Delayed‐onset cytomegalovirus disease coded during hospital readmission in a multicenter, retrospective cohort of liver transplant recipients

Abstract

Background Delayed-onset cytomegalovirus (CMV) disease can occur among liver transplant recipients after stopping CMV prophylaxis. We hypothesized that delayed-onset CMV disease (> 100 days post-transplant) occurs more commonly than early-onset CMV disease and is associated with clinical sepsis and death. Methods We assembled a large and more representative cohort of 7,229 adult liver transplant recipients from 26 transplant centers using 2004 to 2010 ICD-9-CM billing data from 4 Healthcare Cost and Utilization Project State Inpatient Databases, and identified demographics, comorbidities, CMV disease and clinical sepsis coded during readmission, and inpatient death. Multivariate analysis was performed using Cox proportional hazards models. Results Delayed-onset CMV disease occurred in 4.3% (n=309), while early-onset CMV disease occurred in 2% (n=142). Delayed-onset CMV disease was associated with previous transplant failure or rejection (aHR 1.4, 95% CI 1.1-1.7). Clinical sepsis > 100 days post-transplant was associated with previous CMV disease (aHR 1.3, 95% CI 1.0-1.7), previous transplant failure or rejection (aHR 2.1, 95% CI 1.8-2.4), female sex (aHR 1.3, 95% CI 1.1-1.5) and several comorbidities. Death > 100 days post-transplant was associated with delayed-onset CMV disease (aHR 2.0, 95% CI 1.6-2.6), transplant failure or rejection (aHR 4.3, 95% CI 3.4-5.5), increasing age (by decade: aHR 1.1, 95% CI 1.0-1.2) and some comorbidities. Conclusions Delayed-onset CMV disease is more common than early-onset CMV disease among liver transplant recipients. Previous CMV disease may be a risk factor for clinical sepsis > 100 days post-transplant, and delayed-onset CMV disease may be a risk factor for death > 100 days post-transplant.

It's not too late: a proposal to standardize the terminology of “late‐onset” cytomegalovirus infection and disease in solid organ transplant recipients

“…Instead, the vast majority of CMV disease in patients who received antiviral prophylaxis occurs shortly after discontinuation of antiviral drug use. This post‐discontinuation occurrence of CMV has been variably referred to in clinical studies as “late‐onset” CMV disease and “delayed‐onset” CMV disease . Although these terms have been used interchangeably, the timing of CMV may reflect different pathogenic processes, warranting the use of more specific terminology.…”

“…These studies indicate that the onset of CMV disease in these patients (at highest risk of “traditional‐onset” CMV disease) has only been “delayed” to the “late period” by antiviral prophylaxis. Because their onset varies in relation to the duration of prophylaxis, others have coined the term “delayed‐onset” CMV disease to describe cases of “traditional” CMV diseases that have only been “delayed” by antiviral prophylaxis .…”

Epidemiology of Bloodstream Infections in a Multicenter Retrospective Cohort of Liver Transplant Recipients

“…To determine the epidemiology of bloodstream infections after liver transplantation, we assembled a large and more representative cohort of liver transplant recipients from multiple centers using the Healthcare Cost and Utilization Project State Inpatient Databases (SID). The SID comprise of demographic and billing data that capture inpatient diagnoses and procedures through International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding 10 and has been used in the field of liver transplantation to study perioperative complications of live liver donors, 11 delayed-onset cytomegalovirus disease, 12 and relationships between hospital/surgeon volume and inpatient mortality. 13 The ICD-9-CM codes used to identify bloodstream infections in this study have been validated, with a positive predictive value of 89% and a negative predictive value of 80%.…”