Cytomegalovirus infection after liver transplantation: Current concepts and challenges

Table 1 Direct and indirect clinical effects of CMV after solid organ transplantation

Direct effects	Indirect effects
CMV syndrome	Acute allograft rejection
Fever
Myelosuppression
Malaise
Tissue-invasive CMV disease1	Chronic allograft rejection
Gastrointestinal disease (colitis, esophagitis, gastritis, enteritis)	Vanishing bile duct syndrome
Hepatitis	Chronic ductopenic rejection
Pneumonitis
CNS disease	Hepatitis C virus recurrence
Retinitis	Allograft hepatitis, fibrosis and allograft failure
	Opportunistic and other infections
Mortality	Fungal superinfection
	Nocardiosis
	Bacterial superinfection
	Epstein-Barr virus and PTLD
	HHV-6 and HHV-7 infections
	Vascular thrombosis
	Mortality

¹Any organ system may be affected by CMV.

Table 2 Estimated incidence of CMV disease during the first 12 mo after liver transplantation

	Use of anti-CMV prophylaxis
	Yes1	No
CMV D+/R-	12%-30%	44%-65%
CMV D+/R+	2.7%	18.2%
CMV D-/R+	3.9%	7.9%
CMV D-/R-	0	0
All patients	4.8%	18%-29%

D: Donor; R: Recipient.

¹Most cases occur as delayed-onset CMV disease. CMV disease occurs rarely during prophylaxis with oral valganciclovir. Data adapted from[4,5,73].

Table 3 Selected traditional and novel factors associated with the increased risk of CMV disease after liver transplantation

Traditional factors	Recently identified factors
CMV D+/R- > CMV R+	Toll-like receptor gene polymorphism
Allograft rejection	Mannose binding lectin deficiency
High viral replication	Chemokine and cytokine defects (IL-10, MCP-1, CCR5)
Mycophenolate mofetil	Deficiency in CMV-specific CD4+ T cells
Muromonab-CD3	Deficiency in CMV-specific CD8+ T cells
Anti-thymocyte globulin	Expression of immune evasion genes
Alemtuzumab	Programmed cell death 1 expression
HHV-6
HHV-7
Renal insufficiency
Others1

¹Others factors include re-transplantation, volume of blood transfusion, sepsis and factors associated with high tumor necrosis factor-α secretion[1,4,11,13,21,39-42,77,89-93].