valganciclovir and Epstein-Barr-Virus-Infections

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine the recommended phase 2 dose (RP2D) for phase 2 expansion. Phase 2 patients (n = 30) received RP2D (nanatinostat 20 mg daily, 4 days per week with valganciclovir 900 mg orally daily) for 28-day cycles. The primary end points were safety, RP2D determination (phase 1b), and overall response rate (ORR; phase 2). Overall, 55 patients were enrolled (B-non-Hodgkin lymphoma [B-NHL], [n = 10]; angioimmunoblastic T-cell lymphoma-NHL, [n = 21]; classical Hodgkin lymphoma, [n = 11]; and immunodeficiency-associated lymphoproliferative disorders, [n = 13]). The ORR was 40% in 43 evaluable patients (complete response rate [CRR], 19% [n = 8]) with a median duration of response of 10.4 months. For angioimmunoblastic T-cell lymphoma-NHL (n = 15; all refractory to the last prior therapy), the ORR/CRR ratio was 60%/27%. The most common adverse events were nausea (38% any grade) and cytopenia (grade 3/4 neutropenia [29%], thrombocytopenia [20%], and anemia [20%]). This novel oral regimen provided encouraging efficacy across several EBV+ lymphoma subtypes and warrants further evaluation; a confirmatory phase 2 study (NCT05011058) is underway. This phase 1b/2 study is registered at www.clinicaltrials.gov as #NCT03397706.

Topics: Adolescent; Adult; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Histone Deacetylase Inhibitors; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Neoplasm Recurrence, Local; Thrombocytopenia; Valganciclovir

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are a significant cause of morbidity and mortality in transplant recipients and are often transmitted from the donor organ.. In a pilot prospective, randomized, double-blinded, placebo-controlled trial, we studied whether 14 days of pretransplant donor treatment with valganciclovir (valG) versus placebo reduced donor-to-recipient transmission, making posttransplant recipient prophylaxis more effective in reducing EBV and CMV disease.. Seventeen D+ R- donor-recipient pairs were enrolled: 7 and 10 donors were randomized to valG and placebo, respectively. At study initiation, no donor had detectable CMV replication, five had EBV replication (two in valG, three in placebo group): EBV replication was undetectable during valG treatment, but resumed on stopping valG. Valganciclovir was tolerated without side effects or leukopenia. All recipients received routine posttransplant viral prophylaxis with valG. For recipients, viremia-free survival time, incidence, range, peak, and duration of CMV and EBV viremia were not significantly different between groups. There was no disease in the valG group but two serious viral diseases occurred in the placebo group (one CMV; one EBV-related posttransplant lymphoproliferative disorder). In the case of posttransplant lymphoproliferative disorder, the EBV DNA from the donor's oral wash and the recipient's lymphoid tissue biopsy had identical latent membrane protein 1 (LMP-1) sequence variations from the reference EBV strain, making it highly probable that the recipient's virus was of donor origin.. Based on this pilot trial, we recommend an adequately powered study to determine if pretransplant donor treatment with valG can reduce posttransplant CMV and EBV disease with merely routine posttransplant recipient viral prophylaxis.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus Infections; Double-Blind Method; Epstein-Barr Virus Infections; Female; Ganciclovir; Humans; Infant; Kidney Transplantation; Living Donors; Male; Middle Aged; Pilot Projects; Prospective Studies; Valganciclovir; Viremia; Virus Replication; Young Adult

A series of substudies of a large international cytomegalovirus (CMV) prophylaxis trial investigated the incidence and clinical relevance of reactivation of human herpesviruses 6, 7, and 8, varicella zoster virus, Epstein-Barr virus, polyomavirus, and adenovirus, and the effect of CMV prophylaxis on clinical and subclinical non-CMV viral infections, in adult solid organ transplant (SOT) patients. Results of the substudy analyses showed that viremia caused by a number of viruses is surprisingly common posttransplantation; most of these infections likely represent reactivation of endogenous latent virus. In addition, although infection or active viral replication was common in this cohort of SOT patients, symptomatic disease due to these viruses was uncommon and the clinical sequelae of viremia were unclear or not apparent. CMV prophylaxis may have modified the natural history of some of these non-CMV viral infections.

