Journal
TRANSPLANT INFECTIOUS DISEASE
Volume 10, Issue 1, Pages 27-43Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1399-3062.2007.00285.x
Keywords
cytomegalovirus; ganciclovir; resistance; immune reconstitution syndrome; liver transplantation; CMV late disease; chorioretinitis; immune reconstitution inflammatory syndrome; retinitis; vitritis
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A cytomegalovirus (CMV) donor positive/recipient negative liver transplant recipient developed CMV syndrome with presumed colitis 2 weeks after discontinuing the standard 3 months of valganciclovir prophylaxis. Treatment with intravenous ganciclovir (GCV) reduced, but did not clear, CMV replication. A CMV UL97 mutation (M460V) conferring GCV resistance was identified. Reduction of immunosuppression was followed by rapidly rising lymphocyte counts as well as by clearance of CMV viremia and of clinical symptoms. However, bilateral chorioretinitis was diagnosed 2 weeks later and treated with foscarnet and cidofovir. Then, right eye vitritis occurred necessitating vitrectomy due to a partially rhegmatogeneous retinal detachment. Because chorioretinitis-vitritis after rising lymphocyte counts and clearance of CMV viremia was strongly suggestive of an immune reconstitution syndrome (IRS)-like disease, we investigated CMV-specific T-cells in the peripheral blood available during follow-up. We found strong CD8(+) but only low CD4(+) T-cell responses (4.77% vs.<0.1%) to the CMV immediate early pp72, while responses to CMV-lysate or CMV-pp65 (CD4(+) <0.01%; CD8(+)<0.01%) were low. Over 16 weeks of follow-up, pp72-specific CD8(+) responses declined, while responses to pp65 gradually increased (CD4(+) 0.16%; CD8(+) 0.76%) indicating a slowly adapting CMV-specific cellular T-cell response. Review of 12,653 published liver transplant patients identified only 14 (0.1%) reported cases of CMV-associated chorioretinitis at a median 41.7 weeks post transplant. CMV-associated opthalmologic complications late post transplantation may possibly involve 2 different entities of cytopathic retinitis and IRS-like chorioretinitis-vitritis.
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