Cytomegalovirus infection in liver transplant recipients: Updates on clinical management

Table 1 Direct and indirect clinical effects of cytomegalovirus in transplant recipients

Direct clinical effects	Indirect clinical effects
CMV syndrome	Acute allograft rejection
Fever > 38  °C for 2/4 d	Chronic allograft rejection
Malaise	Allograft failure
Myelosuppression	Vanishing duct syndrome/ductopenia
Tissue-invasive CMV disease1 Gastrointestinal disease (entire gastrointestinal tract can be affected)	Allograft hepatitis and fibrosis
	Vascular thrombosis
	Opportunistic and other infections
	Hepatitis	Fungal (Aspergillus, Pneumocystis)
Pneumonitis	Bacterial (Nocardia)
Retinitis	Viral (HHV-6, HHV-7, EBV)
CNS disease	Hepatitis C virus recurrence
Carditis	EBV associated PTLD
Mortality	Mortality

¹Can affect any organ, listed are most common organs affected. PTLD: Post-transplant lymphoproliferative disorder; HHV: Human herpes virus; EBV: Epstein-Barr virus; CMV: Cytomegalovirus.

Table 2 Comparison of antiviral prophylaxis and pre-emptive strategies for cytomegalovirus prevention in liver transplant patients

Prevention characteristics	Prophylaxis strategy	Pre-emptive strategy
CMV disease	Very effective at preventing CMV infection and disease	Effective to prevent CMV disease; does not prevent CMV infection
Late-onset CMV disease	Higher risk of late and very-late onset CMV disease	Reduces incidence of late onset CMV disease
Ideal treatment population	CMV D+R- are highest risk patients	CMV R+ patients
Logistics of strategy	Logistically more feasible, but still requires frequent monitoring of adverse effects	Requires weekly viral load testing; standardized viral load thresholds still being investigated
Cost	Higher drug costs; lower laboratory/monitoring costs	Higher laboratory/monitoring costs; lower drug costs
Safety/adverse effects	More frequent adverse effects such as myelosuppression due to longer treatment periods	Shorter treatment periods; fewer toxicities
Indirect CMV effects	Better evidence showing reduction of graft rejection, improved graft survival, opportunistic infections	Limited evidence overall, but may not reduce indirect effects
Effect on mortality	Reduces mortality from CMV disease	Limited evidence regarding mortality reduction
CMV resistance	More common compared to pre-emptive strategy	Some evidence regarding effect on resistance but overall uncommon

CMV: Cytomegalovirus.