Viral Infection

Viral illnesses tend to present within the first few months. Viral and bacterial illnesses are often seen concurrently. Ihe most common viral agent, and the most common cause of infection after transplantation, is CMV, a herpesvirus. It is reported to occur in between 23 and 85 percent of all liver transplant patients. Despite its high incidence and morbidity, it is rarely fatal unless disseminated and rarely has a significant effect on graft survival. It generally occurs within the first 3 months, with the peak incidence in the third and fourth weeks. Later occurrence is generally related to the need to increase immunosuppression for treatment of a prolonged episode of rejection. CMV can cause primary infection, or the infection can be a reactivation. Infection has three basic effects. First, it can produce a mononucleosis-like syndrome with spiking fever, arthralgias, malaise, neutropenia, atypical lymphocytes, and thrombocytopenia, with mild or moderate elevation in transaminase levels. Jaundice is rare. Second, CMV is frequently associated with opportunistic infection, which may be due to an additional immunosuppressive effect of its own. Finally, there is an increased propensity for allograft rejection.

Ihe patient may present with a pneumonitis that, when present, is characterized by bilateral interstitial infiltrates that may lead to adult respiratory distress syndrome. Diagnosis may require bronchoalveolar lavage, but the appearance of the chest x-ray and the clinical picture may be suggestive enough for diagnosis. CMV pneumonitis may be seen in conjunction with Pneumocystis carinii pneumonia (PCP). CMV hepatitis may present similarly to rejection, with fever, malaise, anorexia, abdominal pain, hepatomegaly, and liver dysfunction. Liver biopsy is frequently needed for diagnosis but still may not be able to distinguish CMV disease from rejection. Disseminated disease is frequently associated with an increase in immunosuppression, especially with treatment with OKI3. CMV chorioretinitis may present with decreased visual acuity, photophobia, scotomata, floaters, eye redness, or pain. Its presence signals a poor prognosis and the presence of profound immunosuppression.15

Ihere are three patterns of CMV infection. Ihe patient at greatest risk is the seronegative recipient of a seropositive donor. Disease may also be caused by reactivation of latent virus that replicates after the initiation of immunosuppression—typically in the seropositive recipient of a liver from a seronegative donor. Finally, a seropositive recipient may receive a liver from a seropositive donor, which may produce either reactivation or superinfection, although it is clinically impossible and irrelevant to distinguish between them.

Effective treatment depends on rapid diagnosis. Ireatment is with intravenous ganciclovir for 2 to 4 weeks. Diagnosis has been traditionally based on histology and culture. Standard fibroblast tube cell culture, however, can require 10 to 14 days for incubation. Serologic markers are too insensitive in the immunosuppressed patient, and electron microscopy is cumbersome. Ihe shell-vial technique can detect the presence of CMV after 16 h of incubation. It is an indirect immunofluorescence testing method that uses a monoclonal antibody directed at an early antigen of the virus. Early detection and high antigenemia correlate positively with the severity of the infection.

Other viruses may cause illnesses in the posttransplant patient. Up to 34 percent of all transplant patients develop HSV, and half of these present within the first 3 weeks. Mucocutaneous or genital disease is generally due to reactivation of latent infection. It is generally not severe, and diagnosis can be made with Izanck smear or culture. EBV can cause primary infection in children or the more common reactivated infection in adults. Ihe disease can be self-limited and cause a mononucleosis-like syndrome, with fever, tonsillitis, and lymphadenopathy, or it may progress to a polymorphous, multiorgan B-cell infiltrative process with high mortality. Finally, it may produce a localized solid tumor. EBV plays a role in the development of a posttransplantation lymphoproliferative disorder and has a high incidence (20 to 30 percent) in patients maintained on immunosuppression and higher (80 percent) in patients who have received antithymocyte antibody. 13 Adenovirus and enteroviruses may cause systemic illness but are uncommon.

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