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Liver Transplantation : Official... Dec 2012Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of... (Meta-Analysis)
Meta-Analysis Review
Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients.
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Administration Schedule; Ganciclovir; Humans; Leukopenia; Liver Transplantation; Middle Aged; Odds Ratio; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir
PubMed: 22887929
DOI: 10.1002/lt.23530 -
Reviews in Medical Virology Nov 2014Human cytomegalovirus is the leading non-genetic cause of congenital malformation in developed countries. Congenital CMV may result in fetal and neonatal death or... (Review)
Review
Human cytomegalovirus is the leading non-genetic cause of congenital malformation in developed countries. Congenital CMV may result in fetal and neonatal death or development of serious clinical sequelae. In this review, we identified evidence-based interventions for prevention of congenital CMV at the primary level (prevention of maternal infection), secondary level (risk reduction of fetal infection and disease) and tertiary level (risk reduction of infected neonates being affected by CMV). A systematic review of existing literature revealed 24 eligible studies that met the inclusion criteria. Prevention of maternal infection using hygiene and behavioural interventions reduced maternal seroconversion rates during pregnancy. However, evidence suggested maternal adherence to education on preventative behaviours was a limiting factor. Treatment of maternal CMV infection with hyperimmune globulin (HIG) showed some evidence for efficacy in prevention of fetal infection and fetal/neonatal morbidity with a reasonable safety profile. However, more robust clinical evidence is required before HIG therapy can be routinely recommended. Limited evidence also existed for the safety and efficacy of established CMV antivirals (valaciclovir, ganciclovir and valganciclovir) to treat neonatal consequences of CMV infection, but toxicity and lack of randomised clinical trial data remain major issues. In the absence of a licensed CMV vaccine or robust clinical evidence for anti-CMV therapeutics, patient education and behavioural interventions that emphasise adherence remain the best preventative strategies for congenital CMV. There is a strong need for further data on the use of HIG and other antivirals in pregnancy, as well as the development of less toxic, novel, antiviral agents.
Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious
PubMed: 25316174
DOI: 10.1002/rmv.1814 -
Transplant International : Official... Dec 2021Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral-agents are used as universal prophylaxis. Our purpose aimed to compare and rank... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of conventional antiviral agents in preventive strategies for cytomegalovirus infection after kidney transplantation: a systematic review and network meta-analysis.
Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral-agents are used as universal prophylaxis. Our purpose aimed to compare and rank efficacy and safety. MEDLINE, Embase, SCOPUS, and CENTRAL were used from inception to September 2020 regardless language restriction. We included randomized clinical trials (RCTs) comparing the CMV infection/disease prophylaxis among antiviral-agents in adult KT recipients. Of 24 eligible RCTs, prophylactic valganciclovir (VGC) could significantly lower the overall CMV infection and disease risks than placebo with pooled risk differences (RDs) [95% confidence interval (CI)] of -0.36 (-0.54, -0.18) and -0.28 (-0.48, -0.08), respectively. Valacyclovir (VAC) and ganciclovir (GC) significantly decreased risks with the corresponding RDs of -0.25 (-0.32, -0.19) and -0.30 (-0.37, -0.22) for CMV infection and -0.26 (-0.40, -0.12) and -0.22 (-0.31, -0.12) for CMV disease. For subgroup analysis by seropositive-donor and seronegative-recipient (D+/R-), VGC and GC significantly lowered the risk of CMV infection/disease with RDs of -0.42 (-0.84, -0.01) and -0.35 (-0.60, -0.12). For pre-emptive strategies, GC lowered the incidence of CMV disease significantly with pooled RDs of -0.33 (-0.47, -0.19). VGC may be the best in prophylaxis of CMV infection/disease follow by GC. VAC might be an alternative where VGC and GC are not available.
Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Network Meta-Analysis
PubMed: 34580930
DOI: 10.1111/tri.14122 -
Transplant Infectious Disease : An... Apr 2021Kidney transplant recipients (KTRs) have increased risk for cytomegalovirus (CMV) infection/disease given the necessity of drug-induced immunosuppression. A... (Review)
Review
Kidney transplant recipients (KTRs) have increased risk for cytomegalovirus (CMV) infection/disease given the necessity of drug-induced immunosuppression. A comprehensive review of published literature reporting real-world data on prevention strategies utilized and associated CMV burden outcomes is limited. Such data could help inform future clinical practice and identify unmet needs in CMV management. We conducted a systematic review of observational studies published in Medline or EMBASE from January 2008 to November 2018 to identify current real-world CMV management approaches, CMV infection/disease risk factors, and outcomes associated with CMV infection. Descriptive statistics and pooled quantitative analyses were conducted. From 1608 records screened, 86 citations, including 69 803 adult KTR, were included. Prophylaxis and preemptive therapy (PET) were predominant approaches among D+/R- and R + CMV serostatus transplants, respectively. Valganciclovir and ganciclovir were frequently utilized across CMV risk strata. Despite prevention approaches, approximately one-fourth of KTR developed CMV infection. Age and D+/R- CMV serostatus were consistent risk factors for CMV infection/disease. CMV infection/disease was associated with increased mortality and graft loss. CMV was similarly associated with acute rejection (AR) risk, but with high heterogeneity among studies. Limited data were available on CMV and opportunistic infections (OIs) risk. CMV remains a significant issue. New strategies may be needed to optimize CMV management.
Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Risk Factors; Transplant Recipients; Valganciclovir
PubMed: 33012092
DOI: 10.1111/tid.13483 -
American Journal of Transplantation :... Feb 2015We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing... (Comparative Study)
Comparative Study Meta-Analysis Review
We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing cytomegalovirus (CMV) disease (CMD) among liver transplant recipients (LTRs). We performed an electronic search of MEDLINE, EMBASE and the Cochrane Database till December 2013. Studies that assessed UP or PE for preventing CMD in LTRs were included. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was CMD, secondary outcomes being acute cellular rejection (ACR), graft loss (GL) and mortality. Due to the heterogeneity of comparative studies, an indirect comparison was performed. Pooled incidence rates with 95% confidence interval (CI) are calculated for each outcome using a random-effects model. Thirty-two studies involving 2456 LTRs were included. The majority of the studies were of low risk of bias. Irrespective of donor/recipient CMV sero-status, CMD was 10% with UP (95% CI: 6-14; I(2) = 87%; 16 studies, n = 1581) and 7% with PE (95% CI: 3-10; I(2) = 84%; 16 studies, n = 875) (mean difference 2.6; 95% CI: -3.25 to 8.45, p = 0.34). Likewise, ACR and mortality were similar with the two strategies. However, GL was significantly lower in the UP group, regardless of donor/recipient sero-status. In indirect comparison, the incidence of CMD, ACR and mortality in LTRs were similar with two strategies. Trials comparing the two strategies directly are needed.
Topics: Adult; Aged; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Humans; Incidence; Liver Diseases; Liver Transplantation; Male; Middle Aged; Risk Assessment; Survival Rate; Valganciclovir
PubMed: 25522141
DOI: 10.1111/ajt.13044 -
Transplant Infectious Disease : An... Feb 2023Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs)....
BACKGROUND
Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT.
METHODS
We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs.
RESULTS
Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/μl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/μl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N.
CONCLUSION
Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.
Topics: Humans; Adult; Kidney Transplantation; Neutropenia; Leukopenia; Valganciclovir; Immunosuppressive Agents; Granulocyte Colony-Stimulating Factor; Mycophenolic Acid; Anemia; Opportunistic Infections; Transplant Recipients; Graft Rejection
PubMed: 36508475
DOI: 10.1111/tid.14000 -
The Laryngoscope Nov 2022To search for existing evidence of a beneficial effect of (val)ganciclovir on hearing in children with congenital cytomegalovirus (cCMV) infection and to identify future... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To search for existing evidence of a beneficial effect of (val)ganciclovir on hearing in children with congenital cytomegalovirus (cCMV) infection and to identify future research questions.
STUDY DESIGN
Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searches were performed in PUBMED, EMBASE, and WEB OF SCIENCE on December 15, 2021.
METHODS
Studies providing ear-specific hearing results after treating children with cCMV-related hearing loss with (val)ganciclovir were retained. A meta-analysis [Peto odds ratio (OR), Review Manager 5.3] was performed to compare hearing outcome between treated and untreated children. The National Institutes of Health tool was used for quality assessment and heterogeneity was assessed with I statistics.
RESULTS
Eighteen studies with a total of 682 treated patients were included for the systematic review. Our meta-analysis showed that treating symptomatic children with hearing loss resulted in more hearing improvement [Peto OR 7.72, 95% confidence interval (CI) 3.08-19.34] and less hearing deterioration (Peto OR 0.23, 95% CI 0.10-0.57). Relative to an improvement and deterioration rate of 9.4% and 28.2% in an untreated group, the rate of the treated group was 44.5% and 6.3%, respectively.
CONCLUSIONS
There is sufficient evidence in literature to support treatment with (val)ganciclovir of children with symptomatic cCMV and hearing loss. However, still today, there is insufficient evidence of the potential beneficial role of (val)ganciclovir on hearing outcome of children with isolated hearing loss, late-onset hearing loss, and asymptomatic cCMV. The urgent need for future prospective, randomized clinical trials still exists. A standardization of definitions and treatment protocols would create uniformity in future studies. Laryngoscope, 132:2241-2250, 2022.