Topics: Antiviral Agents; BK Virus; Cytomegalovirus Infections; Double-Blind Method; Epstein-Barr Virus Infections; Ganciclovir; Herpesvirus 4, Human; Herpesvirus 6, Human; Herpesvirus 7, Human; History, 16th Century; Humans; Organ Transplantation; Polyomavirus Infections; Postoperative Complications; Valganciclovir; Viremia; Virus Activation

Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression.. We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir.. Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study.. Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients.. These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.

Topics: Administration, Oral; Adult; Antibodies, Viral; Antiviral Agents; Central Nervous System Diseases; Epstein-Barr Virus Infections; Fatigue Syndrome, Chronic; Female; Ganciclovir; Herpesvirus 4, Human; Herpesvirus 6, Human; Humans; Immunoglobulin G; Male; Middle Aged; Roseolovirus Infections; Valganciclovir

The role of antiviral prophylaxis to prevent Epstein-Barr virus (EBV) viremia or posttransplant lymphoproliferative disorder in pediatric solid organ transplant recipients is controversial. We examined whether valganciclovir (VAL) prophylaxis for cytomegalovirus infection was associated with EBV viremia following transplantation in EBV-naive children.. A single-center, retrospective study was conducted of EBV-naive pediatric heart and renal transplant recipients with an EBV-positive donor from January 1996 to April 2017. VAL was tested for association with EBV viremia-free survival in the first 6 months posttransplantation when immunosuppressant exposure is the highest. Survival models evaluated VAL duration, with adjustment for other baseline confounders.. Among the cohort (n = 44), 3 (6.8%) were heart transplants, 25 (56.8%) received VAL, and 22 (50%) developed EBV viremia in the first-year posttransplantation. Mean time-to-viremia was 143 vs. 90 days for the VAL and no-VAL groups, respectively (p = 0.008), in the first 6 months. Only two patients developed viremia while on VAL. Each additional day of VAL was associated with 1.4% increase in viremia-free survival (p < 0.001). Multivariable modeling of VAL with other baseline risk factors did not identify other independent risk factors.. VAL is independently associated with delayed onset of EBV viremia, with prolongation of delay with each additional day of antiviral prophylaxis.

Topics: Adolescent; Antiviral Agents; Child; Disease-Free Survival; Epstein-Barr Virus Infections; Female; Graft Survival; Humans; Immunosuppression Therapy; Male; Multivariate Analysis; Organ Transplantation; Proportional Hazards Models; Retrospective Studies; Transplant Recipients; Valganciclovir; Viremia

CMV is associated with adverse effects in renal transplant recipients. The objective of this study was to characterize the incidence and timing of CMV and EBV infections in relation to valGCV prophylaxis in a pediatric renal transplant cohort.. Retrospective cohort of pediatric renal transplant patients given universal valGCV prophylaxis and universal viral surveillance was evaluated. Demographics, prophylaxis, acute rejection, and CMV and EBV infections were abstracted.. A total of 92 pediatric renal allograft recipients, 2008-2013, were included. One or more viral infections developed in 77/92 (83.7%) of the patients. EBV was the most common in 62/92 (67%) patients, irrespective of valGCV (82% of episodes occurring on valGCV). CMV DNAemia occurred in 30/92 (33%) patients, 14 episodes (47%) occurring on valGCV. Incidence of breakthrough CMV on prophylaxis was 15% and was associated with persistent DNAemia (OR 7.8, CI:1.6-32.9, P < 0.02). CMV tissue-invasive disease was not seen. CMV syndrome occurred in 10% of the cohort, only in CMV D+ patients, and only one symptomatic breakthrough infection required treatment. Out of 92, 21 (23%) had simultaneous co-infections with 2-3 viruses.. Viral infections in pediatric renal transplant recipients receiving universal valGCV prophylaxis were common. EBV infections were not reduced by valGCV prophylaxis, and nearly half of CMV infections occurred on valGCV. Symptomatic CMV infection while on prophylaxis was rare. valGCV prophylaxis may prevent symptomatic CMV infection but not EBV infection, and frequent CMV surveillance in pediatric renal transplant recipients on prophylaxis may not be necessary.

