Evidence Of Cytomegalovirus Infection Research Articles

Apoptosis, Crypt Dropout, and Equivocal Immunohistochemical Staining May Indicate Cytomegalovirus Infection in Inflammatory Bowel Disease Patients.

Cytomegalovirus (CMV) colitis superimposed on inflammatory bowel disease (IBD) can be challenging to diagnose. This study aimed to determine what histologic clues and immunohistochemistry (IHC) utilization practices, if any, can help diagnose CMV superinfection in IBD. Colon biopsies were reviewed from all patients with CMV colitis with and without IBD between 2010 and 2021 at one institution, along with a separate cohort of IBD patients with negative CMV IHC. Biopsies were assessed for histologic features of activity and chronicity, phlebitis, fibrin thrombi, basal crypt apoptosis, CMV viral cytopathic effect (VCE), and CMV IHC positivity. Features between groups were compared, with statistical significance set at P -value <0.05. The study included 251 biopsies from 143 cases (21 CMV-only, 44 CMV+IBD, 78 IBD-only). Compared with the IBD-only group, the CMV+IBD group was more likely to show apoptotic bodies (83% vs. 64%, P =0.035) and crypt dropout (75% vs. 55%, P =0.045). CMV was detected by IHC in 18 CMV+IBD cases without VCE on hematoxylin and eosin (41%). In the 23 CMV+IBD cases where IHC was performed on all concurrent biopsies, IHC was positive in at least 1 biopsy in 22 cases. Six individual CMV+IBD biopsies with no VCE on hematoxylin and eosin demonstrated equivocal IHC staining. Of these, 5 had evidence of CMV infection. IBD patients with superimposed CMV infection are more likely to demonstrate apoptotic bodies and crypt dropout compared with their noninfected counterparts. Equivocal IHC staining for CMV may indicate true infection in IBD patients, and staining multiple biopsies from the same accession can improve CMV detection.

Impact of maternal cytomegalovirus seroconversion on newborn and childhood hearing loss.

Objectives/hypothesisThe objective of this study is to describe long‐term hearing outcomes in infants born to mothers with a known cytomegalovirus (CMV) positivity who were not tested for congenital CMV. Study typeClinical research study.DesignRetrospective cohort study.MethodsRetrospective chart review was performed for mothers seropositive to CMV. Mother–infant dyads (130) were identified between January 1, 2013 and January 1, 2017. Outcomes data was collected through June 1, 2020. Demographics, risk factors for hearing loss, evidence of CMV infection, other causes of hearing loss, need for speech therapy services, and results of all hearing tests were collected.ResultsAll 130 infants were asymptomatic and 5 were tested for congenital CMV. Five were negative for CMV and excluded from analyses. Of the remaining 125, only 1 had low‐viral avidity IgG antibodies. None had IgM antibodies. Four children (3.2%) had hearing loss at last audiogram and one child had delayed onset SNHL due to an enlarged vestibular aqueduct. Speech therapy for communication was required for 33 children (26.4%).ConclusionsKnowledge of maternal perinatal CMV status can allow for education about possible sequelae of cCMV, as well as trigger an alert for testing babies born to mothers with low‐viral avidity IgG during the first trimester, when the risk of vertical transmission is highest. Also, babies born to CMV positive mothers may be more at risk for communication delays necessitating intervention. Studies focusing on the impact of maternal CMV related to childhood communication deficits could elucidate any direct relationships.

Comparison of Outcomes in Heart Transplant Recipients Receiving CMV Prophylaxis with CMV IVIG with Valganciclovir versus Valganciclovir Alone

