Winston D J, Wirin D, Shaked A, Busuttil R W
Department of Medicine, UCLA Medical Center 90024, USA.
Lancet. 1995 Jul 8;346(8967):69-74. doi: 10.1016/s0140-6736(95)92110-9.
Despite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p < 0.0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0.8%) ganciclovir patients (p = 0.002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p = 0.001) and negative patients (42 vs 11%, p = 0.06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p < 0.0001) and disease (p = 0.001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups. CMV can be eliminated almost completely as a significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe.
尽管目前有预防措施，但巨细胞病毒（CMV）仍是实体器官移植患者感染和发病的常见原因。因此，我们进行了一项对照试验，比较长期使用更昔洛韦与高剂量阿昔洛韦预防肝移植受者CMV感染和疾病的效果。移植时，患者被随机分为接受更昔洛韦组（术后第1天至第30天每天静脉注射6mg/kg体重，然后周一至周五每天6mg/kg，直至第100天）或阿昔洛韦组（术后第1天至出院每天每8小时静脉注射10mg/kg，然后每天口服800mg，每日4次，直至第100天）。通过频繁的培养、血清学检测、实验室测量和组织活检，对患者进行CMV感染、CMV疾病和药物相关毒性的随访。在移植后的前120天，126例阿昔洛韦组患者中有48例（38%）发生CMV感染，而124例更昔洛韦组患者中仅有6例（5%）发生感染（p<0.0001）。同样，126例阿昔洛韦组患者中有12例（10%）出现有症状的CMV疾病，而124例更昔洛韦组患者中仅有1例（0.8%）出现（p = 0.002）。更昔洛韦降低了CMV抗体阳性患者（37%对4%，p = 0.001）和阴性患者（42%对11%，p = 0.06）的CMV感染发生率。在对供体-受体CMV抗体状态和其他危险因素的多变量分析中，预防性使用更昔洛韦是预防CMV感染（p<0.0001）和疾病（p = 0.001）的最重要因素。更昔洛韦和阿昔洛韦一般耐受性良好。两组白细胞减少、血小板减少、肾衰竭和其他不良事件的发生率相似。通过长期预防性使用更昔洛韦，CMV几乎可以完全消除作为肝移植受者中的重要病原体。此外，该治疗方法是安全的。