Topics: Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Female; Ganciclovir; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Polymerase Chain Reaction; Retrospective Studies; Transplant Recipients; Valganciclovir

Topics: Antibiotic Prophylaxis; Biopsy; Child; Epstein-Barr Virus Infections; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lymph Nodes; Lymphadenopathy; Male; Nephrotic Syndrome; Postoperative Complications; Valganciclovir

This study evaluated the efficacy of prophylactic ValGCV in preventing CMV and EBV infections in a single-center pediatric kidney transplant population (2008-2014). Therapy duration was determined according to donor/recipient serostatus. EBV monitoring was performed using monthly plasma PCR for 18 months post-transplant and for CMV, monthly for 6 months after prophylaxis cessation. Data were collected on 35 children, median age 10.6 years. There were 15 (42.9%) and 11 (31.4%) recipients seronegative for CMV or EBV, respectively, who received a kidney from a seropositive donor. Prophylaxis was ceased by 6 months in 24 (69%), between seven and 13 months in 10 (29%) children. Fourteen (40%) and eight (23%) children experienced CMV and EBV DNAemia, respectively. Ten of the 14 (71%) episodes of CMV DNAemia occurred in the first 6 months following cessation of prophylaxis. Shorter prophylaxis was associated with increased CMV DNAemia (P = 0.044). There was an inverse correlation between adjusted ValGCV dose and EBV incidence/timing. Neutropenia was more common if ValGCV dosage was ≥10% of the dose predicted (by BSA and creatinine clearance). ValGCV prevents CMV and may modify EBV infection risk. Frequent dosing adjustment for BSA and creatinine clearance is required to optimize safety and efficacy.

Topics: Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Female; Ganciclovir; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Infant; Kidney Transplantation; Male; Neutropenia; Polymerase Chain Reaction; Retrospective Studies; RNA, Viral; Tissue Donors; Valganciclovir

Topics: Aged; Antiviral Agents; Disease Susceptibility; Epstein-Barr Virus Infections; Ganciclovir; Herpesvirus 4, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Nitriles; Primary Myelofibrosis; Pyrazoles; Pyrimidines; Stomach Ulcer; Valganciclovir

This study sought to evaluate in pediatric liver transplant recipients the effects of hybrid antiviral therapy on the rate of posttransplant lymphoproliferative disorder.. All pediatric patients (87 cases) who had undergone a liver transplant between April 2011 and March 2012 took part in the study and received hybrid antiviral treatment (case group). Epstein-Barr virus polymerase chain reaction was monitored intermittently. The results were compared to those of a historical control group including 117 pediatric patients who received a liver transplant between April 2009 and March 2011. Follow-up was 27 to 47 months in the control group and 12 to 26 months in the case group.. Posttransplant lymphoproliferative disorder occurred in 12 patients in control group (10.2%) and 5 patients in case group (5.7%) (P = .249). Of 12 cases of posttransplant lymphoproliferative disorder, death occurred in 5 cases in the control group (41.7%), while no posttransplant lymphoproliferative disorder-associated death was seen in the case group (P = .086).. Although hybrid antiviral treatment did not result in a statistically significant decrease in posttransplant lymphoproliferative disorder and posttransplant lymphoproliferative disorder-associated mortality rates, considering the limited number of posttransplant lymphoproliferative disorder cases in this study, this decrease may be interpreted as noticeable, and we advise using this strategy for pediatric patients undergoing a liver transplant.