<h3>Purpose</h3> Cytomegalovirus (CMV) remains one of the most common opportunistic infections affecting orthotopic heart transplant (OHT) patients, with seronegative (R-) recipients receiving transplants from seropositive donors (D+) being at the highest risk. CMV intravenous immune globulin (CMV IVIG) use for prophylaxis has been limited since the release of valganciclovir (VGC) due to efficacy, infusion-related toxicities, and cost. The ISHLT guidelines for the care of heart transplant recipients state there may be a role for CMV IVIG in high risk (D+/R-) OHT in combination with VGC, but it is not clearly defined. The goal of this study is to evaluate if adding CMV IVIG to VGC impacts the rates of CMV infection. <h3>Methods</h3> This is a retrospective, pre-post study of CMV high risk adult OHT recipients transplanted between 1/1/2015-12/31/2018 (n=51). In 9/2017, the institutional protocol for prophylaxis of high risk CMV OHT recipients changed. Previously, high risk patients were given CMV IVIG for 3 months in addition to VGC 900 mg daily for 6 months (or renal dose equivalent). After the protocol change, patients received VGC alone for 6 months. CMV infection was defined as evidence of CMV replication regardless of symptoms. CMV disease was defined as evidence of CMV infection with attributable symptoms. <h3>Results</h3> Of the CMV high risk OHT recipients, 29 received CMV IVIG+VGC and 22 received VGC alone. There were no differences in baseline characteristics, immunosuppressive regimens, renal function, or VGC dosing between cohorts (Table 1). There was no difference in the rates of CMV infection at 1 year between cohorts (34.5% vs. 18.2%; p=0.225). Furthermore, there was no difference in rates of CMV pneumonia (6.9% vs 0%, p=0.499) or CMV colitis (0% vs 4.5%, p=0.431) between cohorts. Overall, only one patient had breakthrough CMV and that patient was on VGC therapy alone. <h3>Conclusion</h3> CMV IVIG appears to have no added benefit in preventing CMV infections in the era of VGC therapy.

Valganciclovir-Ganciclovir Use and Systematic Therapeutic Drug Monitoring. An Invitation to Antiviral Stewardship.

Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations.

Comparison of Outcomes in Heart Transplant Recipients Receiving CMV Prophylaxis with CMV IVIG with Valganciclovir versus Valganciclovir Alone

Cytomegalovirus (CMV) remains one of the most common opportunistic infections affecting orthotopic heart transplant (OHT) patients, with seronegative (R-) recipients receiving transplants from seropositive donors (D+) being at the highest risk. CMV intravenous immune globulin (CMV IVIG) use for prophylaxis has been limited since the release of valganciclovir (VGC) due to efficacy, infusion-related toxicities, and cost. The ISHLT guidelines for the care of heart transplant recipients state there may be a role for CMV IVIG in high risk (D+/R-) OHT in combination with VCG, but it is not clearly defined. The goal of this study is to evaluate if adding CMV IVIG to VGC impacts the rates of CMV infection. This is a retrospective, pre-post study of CMV high risk adult OHT recipients transplanted between 1/1/2015-12/31/2018 (n=51). In 9/2017, the institutional protocol for prophylaxis of high risk CMV OHT recipients changed. Previously, high risk patients were given CMV IVIG for 3 months in addition to VGC 900 mg daily for 6 months (or renal dose equivalent). After the protocol change, patients received VGC alone for 6 months. CMV infection was defined as evidence of CMV replication regardless of symptoms. CMV disease was defined as evidence of CMV infection with attributable symptoms. Of the CMV high risk OHT recipients, 29 received CMV IVIG+VGC and 22 received VGC alone. There were no differences in baseline characteristics, immunosuppressive regimens, renal function, or VGC dosing between cohorts (Table 1). There was no difference in the rates of CMV infection at 1 year between cohorts (34.5% vs. 18.2%; p=0.225). Furthermore, there was no difference in rates of CMV pneumonia (6.9% vs 0%, p=0.499) or CMV colitis (0% vs 4.5%, p=0.431) between cohorts. Overall, only one patient had breakthrough CMV and that patient was on VGC therapy alone. CMV IVIG appears to have no added benefit in preventing CMV infections in the era of VGC therapy.

Cytomegalovirus hepatitis after bone marrow transplantation: An autopsy study with clinical, histologic and laboratory correlates.

Mortality from cytomegalovirus disease after marrow transplantation can be reduced by treatment with antiviral drugs based on the detection of viremia and organ involvement. We examined autopsy liver specimens to determine the frequency, extent and outcome of cytomegalovirus hepatitis and whether cytomegalovirus hepatitis occurred in the absence of cytomegalovirus disease elsewhere. Autopsy specimens from 50 transplant patients were evaluated for cytomegalovirus-infected cells, in five groups of 10, according to extent of CMV during life and at autopsy. Liver sections were examined by routine light microscopy, immunohistochemistry and in situ DNA hybridization. Clinical and laboratory data collected during the last 30days of life were analysed as markers of liver cytomegalovirus infection. Cytomegalovirus-infected cells were detected in the livers of 10/10 patients with cytomegalovirus infection during life and widespread cytomegalovirus at autopsy; in 3/20 livers from patients with cytomegalovirus infection during life but negative liver cultures at autopsy; and in 1/10 livers from cytomegalovirus-seropositive patients who had been without other evidence of cytomegalovirus infection. Histology detected a lower density of cytomegalovirus-bearing cells per unit area of liver, compared to immunohistochemistry and in situ hybridization. No cytomegalovirus-infected cells were detected in livers from cytomegalovirus-seronegative controls. No distinctive clinical or laboratory findings correlated with liver cytomegalovirus detection. CMV liver disease is common in allografted patients with disseminated CMV but may rarely be isolated to the liver, best demonstrated with IHC and ISH. Massive hepatic necrosis from CMV was not seen in any autopsy liver in this study.

