Current concepts on cytomegalovirus infection after liver transplantation

Table 1 Direct and indirect clinical effects of cytomegalovirus 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 Chronic ductopenic rejection
Hepatitis	Hepatitis C virus recurrence
Pneumonitis	Allograft hepatitis, fibrosis and allograft failure
CNS disease
Retinitis
Mortality	Opportunistic and other infections
	Fungal superinfection
	Nocardiosis
	Bacterial superinfection
	Epstein-Barr virus and PTLD
	HHV-6 and HHV-7 infections
	Vascular thrombosis
	Mortality

PTLD: post-transplant lymphoproliferative disease; HHV: human herpes virus; CMV: cytomegalovirus.

¹Any organ system may be affected by CMV.

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

	Use of anti-cytomegalovirus prophylaxis
	Yes1 (%)	No (%)
CMV D+/R-	12-30	44-65
CMV D+/R+	2.70	18.20
CMV D-/R+	3.90	7.90
CMV D-/R-	0.00	0.00
All patients	4.80	18-29

D: donor; R: recipient; CMV: cytomegalovirus.

¹Most cases occur as delayed-onset CMV disease. CMV disease occurs rarely during prophylaxis with oral valganciclovir. Data adapted from references [4,5,77].

Table 3 Selected traditional and novel factors associated with increased risk of cytomegalovirus 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
Basiliximab
Human herpesvirus-6
Human herpesvirus-7
Renal insufficiency
Others1

D: donor; R: recipient; IL-10: interleukin-10; MCP-1: monocyte chemotactic protein-1; CCR5: chemokine (C-C motif) receptor 5; CMV: cytomegalovirus.

¹Others include re-transplantation, volume of blood transfusion, sepsis and other factors associated with high tumor necrosis factor-α secretion.

Table 4 Currently available antiviral drugs for cytomegalovirus prophylaxis and treatment in liver transplant recipients

Drug	Route	Usual adult prophylaxis dose	Usual adult treatment dose	Comments on use and major toxicity
Ganciclovir	Intravenous	5 mg/kg once daily	5 mg/kg twice daily	Intravenous access; leukopenia
Ganciclovir	Oral	1 g three times daily	Not applicable	Low oral bioavailability; high pill burden
Valganciclovir	Oral	900 mg once daily	900 mg twice daily	Ease of administration; leukopenia