Topics: Administration, Intravenous; Administration, Oral; Age Factors; Antiviral Agents; Biomarkers; Case-Control Studies; Child; Child, Preschool; DNA, Viral; Drug Administration Schedule; Drug Therapy, Combination; Epstein-Barr Virus Infections; Female; Ganciclovir; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Incidence; Infant; Iran; Liver Transplantation; Lymphoproliferative Disorders; Male; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir; Viral Load

Donor corneas with narrow scleral rims are often disqualified for Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK), mainly because of fluid leak and low pressure when they are mounted onto an artificial anterior chamber (AAC). This report describes a novel method to tight-lock a donor cornea with a narrow scleral rim so that microkeratome cutting is possible, allowing a DSAEK procedure to be completed. A 50-year-old male suffering from Epstein-Barr virus (EBV) endotheliitis with resulting corneal edema in his left eye was the subject of this study. His best corrected visual acuity (BCVA) was 20/600. The patient underwent a DSAEK procedure; however, the microkeratome cutting of the donor cornea initially failed due to its narrow scleral rim, which caused the balance salt solution (BSS) to leak out of the AAC. A doughnut-shaped cushion was made from a surgical glove, which enabled a tight lock of the cornea to the AAC, enabling the chamber pressure to be raised and the microkeratome cutting to be completed. A subsequent DSAEK procedure was performed uneventfully. Postoperatively, the patient received oral valganciclovir 450 mg b.i.d. to prevent EBV recurrence. The graft remained clear at 5 months post-op, and the patient's BCVA improved to 6/7.5. His endothelial count was 1830, which was ∼ 79% of the original value. Inserting a self-made cushion can enable donor corneas with narrow scleral rims to be used in DSAEK procedures and avoids unwanted switching from endothelial keratoplasty to penetrating keratoplasty (PKP).

Topics: Antiviral Agents; Cornea; Descemet Stripping Endothelial Keratoplasty; Epstein-Barr Virus Infections; Ganciclovir; Humans; Male; Middle Aged; Sclera; Valganciclovir

Described is the case of a 21-year-old male patient who presented with a severe Epstein-Barr virus (EBV) hepatitis. The initial diagnosis was challenging, as the patient did not have the typical features of the mononucleosis syndrome and despite the severity of the hepatitis, the initial serology was negative. In addition the liver biopsy did not show the mononuclear cell infiltration typically seen in EBV hepatitis. Later, measurements of EBV DNA showed high titers and the patient received a course of oral valganciclovir, following which he made a rapid clinical and serological response. This case describes an unusual presentation of EBV hepatitis, and adds to the body of evidence supporting its treatment with valganciclovir.

Topics: Antiviral Agents; DNA, Viral; Epstein-Barr Virus Infections; Ganciclovir; Hepatitis, Viral, Human; Humans; Male; Treatment Outcome; Valganciclovir; Young Adult

Reactivation of latent herpes viruses occurs with immunosuppression. Alemtuzumab is an antibody targeting CD52, which is expressed on all B- and T-cells. Treatment with alemtuzumab leads to profound T-cell suppression, and reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) occurs. Valganciclovir is used as an anti-CMV prophylaxis during alemtuzumab therapy.. To determine if EBV reactivation is decreased with valganciclovir prophylaxis.. Plasma EBV DNA was serially quantified by quantitative polymerase chain reaction with a World Health Organization EBV standard in patients receiving alemtuzumab therapy with valganciclovir as anti-CMV prophylaxis.. Twenty-nine patients were studied. A total of 258 samples were quantified, at a median of 7 (3-25) specimens per patient. Twenty-four patients never had any quantifiable EBV DNA. Five patients (17%) developed EBV reactivation. Two patients had EBV reactivation at very low levels of about 10(3)IU/mL, 3-4 logs lower than those typically found in post-transplant lymphoproliferative diseases. Three patients had EBV reactivation at higher levels of 10(4)IU/mL, which only occurred after two courses of alemtuzumab were administered. EBV reactivation subsided spontaneously in four cases. One patient developed EBV-positive Hodgkin lymphoma, but he had also received previously another potent T-cell suppressing drug fludarabine.. Valganciclovir suppressed EBV reactivation during alemtuzumab therapy. It might be a useful prophylaxis in immunocompromized patient populations at high risk of EBV reactivation.