T-cell mitochondrial dysfunction and lymphopenia in DOCK2-deficient patients

This study delineates the mitochondrial defects in DOCK2-deficient T cells contributing to the T cell lymphopenia characteristic of this primary immunodeficiency.

Human Cytomegalovirus Infection is Associated with Essential Hypertension in Kazakh and Han Chinese Populations

BackgroundWe aimed to study the association between cytomegalovirus (CMV) infection and hypertension in Kazakh and Han populations from Xinjiang Province, China.Material/MethodsWe analyzed data on 800 Kazakhs (467 hypertension patients and 333 healthy control participants) and 800 Hans (482 hypertension patients and 318 healthy control participants) aged 18–84 years old. ELISA and real-time quantitative PCR coupled with restriction fragment length polymorphism analysis were applied for determining CMV infection and glycoprotein B (gB) genotypes, respectively.ResultsSerologic evidence of CMV infection was obtained for 95.4% and 90.1% of the Kazakhs and Hans, respectively. The CMV seroprevalence rates among the Kazakh and Han participants with hypertension were 96.8% and 89.8%, respectively. Multiple logistic regression analyses revealed statistically significant independent associations between CMV seropositivity and hypertension in Kazakh males and between CMV antibody titers and hypertension in Hans; significant relationships also existed between CMV antibody titers and blood pressure in Hans. In Kazakhs, 3 CMV gB genotypes were identified: gB2 and genotype mixtures gB1+gB2 and gB2+gB3. In Hans, 4 CMV gB genotypes were identified: gB1, gB2, gB1+gB2, and gB2+gB3. Of the 4 studied genotypes, gB2+gB3 showed a significant independent association with hypertension in Kazakh females.ConclusionsCMV infection is associated with essential hypertension in Kazakh males and Hans in Xinjiang. CMV seropositivity is associated with hypertension in Kazakh males, and CMV antibody titers are associated with blood pressure and hypertension in Han males and females. Moreover, the CMV gB2+gB3 genotype mixture is associated independently with essential hypertension in Kazakh females.

Bendamustine plus alemtuzumab is safe and feasible treatment for fludarabine refractory chronic lymphocytic leukaemia (CLL)

Bendamustine plus alemtuzumab is safe and feasible treatment for fludarabine refractory chronic lymphocytic leukaemia (<scp>CLL</scp>)

Cytomegalovirus in hematological malignancies

Cytomegalovirus (CMV) infection frequently causes cytopenia in hematopoietic stem cell transplant setting where there are clear cut recommendations for prophylaxis, screening and pre-emptive treatment of CMV infection [1]. However, evidence of CMV infection in hematological malignancies other than stem cell transplant setting is lacking. A retrospective, single centre study of autopsied patients of acute leukemia, chronic leukemia or myelodysplastic syndrome (without stem cell transplant), reported a low, but rising prevalence of CMV pneumonitis over a 5-year period, with a case fatality rate of 57% [2]. Kanvinde, et al. [3] describe 13 episodes of CMV in 11 cases of hematological malignancy, which were treated with intravenous gancyclovir. These cases were diagnosed based on detection of antigen or DNA, of which, nearly half were diagnosed by a qualitative PCR which is not the standard method for diagnosing CMV infection. Further, none of these cases had demonstration of virus by culture or histopathology. Few of these episodes were associated with other documented viral or bacterial infections which by themselves are known to cause prolonged cytopenias. Further, two of these patients had resolution of their symptoms even before initiation of gancyclovir. It would be reasonable to state that these patients may have had evidence of CMV infection but certainly CMV disease was not demonstrated in any case, and thus none of these patients can be attributed to have CMV-related cytopenia.

