Human herpesvirus 6 infections after liver transplantation

Table 1 Clinical syndromes attributed to HHV-6 after liver transplantation

HHV-6 direct effects	Ref.	HHV-6 indirect effects	Ref.
Fever and rash	[36]	Increased incidence and severity of cytomegalovirus disease	[314041]
Hepatitis	[333649]	Earlier and more severe recurrence of hepatitis C virus	[42]
Myelosuppression	[37]	Higher incidence of fungal infections	[44]
Pneumonitis	[37]	Higher incidence of opportunistic Infection	[36]
Neurologic illness	[384451]	Higher incidence of allograft rejection	[33364553]

HHV-6: Human herpesvirus 6.

Table 2 Tests for the laboratory diagnosis of HHV-6 infection

Test	Detects active infection	Distinguish HHV-6 variants A and B	Commercially available
Serology (IFA and ELISA)	No	No	Yes
Real time PCR
Qualitative	No	Yes	Yes1
Quantitative	Yes	Yes	Yes1
Culture	Yes	Yes	Yes2
Real time reverse transcriptase PCR	Yes	Yes	No3
Antigen testing	Yes	Yes	No
Antibody avidity testing	Yes	No	No
Immunohistochemical technique	Yes	Yes	No
PCR in situ	Yes	Yes	No

IFA: Immunofluorescence assay; ELISA: Enzyme-linked immunosorbent assay; PCR: Polymerase chain reaction;

¹Available at reference and commercial laboratories;

²Requires viral stimulation by chemicals;

³Very specialized research laboratories.

Table 3 Antiviral molecules and their activity against HHV-6

Antiviral drug	In vitro activity	In vivo activity1	Mechanism of antiviral resistance
Acyclovir[7381]	No	No
Ganciclovir[66–6870–72]	Yes	Yes	Mutation in U38 DNA polymerase
			Mutation in U69 phosphotransferase
Foscarnet[6582–85]	Yes	Yes2	Mutation in U38 DNA polymerase
Cidofovir[768695]	Yes	Yes	Mutation in U38 DNA polymerase
Maribavir[8788]	No	Not available
Cyclopropavir[89]	Yes	Not available
CMV 423[91]	Yes3	Not available
HDP-CDV[90]	Yes3	Not available
3 Deaza-HPMPA[92]	Yes	Not available

CMV 423: A New anti-CMV (Cytomegalovirus) molecule (2-chloro 3-pyridine 3-yl 5,6,7,8-tetrahydroindolizine 1-carboxamide); HDP-CDV: Hexadecyloxopropyl-cidofovir; 3 Deaza-HPMPA: (S)-9-[5-Hydroxy-2-(phosphonomethoxy) propyl]-3 deazaadenosine.

¹Based on very limited studies and case reports;

²Combination of foscarnet with ganciclovir or cidofovir has been reported and can be efficacious;

³Activity in vitro demonstrated against HHV6-A.