Topics: Aged; Aged, 80 and over; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antiviral Agents; Chemoprevention; DNA, Viral; Epstein-Barr Virus Infections; Female; Ganciclovir; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Male; Middle Aged; Polymerase Chain Reaction; Valganciclovir; Viral Load; Virus Activation

Epstein-Barr virus (EBV) is a common infection which usually produces mild or no symptoms in immunocompetent individuals. In human immunodeficiency virus (HIV) associated immunosuppression it is most commonly associated with malignancy which usually occurs at very low CD4+ cell counts. We describe a newly diagnosed HIV-positive patient who presented with headaches and cerebellar signs. She was incorrectly diagnosed with cerebral tuberculosis (TB) infection based on the histology report from a cerebellar biopsy specimen. After extensive investigation including cerebrospinal fluid sampling and reanalysis of the brain biopsy specimens she was found to have EBV-associated cerebral vasculitis and encephalitis and was successfully treated with valganciclovir and steroids. Whilst there are a few reports of EBV-associated encephalitis, cerebral vasculitis secondary to EBV in the context of HIV infection has not previously been described in the literature.

Topics: Adult; Anti-Inflammatory Agents; Antiviral Agents; Encephalitis, Viral; Epstein-Barr Virus Infections; Female; Ganciclovir; HIV Infections; Humans; Steroids; Treatment Outcome; Valganciclovir; Vasculitis, Central Nervous System

We describe the case of an 18-year-old immunocompetent male patient with severe hepatitis during primary Epstein-Barr virus infection, treated with oral valganciclovir. During the initial therapy with corticosteroids, the patient's clinical condition and liver function worsened, so we decided to add oral valganciclovir for its good bio-availability and previous encouraging experiences in different clinical settings, with rapid resolution of the symptoms.

Topics: Adolescent; Antiviral Agents; Epstein-Barr Virus Infections; Ganciclovir; Hepatitis, Viral, Human; Humans; Male; Treatment Outcome; Valganciclovir

Epstein-Barr virus (EBV) primary infection constitutes a serious risk for pediatric transplant recipients, particularly as regards the development of EBV-related post-transplant lymphoproliferative disease (PTLD). Currently, there is no established prophylactic regimen. We investigated the association between chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) and the incidence of EBV viremia in EBV-naïve pediatric renal transplant recipients (R-) who had received a graft from an EBV-positive donor (D+) and are therefore at high risk of EBV primary infection. In a prospective, multicenter trial (n = 114), we compared a cohort on chemoprophylaxis (n = 20) with a similar control cohort without chemoprophylaxis (n = 8). Over the 1-year study period, antiviral prophylaxis with VGCV/GCV was associated with a significantly decreased incidence of EBV primary infection: 9/20 patients (45%) in the prophylaxis group experienced an EBV primary infection compared to 8/8 controls (100%) (P < 0.0001). Chemoprophylaxis was associated with a significantly lower EBV viral load (P < 0.001). Type or intensity of immunosuppressive therapy did not influence the occurrence of EBV primary infection or the level/persistence of EBV viral load. Chemoprophylaxis with VGCV/GCV is associated with a reduced incidence of EBV viremia in high-risk pediatric kidney allograft recipients in the first year post-transplant. (ClinicalTrials.gov number: NCT00963248).

Topics: Adult; Antiviral Agents; Chemoprevention; Child; Cohort Studies; Epstein-Barr Virus Infections; Female; Ganciclovir; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphoproliferative Disorders; Male; Pediatrics; Prospective Studies; Valganciclovir

A 35-year-old female was diagnosed with a primary central nervous system posttransplant Epstein-Barr-virus-associated lymphoproliferative disorder three years after a renal transplantation. The histological diagnosis of the brain tumour was a diffuse large B-cell lymphoma. The patient had had diabetes mellitus for 28 years and was treated with four weekly doses of the monoclonal antibody rituximab, the antiviral drug ganciclovir and high-dose prednisolone, and the immune suppression was reduced. After four weeks of treatment, a control magnetic resonance image showed complete regression of the central nervous system lesion.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antiviral Agents; Brain Neoplasms; Drug Therapy, Combination; Epstein-Barr Virus Infections; Female; Ganciclovir; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphoma, Large B-Cell, Diffuse; Prednisolone; Rituximab; Treatment Outcome; Valganciclovir

