Management of cytomegalovirus infection after liver transplantation

Table 1 Recommended approaches for cytomegalovirus prevention in liver transplantation[17]

CMV serostatus	Comments
D/R; low risk	Antiviral prophylaxis: CMV D-/R- LT recipients do not require anti-CMV prophylaxis; but if they are HSV1-or HSV2-seropositive, they should receive anti-HSV prophylaxis during the early period after LT (strong, high)
	Alternative: (1) Pre-emptive therapy (if higher risk, i.e., significant transfusions): If blood transfusion is required, CMV D/R patients should receive; and (2) CMV-seronegative or leuko-reduced blood products (strong, high)
D+/R+; D/R+; intermediate risk	Antiviral prophylaxis: (1) Drugs: valganciclovir1 900 mg po every 24 h; (2) ganciclovir 5 mg / kg (iv) 1×/d; and (3) duration: 3 months (strong, high)
	Alternative: (1) Pre-emptive therapy (if logistic support is available) (strong, high); (2) weekly CMV QNAT (or pp65 antigenemia) for 12 wk after LT; and (3) if a positive CMV threshold is reached, treat with valganciclovir 900 mg (po) BID (preferred), or ganciclovir 5 mg/kg (iv) every 12 h until negative test
D+/R; high risk	Antiviral prophylaxis: (1) Drugs: valganciclovir 900 mg (po) every 24 h; (2) ganciclovir 5 mg/kg (iv) 1×/d; and (3) duration: 3 mo (strong, high), 6 mo (strong, moderate)
	Alternative: (1) Pre-emptive therapy (if logistic support is available) (strong, high); (2) weekly CMV QNAT (or pp65 antigenemia) for 12 wk after LT; and (3) if a positive CMV threshold is reached, treat with valganciclovir 900 mg (po) BID (preferred), or ganciclovir 5 mg/kg (iv) every 12 h until negative test

¹Valgansiklovir use in LT recipients is not US FDA approved because of high rate of tissue-invasive disease, however experts still recommend its use for CMV prophylaxis in liver recipients (strong, moderate). Ease of administration. Leukopenia is major toxicity.

CMV: Cytomegalovirus; HSV: Herpes simplex virus; QNAT: Quantitative nucleic acid amplification test.

Table 2 Treatment of cytomegalovirus disease and algorithm for evaluation and management of refractory and resistant cytomegalovirus infection and disease[19]

CMV treatment
Valganciclovir 900 mg (po) BID (preferred), or ganciclovir 5 mg/kg (iv) every 12 h until negative test; antiviral treatment of CMV disease should be continued until the following criteria are met (strong, high): resolution of clinical symptoms, virological clearance below a threshold negative value based on laboratory monitoring with CMV QNAT or pp65 antigenemia once weekly, and minimum 2 wk of antiviral treatment
Suspect drug resistance1: (1) If cumulative ganciclovir exposure > 6 wk; and (2) if treatment failure after 2 wk of ongoing full dose ganciclovir or valganciclovir. Tests should be performed to detect specific mutations in the UL97 and UL54 genes. Decrease immunosuppressive therapy if possible. Assess severity of CMV infection. Definitive antiviral treatment should be guided by results of genotypic testing (strong, moderate to high)	Severe CMV disease present; foscarnet2 (add or switch); foscarnet 60 mg/kg IV every 8 h (or 90 mg/kg every 12 h)
	No severe CMV disease present; high (up to 10 mg/kg q 12 h, renally adjusted) or full dose (5 mg/kg bid iv) ganciclovir

¹Options for empiric treatment of suspected resistant cytomegalovirus (CMV) disease include high-dose intravenous ganciclovir (up to 10 mg/kg q 12 h, renally adjusted) or foscarnet (weak, low to moderate). Definitive antiviral treatment should be guided by results of genotypic testing (strong, moderate to high). Other therapeutic options are cidofovir (weak, low), participation clinical trials (e.g., maribavir treatment of refractory and resistant CMV) (strong, low), and off-label letermovir (weak, very low).

²Foscarnet, second-line alternative agent for treatment. Highly nephrotoxic. Used for UL97-mutant ganciclovir-resistant CMV infection or disease.

CMV: Cytomegalovirus; HSV: Herpes simplex virus; QNAT: Quantitative nucleic acid amplification test.