Ganciclovir therapy for cytomegalovirus-associated liver disease in immunocompetent or immunocompromised children

Abstract

Ganciclovir therapy was given intravenously to 20 children with cytomegalovirus (CMV)-associated liver disease, of whom 6 were immunocompetent and 14 were immunocompromised (9 had AIDS and 5 had solid tumors). Immunocompetent children had isolated liver disease diagnosed at birth (4 children), or systemic congenital CMV infection including liver disease (2 children). Ganciclovir was used following two regimens: A) 5 mg/kg twice daily for 8 to 86 days (mean 21); B) 7.5 mg/kg twice daily for 14 days followed by 10 mg/kg three times weekly for three months. CMV infection was diagnosed by viral isolation, detection of viral antigens, and/or CMV DNA from blood and urine. All immunocompetent children had negative CMV culture and CMV DNA detection from blood and/or urine after 14 weeks of treatment. However, the three children who were treated with regimen B showed normal ALT levels at the end of the maintenance course, whereas the children who received ganciclovir with regimen A had normal ALT levels only after about 1 year. All children with tumors initiated regimen B, but only three, who had negative CMV detection and markedly decreased ALT levels, received full treatment; of the remaining two children, one recovered after only an initial course, and the other had therapy interrupted because of hepatic failure and died 9 days later. In contrast, the children with AIDS received several ganciclovir courses for different periods at the lower dosage: they generally improved during treatment but did not recover completely, and five children died with active CMV infections. Based on our study, CMV-associated liver disease can be efficiently treated with ganciclovir both in immunocompetent and immunodeficient children. However, a single ganciclovir course including a higher dosage and prolonged therapy appeared to be more effective than several courses with lower dosages.

Cytomegalovirus Infection in Infantile Hepatitis

“…It has been reported that, rarely, acute CMV infection in patients with normal immune systems can cause massive hepatocellular necrosis and coagulopathy [28]. There are reports of effective ganciclovir treatment of acute CMV hepatitis in immunocompetent children [29,30]. Also, biochemical, serological, virological improvements have been reported in cases of neonatal cytomegalovirus cholestatic hepatitis treated with ganciclovir [31].…”

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

“…The first reports of the use of ganciclovir therapy for congenital CMV infection date to the late 1980s (75,206). In subsequent reports (16,60,76,117,124,175,185,186,220,272), ganciclovir has been shown to be generally safe and well tolerated when used in newborns and has appeared to be useful in the management of severe, focal end-organ disease (pneumonitis, hepatitis, etc.) in infants.…”

Ganciclovir for Severe Cytomegalovirus Primary Infection in an Immunocompetent Child

“…An unusual aspect of the case is that the child had never presented previously with a disease suggestive of an immunodeficiency. In contrast with perinatal CMV infection, which can be a severe disease [2,3,4,5], CMV infection later in life is generally asymptomatic in immunocompetent children and adults. In rare cases, a self-limited mononucleosis-like syndrome with mild liver-test abnormalities can be present.…”

“…However, antiviral therapy can be beneficial in immunocompetent hosts, including adults, with severe acute or persistent CMV infection, as reported in a limited number of cases [3,5,6]. For example, nine immunocompetent infants and children aged 20 days to 33 months each received a 2-week-course of intravenous ganciclovir (n=6) in association with anti-CMV immunoglobulin (n=2) or anti-CMV immunoglobulin alone (n=1) for severe CMV disease [3,5].…”