Acyclovir prophylaxis against cytomegalovirus in high risk paediatric kidney transplant recipients

Aims Cytomegalovirus (CMV) is an important infectious pathogen after kidney transplantation causing significant morbidity and mortality. Several prophylactic antiviral treatments are used and the aim of this study was to review the efficacy of acyclovir prophylaxis to prevent CMV infection in paediatric kidney transplant recipients. Methods The clinical records of kidney transplant recipients over a 20 year period were reviewed. Details of recipient and donor CMV serostatus were recorded together with information regarding prophylaxis received, evidence of CMV infection, and CMV related complications. All patients were scheduled to receive 5 mg/kg loading dose acyclovir peri-operatively and then acyclovir 200 mg qds for 90 days. Results 192 kidney transplants were performed in 177 children between 1991 and 2010. Only first grafts were considered in subsequent analysis. 36 recipients were identified as being at risk of CMV after transplant (i.e. recipient CMV IgG negative, donor CMV IgG positive). All of these patients received oral acyclovir prophylaxis and 58% received an intravenous loading dose. Of these 36 patients, 9 (25%) developed CMV viraemia with a positive CMV PCR. 7 patients met the criteria for CMV disease. 8 of the 9 patients developed viraemia whilst on acyclovir indicating active CMV replication despite treatment. There were no cases of severe infection or tissue invasive disease. There was no graft loss as a consequence of CMV infection. Conclusions The evidence supporting the choice of prophylactic treatment for CMV in paediatric kidney transplant recipients is limited. Recent data from the adult population indicate rates of disease are substantially lower in kidney transplant recipients treated with valganciclovir. These data indicate that in high risk individuals there is substantial risk of CMV disease despite prophylaxis with acyclovir and suggest that prophylaxis with valganciclovir is likely to result in significantly lower rates of CMV disease.

Pre and Post Transplant Cytomegalovirus (CMV) Infection and Successful Graft Survival

Allograft rejection continues to be a major problem and is the leading cause of graft loss in renal transplant recipients. Histocompatibility testing plays an important role in selection of donors for transplantation. A correct assignment of HLA antigens is considered important given that inadequate HLA matching of patient-donor pairs is associated with rejection in kidney transplantation. The present study was to assess a long and successful graft survival in end stage renal failure patients. 50 live related renal transplant patient-donor pairs were selected at random (n=100). Serological HLA A, B and DR typing results were compared to typing results obtained using sequence-specific primers in the polymerase chain reaction. Evidence of CMV infection was also monitored by CMV-PCR and CMV antigenemia pp65 assay on all patients and compared with the occurrence of acute rejection in the post transplant period. 4 patients developed CMV disease with graft dysfunction, during the first 12 weeks post-transplantation, which responded to specific anti-viral therapy and reduction in immunosuppression. Our results reveal that Frequent monitoring of CMV-PCR or CMV pp65 antigenemia and prompt start of treatment in such patients is required. Early diagnosis of CMV antigenemia improves graft and patient survival.

The Prevalence and Efficacy of Ganciclovir on Steroid-refractory Ulcerative Colitis With Cytomegalovirus Infection

It remains controversial whether or not cytomegalovirus infection in patients with active ulcerative colitis reflects a nonpathogenic colonization or a pathogenic disease warranting antiviral therapy. The aim of this study was to determine the prevalence of cytomegalovirus infection in patients with active ulcerative colitis and the therapeutic efficacy of ganciclovir against cytomegalovirus infection in patients with steroid-refractory ulcerative colitis. A prospective, multicenter study was conducted in 72 patients with moderate-to-severe ulcerative colitis who were treated with intravenous steroids. The presence of cytomegalovirus was evaluated serologically and histopathologic examination, including immunohistochemical staining. In patients with steroid-refractory ulcerative colitis, cytomegalovirus infections were treated with intravenous ganciclovir. In patients with steroid-responsive ulcerative colitis, steroid therapy was continued irrespective of cytomegalovirus infection. The evidence of cytomegalovirus infection was found in 31 patients (43%) with moderate-to-severe active ulcerative colitis. In patients with steroid-refractory ulcerative colitis, the cytomegalovirus infection rate increased to 67% (14 of 21). No significant clinical and endoscopic differences existed between patients with and without a cytomegalovirus infection; however, the amount of steroids used during the flare-up period was significantly higher in patients with a cytomegalovirus infection (P = 0.013). Eleven of 14 patients (79%) with steroid-refractory ulcerative colitis and a cytomegalovirus infection improved with ganciclovir treatment. Cytomegalovirus infections in the steroid-responsive group (17 of 31) did not require ganciclovir therapy. Cytomegalovirus infections are frequently observed in patients with moderate-to-severe ulcerative colitis, especially steroid-refractory ulcerative colitis. Ganciclovir was effective in patients with steroid-refractory ulcerative colitis who had a cytomegalovirus infection.

