Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk - an observational, retrospective study

Abstract

The association between cytomegalovirus (CMV) reactivation and cardiovascular risk has been reported in solid organ transplant populations; however, it has yet to be assessed in liver transplantation (LT). We aim to evaluate whether CMV reactivation is associated with cardiovascular events (CVE) in HCV-LT patients. LT patients (2010 and 2014) due to HCV cirrhosis were included. Clinically significant CMV (CS-CMV) was defined as viral load (VL) >5000 copies/ml, need of therapy or CMV disease. Baseline variables and endpoint measures (CVE, survival, severe recurrent hepatitis C, de novo tumors, and diabetes) were collected. One hundred and forty patients were included. At LT, a history of AHT was present in 23%, diabetes 22%, tobacco use 45%, obesity 20%, and renal impairment (eGFR < 60 ml/min) in 26.5%. CS-CMV reactivation occurred in 25% of patients. Twenty-six patients (18.5%) developed a CVE. Cox regression analysis revealed two factors significantly associated with CVE: Pre-LT DM [HR = 4.6 95% CI (1.6, 13), P = 0.004] and CS-CMV [HR = 4.7 95% CI (1.8, 12.5), P = 0.002]. CS-CMV was not independently associated with the remaining endpoints except for survival (P = 0.03). In our series, CS-CMV reactivation was associated with a greater risk of developing CVE, thus confirming data from other solid organ transplant populations and emphasizing the need for adequate CMV control.

A Practical Review of Cytomegalovirus in Gastroenterology and Hepatology

“…The effects of CMV on allograft function extend beyond direct infection, however, as risks of acute and chronic allograft rejection are increased in patients with CMV infection [85]. Risks of bacteremia, invasive fungal disease, EBV-associated posttransplant lymphoproliferative disease, and cardiovascular disease are also increased in these patients [85, 89]. Therefore, despite the efficacy of treatment of CMV disease or infection with antiretrovirals, prevention is a major strategy in post-LT patients.…”

Role of cytomegalovirus infection after kidney transplantation on the subsequent risk of atherosclerotic and thrombotic events

“…These studies applied a variety of approaches to capture CMV exposure (from donor-recipient serostatus to pp65 antigenemia assay or molecular methods) and did not attempt to explore the temporal association between the presence, level and duration of CMV viremia and the subsequent incidence of cardiovascular complications. Moreover, a variety of events with different pathophysiologic mechanisms were often combined as a sole outcome, such as major cardiovascular events or atherosclerotic, thrombotic and/or embolic episodes [ 15 , 19 , 22 , 25 , 37 ]. In the present study we included a large cohort of KT recipients and used a thorough methodological approach to take into account the impact of cumulative CMV exposure at different time frames on the incidence of two separated outcomes, PAE and PTE, in the long-term follow-up.…”

HCV eradication in recurrent hepatitis C after liver transplantation normalizes enhanced endothelial activation

“…Finally, our study highlights the relevance of chronic viral infections in endothelial dysfunction and potential accelerated atherosclerosis after LT. Chronic HCV infection could serve as a model for other chronic viral infections such as cytomegalovirus, which has been associated with an increased risk of cardiovascular events in HCV LT patients [52]. Specific studies should evaluate the impact of chronic viral infections in endothelial activation and preclinical atherosclerosis in LT recipients.…”