Topics: Antiviral Agents; Child; Cytomegalovirus; Cytomegalovirus Infections; Deafness; Ganciclovir; Hearing; Hearing Loss; Hearing Loss, Sensorineural; Humans
PubMed: 35072277
DOI: 10.1002/lary.30027 -
Polski Merkuriusz Lekarski : Organ... Jul 2013Cytomegalovirus infection is particularly dangerous for patients undergoing solid organs transplantation. Among these patients cytomegalovirus disease (CMV) may occur.... (Review)
Review
UNLABELLED
Cytomegalovirus infection is particularly dangerous for patients undergoing solid organs transplantation. Among these patients cytomegalovirus disease (CMV) may occur. CMV disease is associated with increased mortality, organ damage and reduced graft survival. THE AIM OF THE STUDY was to determine the clinical outcomes (clinical efficacy and safety profile) for the use of valganciclovir administered for 200 days compared to standard period of 100 days in the prevention of cytomegalovirus disease in seronegative patients after kidney transplantation from infected donor (high risk patients).
MATERIAL AND METHODS
A systematic review of literature published during the period: 1st January 1966-31st October 2010, was performed in order to assess the efficacy and safety of valganciclovir in the treatment of cytomegalovirus disease. Databases MEDLINE (PubMed), EMBASE and Cochrane were searched.
RESULTS
A systematic review yielded 1 randomized and 3 nonrandomized clinical trials. 200 days prophylaxis with valganciclovir significantly decreased a risk of: cytomegalovirus disease, CMV viral load, opportunistic infections; percentage of patients with high viral load was also significantly decreased compared to 100 days therapy. The safety profile of extended therapy was similar to that observed within 100 days prophylaxis. The higher risk of leucopenia in the 200 days than 100 days group was the only one adverse event that met statistical significance. The results of non-randomized trials were comparable to those mentioned above.
CONCLUSION
Prolonged prophylaxis of cytomegalovirus till 200 days in high-risk patients (D+/B-) is safe and provides significant therapeutic benefits.
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Administration Schedule; Ganciclovir; Graft Survival; Humans; Kidney Transplantation; Treatment Outcome; Valganciclovir; Viral Load
PubMed: 23984598
DOI: No ID Found -
Medical Microbiology and Immunology Oct 2017Congenital cytomegalovirus (CMV) infection is the leading cause for sensorineural hearing loss and mental retardation in children without genetic diseases worldwide.... (Review)
Review
Congenital cytomegalovirus (CMV) infection is the leading cause for sensorineural hearing loss and mental retardation in children without genetic diseases worldwide. There is little evidence guiding therapeutic strategies during pregnancy when intrauterine fetal CMV infection is confirmed. We provide a systematic review of the use of ganciclovir (GCV) or VGCV during pregnancy discussing safety of its use for mother and fetus and describe two cases of intrauterine therapy of fetal CMV infection with valganciclovir (VGCV). A PubMed database search was done up to November 16, 2016 without any restrictions of publication date or journal, using the following keywords: "valganciclovir" or "ganciclovir" and "pregnan*". Furthermore, citations were searched and expert references were obtained. Reported cases were considered if therapy was in humans and initiation of treatment of the CMV infection was during pregnancy. In total, seven case reports were retrieved which described GCV or VGCV use during pregnancy for fetal or maternal CMV infection. In the four cases of treatment for maternal CMV infection, no negative effects on the fetus were reported. Three cases of GCV administration to pregnant woman with the intention of fetal treatment after proven fetal infection were found. We additionally present two cases of VGCV treatment in pregnancy from our center of tertiary care. VGCV seems to be a safe treatment for congenital CMV infection for the mother and the fetus. Therapeutic concentrations can be achieved in the fetus by oral intake of the mother and CMV replication can be suppressed. Larger studies are needed to evaluate this therapeutic intervention and the long-term effects.
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug-Related Side Effects and Adverse Reactions; Female; Fetal Diseases; Ganciclovir; Humans; Pregnancy; Pregnancy Complications, Infectious; Treatment Outcome; Valganciclovir
PubMed: 28733760
DOI: 10.1007/s00430-017-0512-3 -
Clinical Transplantation Jan 2024Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients... (Review)
Review
BACKGROUND
Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID).
METHODS
We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs.
RESULTS
Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3).
CONCLUSIONS
The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.
Topics: Humans; Kidney Transplantation; Cytomegalovirus; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Gastrointestinal Diseases
PubMed: 38063324
DOI: 10.1111/ctr.15218