Kirklin J K, Naftel D C, Levine T B, Bourge R C, Pelletier G B, O'Donnell J, Miller L W, Pritzker M R
Cardiac Transplant Research Database Center, University of Alabama at Birmingham.
J Heart Lung Transplant. 1994 May-Jun;13(3):394-404.
Cytomegalovirus infection is a major cause of morbidity and rehospitalization after heart transplantation. To assess its incidence and risk factors in the current era of heart transplantation, we analyzed cytomegalovirus infection data in 1553 patients from 26 institutions (Cardiac Transplant Research Database Group) undergoing primary heart transplantation between Jan. 1, 1990, and June 30, 1992. There were 230 treated cytomegalovirus infections in 200 patients, of which 16 were fatal (6%; 70% confidence limits 5% to 9%). Actuarial freedom from cytomegalovirus infection was 98% 1 month, 88% 3 months, and 83% 24 months after transplantation, with a peak incidence of initial infection at 2 months. Twenty-five (12%) of 200 patients with cytomegalovirus infection had recurrent cytomegalovirus infection during a mean follow-up of 13.9 months. The primary location of cytomegalovirus infection was blood in 100 infections (43%), lung in 69 (30%), gastrointestinal tract in 54 (23%), and other sites in seven patients (3%). Cytomegalovirus pneumonia exhibited the highest mortality rate (13%). Risk factors by multivariate analysis for earlier development of cytomegalovirus infection included pretransplantation cytomegalovirus serology (positive donor, negative recipient [p < 0.0001]; positive donor, positive recipient [p = 0.0002]; and negative donor, positive recipient [p = 0.02]) and cytolytic induction therapy (p = 0.05). A cytomegalovirus-positive recipient with a cytomegalovirus-positive donor had a 15% chance of having cytomegalovirus infection, whereas a cytomegalovirus-negative recipient with a cytomegalovirus-positive donor had a 24% chance. Ganciclovir treatment was administered in 227 (99%) of 230 infections. By multivariable analysis, the likelihood of a fatal cytomegalovirus infection was increased with a higher number of infections of any type during the first post transplantation month (p < 0.0001). There was no increased mortality rate in cytomegalovirus infections associated with cytomegalovirus-positive donor and cytomegalovirus-negative recipient (6% mortality rate) versus all other cytomegalovirus infections (6% mortality rate) (p = 0.9) or with OKT3 induction therapy (0% mortality rate) versus all others (noninduction and induction with other than OKT3) (1.4%) (p = 0.03). In conclusion, the biggest determinant of cytomegalovirus infection is donor and recipient pretransplantation cytomegalovirus serologic results with cytolytic induction therapy adding a small additional risk. The overall mortality rate from cytomegalovirus infections is low (7%) in the current era with rapid culture techniques and ganciclovir therapy. Cytomegalovirus infections are more likely to be fatal if there are more frequent preceding infections of any type, but mortality rates are not increased by OKT3 induction or with a cytomegalovirus-positive donor organ transplanted into a cytomegalovirus-negative recipient.
巨细胞病毒感染是心脏移植后发病和再次住院的主要原因。为评估在当前心脏移植时代其发病率及危险因素,我们分析了1990年1月1日至1992年6月30日期间26家机构(心脏移植研究数据库组)1553例接受初次心脏移植患者的巨细胞病毒感染数据。200例患者发生230次巨细胞病毒感染,其中16例死亡(6%;70%可信区间5%至9%)。移植后1个月、3个月和24个月巨细胞病毒感染的精算无感染率分别为98%、88%和83%,初次感染的高峰发病率在2个月时。200例巨细胞病毒感染患者中有25例(12%)在平均13.9个月的随访期间出现复发性巨细胞病毒感染。巨细胞病毒感染的主要部位为血液100例(43%)、肺69例(30%)、胃肠道54例(23%),7例(3%)为其他部位。巨细胞病毒肺炎死亡率最高(13%)。多因素分析显示,巨细胞病毒感染早期发生的危险因素包括移植前巨细胞病毒血清学检查结果(供体阳性、受体阴性[p<0.0001];供体阳性、受体阳性[p = 0.0002];供体阴性、受体阳性[p = 0.02])及细胞溶解诱导治疗(p = 0.05)。供体和受体均为巨细胞病毒阳性的患者发生巨细胞病毒感染的几率为15%,而供体为巨细胞病毒阳性、受体为巨细胞病毒阴性的患者发生感染的几率为24%。230次感染中有227次(99%)接受了更昔洛韦治疗。多变量分析显示,移植后第一个月内任何类型感染次数越多,发生致命性巨细胞病毒感染的可能性越大(p<0.0001)。供体为巨细胞病毒阳性、受体为巨细胞病毒阴性的巨细胞病毒感染与所有其他巨细胞病毒感染(死亡率6%)相比,死亡率无增加(p = 0.9);与OKT3诱导治疗(死亡率0%)相比,与所有其他治疗(非诱导治疗及非OKT3诱导治疗)(死亡率1.4%)相比,死亡率也无增加(p = 0.03)。总之,巨细胞病毒感染的最大决定因素是供体和受体移植前巨细胞病毒血清学检查结果,细胞溶解诱导治疗会增加小部分额外风险。在当前时代,随着快速培养技术和更昔洛韦治疗的应用,巨细胞病毒感染的总体死亡率较低(7%)。如果之前有更频繁的任何类型感染,巨细胞病毒感染更可能致命,但OKT3诱导治疗或供体为巨细胞病毒阳性器官移植给巨细胞病毒阴性受体不会增加死亡率。