Preemptive therapy with ganciclovir has been recommended in the pediatric liver transplant strategy to avoid the development of posttransplant lymphoproliferative disorder (PTLD) from an high Epstein-Barr virus (EBV) is detected. We sought viral load to analyze the response to preemptive therapy with valganciclovir (VGC) in children with liver transplantations and an high quantitative EBV-PCR.. From June 2005 to December 2007, we tested 979 EBV-PCR among 80 pediatric liver transplant recipients, from those 21/80 PCR were tested from the date of transplantation and 59/80 belonged to the historical cohort (7/59 had a prior history of PTLD). Patients were divided into 2 groups depending upon whether they did (n = 22) or did not (n = 19) receive VGC treatment. The response to VGC was considered complete, if the PCR was negative at 30 and 60 days of treatment; and partial, when the PCR decreased at least 50%. Ganciclovir blood levels tested in 109 cases instances and correlated with the EBV-PCR.. A total of 369 (33%) positive PCR were detected in 36/80 patients (mean, 75,000 copies; range = 5000-4,200,000). Among the 22 episodes treated for 30 days, 34% showed complete responses, 41%, partial, and 23%, no response. Among the non-treated group the rates were 6%, 25%, and 68%, respectively (P = .01). However, no differences were observed among those episodes treated for 60 days. At the administered doses, hardly any patient reached the recommended ganciclovir therapeutic level at 2 hours (6 micro/mL). However, the mean PCR was lower when the ganciclovir levels were greater than 4 mg/L when compared with lower levels (P = .03).. After 30 days of treatment there was a response to VGC in the EBV viral load. There was high interpatient variability of ganciclovir serum concentrations, suggesting the need for pharmacokinetic monitoring to optimize treatment. There was a relationship between the concentration of ganciclovir and the EBV viral load.

Topics: Antiviral Agents; Child; Cohort Studies; Epstein-Barr Virus Infections; Ganciclovir; Genome, Viral; Herpesvirus 4, Human; Humans; Liver Transplantation; Polymerase Chain Reaction; Retrospective Studies; Valganciclovir; Viral Load

Topics: Antiviral Agents; Child; DNA, Viral; Epstein-Barr Virus Infections; Ganciclovir; Humans; Immunosuppression Therapy; Liver Transplantation; Lymphoproliferative Disorders; Valganciclovir

Epstein-Barr virus (EBV) infection after liver transplantation (LT) is associated with increased risk of posttransplant lymphoproliferative disorder (PTLD). Lowering immunosuppression is the current method to prevent PTLD in LT children with a high viral load. The aim of this study was to assess the efficacy and safety of valganciclovir (VGCV) in children with EBV infection after LT. Forty-seven children showing detectable EBV-DNA (72% asymptomatic) were treated with VGCV (520 mg/sqm twice daily) with no immunosuppression decrease (except in 4 cases). VGCV treatment started 17 months (median) after the onset of EBV infection. A 30-day treatment applied to 26 patients led to undetectable EBV-DNA in 11/32 courses (34.3%), with 82% relapsing. A long VGCV treatment (median: 8 months) achieved undetectable EBV-DNA in 20/42 (47.6%), 60% of whom maintained response off therapy. There were no new PTLD cases. Symptoms worsened in 1 (2.1%) in whom PTLD was suspected but not confirmed in liver and jejunum biopsies. Factors associated with achievement of undetectable EBV-DNA were a longer time from LT and a lower rate of intervening infections in comparison with nonresponders. The safety profile for VGCV was excellent. Graft rejection occurred in 6%. In conclusion, in 47 LT children with a sustained increased EBV load treated with VGCV and unchanged immunosuppression, PTLD was suspected in 1 child (2.1%). A viral load decrease could be achieved as EBV-DNA was undetectable in 47% of patients under prolonged treatment.

Topics: Antiviral Agents; Child; Child, Preschool; DNA, Viral; Epstein-Barr Virus Infections; Ganciclovir; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Infant; Kidney Function Tests; Liver Diseases; Liver Transplantation; Lymphoproliferative Disorders; Respiratory Tract Infections; Valganciclovir; Virus Replication