Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and virologic efficacy of ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) in the treatment of severe CMV infections in solid organ transplant recipients was investigated. Twelve patients (9 liver and 3 kidney transplant recipients) with CMV retinitis, esophagitis, hepatitis, or pneumonia received ganciclovir at a dose of 0.75-7.5 mg/kg/day for 10-30 days (mean duration 17 days). Clinical stabilization or improvement occurred in 8 patients (67%). Serial liver biopsies in 6 liver allograft recipients with CMV hepatitis demonstrated substantial histologic improvement on treatment. Of 6 patients with CMV pneumonia, 4 (67%) recovered and survived. Cultures of blood and other sites became negative in 9 patients (75%). Three patients (25%) had recurrent viral shedding after treatment, but none of these relapsed with invasive infections. Mild neutropenia was the only side effect encountered but was frequent (67%). The overall survival rate was 50%. Ganciclovir is effective in reducing CMV shedding in solid organ transplant recipients and is well tolerated. Our experience suggests a clinical benefit as well in patients with severe, invasive CMV disease. Relapse, in contrast to patients with the acquired immunodeficiency syndrome, is infrequent.
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PMID:Ganciclovir therapy of severe cytomegalovirus infections in solid-organ transplant recipients. 283 16

During childhood, many people acquire primary infection with cytomegalovirus (CMV), one of the herpes viruses. If they later become immunosuppressed, such as occurs with human immunodeficiency virus (HIV) infection, CMV is likely to become reactivated. Severe disease caused by CMV is life-threatening in the HIV-infected population. CMV retinitis, gastritis, colitis, pneumonia, encephalitis and hepatitis have all been reported, but oral lesions due to infection with CMV are rarely reported. We report a case of oral CMV infection which at first was clinically indistinguishable from HIV-associated periodontal disease.
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PMID:Cytomegalovirus infection presenting as acute periodontal infection in a patient infected with the human immunodeficiency virus. 838 96

Cytomegalovirus (CMV) infection was recognised in congenitally infected infants in the first half of the 20th century. Following the increased use of immunosuppressive regimens for bone marrow and solid organ transplantation, various manifestations of CMV disease were recognised. Milder symptoms included fever, anorexia and malaise but severe symptoms included pneumonitis, hepatitis, gastrointestinal ulceration, choreoretinitis and encephalopathy, all with a high morbidity or mortality. With the onset of the AIDS epidemic, manifestations of CMV became evident, predominantly retinitis. Ganciclovir used intravenously has been the principal anti-CMV agent investigated. However, ganciclovir has problems with suboptimal efficacy, toxicity, poor oral bioavailability and evolution of resistant strains. Additional studies have been performed on foscarnet and cidofovir, although the use of both have been limited by their nephrotoxicity. Combination therapy with ganciclovir and foscarnet for resistant strains has been used. There are promising newer drugs like the methylenecyclopropane nucleoside analogues and benzimidazole. The most novel compound is the antisense oligonucleotide fomivirsen that has been evaluated principally in CMV retinitis. The role of immunotherapy with either immunoglobulin prophylaxis or the novel adoptive immunotherapy needs further evaluation.
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PMID:Cytomegalovirus treatment options in immunocompromised patients. 1158 92

Cytomegalovirus (CMV) infection of the retina is a rarely encountered end-organ disease after transplantation. In order to describe the clinical characteristics and outcomes of CMV retinitis after hematopoietic stem cell and solid organ transplantation, we performed a retrospective review of all cases of CMV retinitis at the Mayo Clinic (Rochester, Minnesota) during 1990-2004. During this 15-year period, CMV retinitis was diagnosed in 14 eyes of 9 patients who had received kidney (n=5), liver (n=2), heart (n=1), and autologous hematopoietic stem cell transplant (n=1). The mean age of the patients was 58 (standard deviation+/-11) years; 6 were male. The median time to diagnosis of CMV retinitis was 9 months (range, 4 months to 13 years) after transplantation. Four (44%) patients had concomitant pneumonitis or hepatitis. Five (55%) patients had bilateral retinitis. Retinal involvement was <or=10% in 8 eyes, >10% but <or=50% in 4 eyes, and >50% in 2 eyes. All patients received induction therapy with intravenous ganciclovir (n=8) or foscarnet (n=1) for a median of 43 days (range, 14-100 days) followed by maintenance therapy with intravenous or oral ganciclovir for a median of 88 days (range, 36-943 days) in 6 (67%) patients. One patient developed bilateral immune recovery uveitis during treatment, and later on progressed to develop rhegmatogenous retinal detachment. During the mean follow-up period of 20 months, visual acuity improved in 4 (28.5%), was stable in 4 (28.5%), and worsened in 6 (43%) eyes. CMV retinitis recurred in 2 patients. In conclusion, CMV retinitis is a rare, progressive, and highly morbid infectious complication of transplantation. The severity of clinical disease at the time of diagnosis may predict poor outcome. Hence, early intervention may be crucial to prevent its progression to irreversible visual loss.
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PMID:Clinical features and outcomes of cytomegalovirus retinitis after transplantation. 1751 15

Human cytomegalovirus (HCMV) is a ubiquitous herpes virus (human herpes virus 5) with the highest morbidity and mortality rates compared to other herpes viruses. Risk groups include very young, elderly, transplant recipient, and immunocompromised individuals. HCMV may cause retinitis, encephalitis, hepatitis, esophagitis, colitis, pneumonia, neonatal infection sequelae, inflammatory, and age-related diseases. With an arsenal of genes in its large genome dedicated to host immune evasion, HCMV can block intrinsic cellular defenses and interfere with cellular immune responses. HCMV also encodes chemokines, chemokine receptors, and cytokines. Therefore, genes involved in human viral defense mechanisms and those encoding proteins targeted by the CMV proteins are candidates for host control of CMV infection and reactivation. Although still few in number, host genetic studies are producing valuable insights into biological processes involved in HCMV pathogenesis and HCMV-related diseases. For example, genetic variants in the immunoglobulin GM light chain can influence the antibody responsiveness to CMV glycoprotein B and modify risk of HCMV-related diseases. Moreover, CMV infection following organ transplantation has been associated with variants in genes encoding toll-like receptors (TLRs), programmed death-1 (PD-1), and interleukin-12p40 (IL-12B). A KIR haplotype (2DS4+) is proposed to be protective for CMV activation among hematopoietic stem cell transplant patients. Polymorphisms in the interferon lambda 3/4 (IFNL3/4) region are shown to influence susceptibility to CMV replication among solid organ transplant patients. Interestingly, the IFNL3/4 region is also associated with AIDS-related CMV retinitis susceptibility in HIV-infected patients. Likewise, interleukin-10 receptor 1 (IL-10R1) variants are shown to influence CMV retinitis development in patients with AIDS. Results from genome-wide association studies suggest a possible role for microtubule network and retinol metabolism in anti-CMV antibody response. Nevertheless, further genetic epidemiological studies with large cohorts, functional studies on the numerous HCMV genes, and immune response to chronic and latent states of infection that contribute to HCMV persistence are clearly necessary to elucidate the genetic mechanisms of CMV infection, reactivation, and pathogenesis.
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PMID:Host Genetics of Cytomegalovirus Pathogenesis. 3139 58