Martin M, Mañez R, Linden P, Estores D, Torre-Cisneros J, Kusne S, Ondick L, Ptachcinski R, Irish W, Kisor D
Department of Surgery, School of Pharmacy, University of Pittsburgh, Pennsylvania.
Transplantation. 1994 Oct 15;58(7):779-85. doi: 10.1097/00007890-199410150-00005.
Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07-6.56; P < 0.00001). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05-12.75; P = 0.0001). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P = 0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P = 0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population.
巨细胞病毒病是肝移植后发病的一个重要原因。迄今为止，尚无有效的肝移植后巨细胞病毒病预防措施。143例患者被随机分组，移植后3个月单独接受高剂量口服阿昔洛韦（800毫克，每日4次）（阿昔洛韦组），或静脉注射更昔洛韦（5毫克/千克，每日2次）14天，随后接受高剂量口服阿昔洛韦以完成3个月疗程（更昔洛韦组）。在139例可供评估的患者中，阿昔洛韦组71例患者中有43例（61%）发生巨细胞病毒感染，而更昔洛韦组68例中有16例（24%）（相对危险度，3.69；95%置信区间，2.07 - 6.56；P < 0.00001）。在随机分组的患者中，阿昔洛韦组20例（28%）出现巨细胞病毒病，而更昔洛韦组为6例（9%）（相对危险度，5.11；95%置信区间，2.05 - 12.75；P = 0.0001）。阿昔洛韦组巨细胞病毒感染发病的中位时间为45天，而更昔洛韦组为78天（P = 0.004）。阿昔洛韦组巨细胞病毒病发病的中位时间为40天，而更昔洛韦组患者为78天（P = 0.02）。关于原发性巨细胞病毒感染，两组发生率无差异，但更昔洛韦组组织侵袭性疾病和复发性巨细胞病毒病较少见。结论是，移植后立即给予2周更昔洛韦疗程，随后给予10周高剂量口服阿昔洛韦，在预防肝移植后巨细胞病毒感染和巨细胞病毒病方面优于单独12周高剂量口服阿昔洛韦疗程。然而，在接受血清学阳性供体移植物的血清学阴性受者中缺乏显著效果，提示需要其他策略来预防这一高风险人群的巨细胞病毒感染。