Successful Use of Fecal Bacteriotherapy in Severe Crohnʼs Colitis and Refractory Clostridium difficile Infection

Purpose: Fecal bacteriotherapy has been used to treat refractory Clostridium difficile infection, predominantly in an outpatient setting. We describe a patient with severe Crohn's colitis requiring hospitalization in whom fecal bacteriotherapy was successfully used to treat her refractory Clostridium difficile infection. Case: A 33-year-old female with history of Crohn's colitis on azithioprine and adalimumab was admitted with severe abdominal pain, hematochezia, and fever. One month prior to admission, the patient reported frequent bowel movements, abdominal pain and hematochezia. A Clostridium difficile PCR test was positive. Despite two courses of oral vancomycin, her symptoms persisted along with worsening fever, and the patient was subsequently hospitalized. Intravenous metronidazole and vancomycin enemas were started; oral vancomycin was continued. A flexible sigmoidoscopy revealed extensive pseudomembranes. Colonic biopsies revealed severe chronic active colitis but no evidence of cytomegalovirus infection. One dose of IVIG (400 mg/kg) was given on Hospital Day (HD) 3 without clinical improvement. The patient elected to proceed with fecal bacteriotherapy as a potential salvage therapy prior to colectomy. Her husband was screened for HIV and Hepatitis A, B, and C, and his stool was screened for Clostridium difficile, enteric stool pathogens, and ova and parasites. Seventyfive grams of donor stool was emulsified with 200mL normal saline and administered to the patient through a nasogastric tube on HD 10. Over the next several days, the patient's bowel movements became less frequent, and her abdominal pain improved. Two days after stool transfer, a repeat Clostridium difficile PCR test was negative. Over the next week, the patient was started on methylprednisolone and infliximab. The patient's abdominal pain markedly improved, and her hematochezia resolved. The patient was discharged home on HD 23. Discussion: Fecal bacteriotherapy is thought to work by re-establishing essential anerobes and restoring imbalances in stool composition and metabolism. There is a paucity of data in the use of fecal bacteriotherapy in patients with refractory Clostridium difficile infection in the setting of severe Crohn's colitis. In our patient, fecal bacteriotherapy appears to have resolved the Clostridium difficile infection without consequences. After resolving her Clostridium difficile infection, we could then address the patient's underlying Crohn's disease with immunosuppressive therapy. This case suggests a potential role of fecal bacteriotherapy in treating patients with Clostridium difficile infection refractory to traditional therapies who have concomitant severe inflammatory bowel disease.

Low frequency of cytomegalovirus infection during exacerbations of inflammatory bowel diseases

Although numerous reports have described inflammatory bowel diseases (IBDs) complicated with cytomegalovirus (CMV) infection, the virus participation as an exacerbating factor remains unclear. The aim of this study was thus to clarify the clinical significance of CMV infection complicating exacerbation and to correlate CMV detection with various characteristics in IBD patients. Sixty-seven colonic biopsies obtained from 53 patients admitted for IBD exacerbation were retrospectively analyzed by real-time PCR assay. The CMV genome was detected in seven (10.4%) colonic biopsies related to seven patients (three ulcerative colitis and four Crohn's diseases). Among the patients with IBD studied, patients with evidence of CMV infection were older (P = 0.047), were more likely male gender (relative risk [RR] 4.48; 95% confidence interval [CI] 0.94-21.36), received corticosteroids (RR 3.2; CI 0.79-13.02) or azathioprine (RR 3.17; CI 0.80-12.57) treatments, presented more extended lesions (RR for rectum-sigmoid-left colon 3.75 (0.0-69.37) and for pancolitis 2.45 (0.36-16.23)), and had a more severe disease (RR 3.3; CI 0.87-12.48) than those without CMV infection. Viral loads measured in the colonic mucosa of infected patient ranged from 5 to 236961 genome copies by microgram of total extracted DNA. No relationship was observed between the severity of the disease and the viral load level. Furthermore, CMV disappeared in five infected IBD patients in remission without antiviral agents. In conclusion, these results showed infrequent CMV detection in colonic biopsies of IBD patients during exacerbation leaving open the question of the relationship between CMV reactivation and the onset or the severity of IBD exacerbation.

