severe hematological abnormalities or aplastic anemia (AA) have not been described. We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011. Among 142 cirrhotic patients receiving treatment, 7 cases of severe pancytopenia (5%) were identified and three were consistent with the diagnosis of AA. Mean age was 59 years, five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation. Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy. Three patients had pre-treatment hematological abnormalities related to splenomegaly. In six patients, antiviral treatment was interrupted at the onset of hematological abnormalities. Two patients died due to septic complications and one patient due to acute alveolar hemorrhage. The remaining patients recovered. Severe pancytopenia and especially AA, are not rare during triple therapy with telaprevir in patients with advanced liver disease. Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.
特拉匹韦和博赛匹韦是首批被批准与聚乙二醇化干扰素α和利巴韦林联合用于治疗慢性丙型肝炎的直接抗病毒药物。这些药物引起的骨髓毒性可能导致全血细胞减少,但尚未见严重血液学异常或再生障碍性贫血(AA)的报道。自2011年该药获批以来,我们收集了西班牙四个中心在使用特拉匹韦进行三联疗法期间观察到的所有严重全血细胞减少病例。在142例接受治疗的肝硬化患者中,确诊7例严重全血细胞减少(5%),其中3例符合AA诊断。平均年龄59岁,5例患者为代偿期肝硬化,2例患者为肝移植后丙型肝炎严重复发。严重全血细胞减少在治疗开始后中位10周被诊断。3例患者治疗前存在与脾肿大相关的血液学异常。6例患者在血液学异常出现时中断了抗病毒治疗。2例患者死于感染并发症,1例患者死于急性肺泡出血。其余患者康复。在晚期肝病患者使用特拉匹韦进行三联疗法期间,严重全血细胞减少尤其是AA并不罕见。在此情况下必须密切监测,以便及时发现严重血液学疾病并预防进一步并发症。