A case of ABO‐incompatible renal transplantation with smoldering antibody‐mediated rejection that led to chronic vascular rejection 14 months after transplantation

Abstract: A 55‐year‐old female patient with chronic renal failure received an ABO‐incompatible secondary renal transplantation from her husband. She had positive pre‐operative flow panel reactive antibody reactivity to classes I and II. Donor‐specific antibody (DSA) was also positive in classes I and II. She was treated with rituximab, plasma exchange, and splenectomy before transplantation. The serum creatinine (sCr) level rose to 1.26 mg/dL on post‐operative day (POD) 17, and the episode graft biopsy specimen was diagnosed as mild acute vascular rejection. On POD 31, the protocol biopsy showed mild transplant glomerulitis and peritubular capillaritis (ptc2) with positive C4d, suggestive of antibody‐mediated rejection (AMR). She had cytomegalovirus (CMV) infection and was treated with ganciclovir. When the sCr rose to 1.7 mg/dL, two months post‐operatively, the episode biopsy showed mild AMR and no evidence of CMV infection. Since then, no clinical evidence of rejection has been observed, but protocol biopsy specimens obtained six and nine months postoperatively showed histologic findings suggestive of smoldering, persistent AMR. The patient was treated with deoxyspergualin and steroid pulse therapy after each protocol biopsy. Fourteen months after her operation, the protocol biopsy specimen revealed chronic allograft nephropathy with chronic rejection. It showed sclerosing vasculopathy with neomedia formation in the interlobular arteries and mild thickening of the peritubular capillary basement membrane with ptc1. DSA was not detected post‐operatively. With strategies using recently available immunosuppressive agents, the long‐term survival rate of renal grafts does not differ between ABO‐incompatible and ABO‐compatible cases. Anti‐human leukocyte antigen (HLA) antibody may have been the cause of smoldering AMR and consequent chronic rejection in this case. Further research is needed to devise a more successful desensitization regimen for organ transplantation in highly sensitized recipients.

A Safe Immunosuppressive Protocol in Adult-to-Adult Living Related Liver Transplantation

Background In this series of 32 adult-to-adult living related liver transplantations, we assessed the efficacy and safety of basiliximab in combination with a tacrolimus-based regimen. Basiliximab, a chimeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor (CD25), has been extensively evaluated as induction therapy for cadaveric liver transplant recipients. Patients and Methods Thirty-two adult-to-adult living related liver transplantations were performed in the last 3 years. All patients received two 20 mg doses of basiliximab (days 0 and 4 posttransplantation) followed by tacrolimus (0.15 mg/kg/d; 10–15 ng/mL target trough levels) and steroids (starting with 20 mg IV switched to PO as soon as the patient was able to eat and weaned within 1–2 months). The average follow-up was 395 days after transplantation. Results Of the patients, 93.75% remained rejection-free during follow-up with an actuarial rejection-free probability of 92.59% within 3 months. Two patients (6%) had one episode of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 86.85% and 81.25%. One patient (3%) experienced one episode of sepsis. There was no evidence of cytomegalovirus infections or side effects related to the basiliximab. We found zero de novo malignancy but we observed two patients with metastatic spread of their primary malignancy during the follow-up. Conclusion Basiliximab in association with tacrolimus and steroids is effective as prophylaxis of ACR among adult living related liver transplant recipients.

Management of cytomegalovirus infection by weekly surveillance after renal transplant: analysis of cost, rejection and renal function.

Recently published guidelines recommend anti-viral prophylaxis as the best method of preventing cytomegalovirus (CMV) disease in the post-transplant period, but some authors have suggested that surveillance strategies may be as effective and less costly. The aim of the present study was to analyse the effectiveness and cost of a deferred treatment strategy using weekly CMV polymerase chain reaction (PCR) surveillance in high risk renal transplant recipients. We used weekly surveillance for plasma CMV PCR positivity for the first 3 months in consecutive renal transplants between CMV seropositive donors and seronegative recipients, and analysed incidence of CMV infection, timing of infection, acute rejection and renal function at 1 year. There was evidence of CMV infection in 27/41 (65.9%) patients and of CMV disease in 20/41 (48.8%). Only 8/20 (40%) patients were PCR positive before disease onset. Patients were treated on the basis of clinical evidence of CMV disease (deferred strategy), but we used the data to compare the potential costs of a pre-emptive strategy (all patients PCR positive before the onset of clinical features of disease treated with intravenous ganciclovir) and prophylaxis (oral ganciclovir for 3 months in all patients). The deferred strategy cost pound 1159 per patient (excluding the cost of hospitalization) while a pre-emptive strategy would cost pound 1381 per patient. Prophylaxis costs pound 1500- pound 2213 per patient depending on published estimates of relative risk reduction. Mean estimated creatinine clearance at 1 year was 70.0 ml/min in patients who experienced no infection, 47.7 ml/min in patients who experienced infection but no disease, and 39.6 ml/min in patients who experienced CMV disease (P < 0.001). The incidence of acute rejection in these groups was 7.1, 14.3 and 35%, respectively (P = 0.13). CMV surveillance strategies may cost slightly less but may have a deleterious effect on long-term outcome compared with prophylaxis.

Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants

AbstractOral valacyclovir for cytomegalovirus (CMV) prophylaxis in bone marrow transplantation (BMT) was investigated in a randomized, double-blind, acyclovir-controlled, multicenter clinical trial in recipients of allogeneic BMT who were CMV seropositive (or donor positive) before transplantation and were aged 13 years or older. Patients were randomized before BMT. All initially received intravenous acyclovir (500 mg/m2) 3 times daily until day 28 after transplantation or after discharge, then oral valacyclovir (2 g) or acyclovir (800 mg) 4 times daily until week 18 after transplantation. Evidence of CMV infection, CMV disease, and death were documented for 22 weeks. Primary end points were time to CMV infection (detection of CMV in blood, broncho-alveolar lavage) or CMV disease and survival. Preemptive CMV therapy was permitted. Seven hundred twenty-seven patients were evaluable for efficacy. After the administration of intravenous acyclovir, valacyclovir was significantly more effective than oral acyclovir in reducing the incidence of CMV infection. CMV infection or disease developed in 102 (28%) valacyclovir patients, compared with 143 (40%) acyclovir patients (HR, 0.59; 95% CI, 0.46-0.76; P < .0001). Survival did not differ between treatments (76% and 75% in the valacyclovir and acyclovir groups, respectively). The safety of oral valacyclovir was similar to that of high-dose oral acyclovir. Valacyclovir was more effective than acyclovir in preventing CMV reactivation in BMT recipients and showed a similar safety profile. CMV disease incidence was low, and no differences were observed between oral valacyclovir and acyclovir. Survival was similar in each group. Valacyclovir prophylaxis provides a clinically valuable intervention but must be part of an overall strategy for CMV prevention in BMT.

Cytomegalovirus infection and graft rejection in renal transplantation.

Cytomegalovirus (CMV) infection and CMV disease have been associated with acute and chronic graft rejection. The introduction of the sensitive CMV antigenemia pp65 assay for detection of CMV infection allowed us to study the time course of CMV infection and acute rejection and the long-term outcome in renal transplant recipients with and without a CMV risk constellation. Prospective single center study including 48 renal transplant recipients at risk for CMV infection (donor and/or recipient CMV seropositive) and a control group of 36 CMV seronegative recipients of CMV seronegative kidney donors. Evidence of CMV infection was monitored by the CMV antigenemia pp65 assay every 1 to 2 weeks and compared with the occurrence of acute rejection in the posttransplant period and graft function at 5 years. CMV infection developed in 83% (40/48) of patients of the CMV risk group within 4 months posttransplant. A total of 18 of patients experienced an acute rejection episode (control group 16/36; P=0.65). In 12/18 CMV infection followed rejection and in three patients antigenemia preceded the diagnosis of rejection. In three patients CMV antigenemia remained negative. Five-year follow up: Patient survival (44/48 vs. 31/36; P=0.48), graft survival (38/48 vs. 27/36; P=0.79), number of patients with at least one acute rejection episode: CMV risk group: 42.1%, control group 51% (P=0.46), serum creatinine: CMV risk group:130 +/- 66 micromol/iter, control group: 126 +/- 37 micromol/ liter (P=0.56), proteinuria: CMV risk group: 0.02 +/- 0.02 g/mmol creatinine, control group: 0.02 +/- 0.02 g/mmol creatinine (P=1.0). CMV infection within 4 months posttransplant, as defined by a positive antigenemia assay was not found to be a risk factor for acute graft rejection or chronic graft dysfunction at 5 years.