Pediatric Small Bowel Transplantation Research Articles

Nutrition support considerations in pediatric small bowel transplantation.

Enteral autonomy is the primary goal of intestinal failure therapy. Intestinal transplantation (ITx) is an option when enteral autonomy cannot be achieved and management complications become life-threatening. The purpose of this review is to summarize existing medical literature related to nutrition requirements, nutrition status, and nutrition support after pediatric ITx. Achieving or maintaining adequate growth after intestinal transplant in children can be challenging because of episodes of rejection that require the use of corticosteroids, occurrences of infection that require a reduction or discontinuation of enteral or parenteral support, and fat malabsorption caused by impaired lymphatic circulation. Nutrient requirements should be assessed and modified regularly based on nutrition status, growth, ventilatory status, wound healing, and the presence of complications. Parenteral nutrition (PN) should be initiated as a continuous infusion early postoperatively. Enteral support should be initiated after evidence of graft bowel function and in the absence of clinical complications. Foods high in simple carbohydrates should be limited, as consumption may result in osmotic diarrhea. Short-term use of a fat-free diet followed by a low-fat diet may reduce the risk of the development of chylous ascites. Micronutrient deficiencies and food allergies are common occurrences after pediatric ITx. Enteral/oral vitamin and mineral supplementation may be required after PN is weaned. Nutrition management of children after ITx can be challenging for all members of the healthcare team. Anthropometric parameters and micronutrient status should be monitored regularly so that interventions to promote growth and prevent or reverse nutrient deficiencies can be implemented promptly.

PE-27: Long-term Nutritional Status in Pediatric Small Bowel Transplantation

PE-27: Long-term Nutritional Status in Pediatric Small Bowel Transplantation

Acute Inpatient Complications after Pediatric Small Bowel Transplantation: A 15-Year Review from the Nationwide Inpatient Sample Database

Journal of the American College of Surgeons 229(4):p S198, October 2019. | DOI: 10.1016/j.jamcollsurg.2019.08.435

Antibody-mediated rejection in pediatric small bowel transplantation: Capillaritis is a major determinant of C4d positivity in intestinal transplant biopsies.

The diagnostic criteria for antibody-mediated rejection (ABMR) after small bowel transplantation (SBT) are not clearly defined, although the presence of donor-specific antibodies (DSAs) has been reported to be deleterious for graft survival. We aimed to determine the incidence and prognostic value of DSAs and C4d in pediatric SBT and to identify the histopathologic features associated with C4d positivity. We studied all intestinal biopsies (IBx) obtained in the first year posttransplantation (N=345) in a prospective cohort of 23 children. DSAs and their capacity to fix C1q were identified by using Luminex technology. Eighteen patients (78%) had DSAs, and 9 had the capacity to fix C1q. Seventy-eight IBx (22.6%) were C4d positive. The independent determinants of C4d positivity were capillaritis grades 2 and 3 (odds ratio [OR] 4.02, P=.047 and OR 5.17, P=.003, respectively), mucosal erosion/ulceration (OR 2.8, P=.019), lamina propria inflammation grades 1 and 2/3 (OR 1.95, P=.043 and OR 3.1, P=.016, respectively), and chorion edema (OR 2.16, P=.028). Complement-fixing DSAs and repeated C4d-positive IBx were associated with poor outcome (P=.021 and P=.001, respectively). Our results support that capillaritis should be considered as a feature of ABMR in SBT and identify C1q-fixing DSAs and repeated C4d positivity as potential markers of poor outcome.

Successful Treatment Using Ebstein Barr Virus-Specific Cytotoxic T-Lymphocytes for Post-Transplant Lymphoproliferative Disorder in Pediatric Small Bowel Transplantation

Successful Treatment Using Ebstein Barr Virus-Specific Cytotoxic T-Lymphocytes for Post-Transplant Lymphoproliferative Disorder in Pediatric Small Bowel Transplantation

Immune Memory After Intestinal Transplantation – what can we learn from T cell immunophenotypes over time?

Introduction: Examination of peripheral blood mononuclear cells (PBMCs) via immunophenotyping has been shown to be a useful, non-invasive method of diagnosing acute cellular rejection (ACR) following intestinal transplantation (ITx).[1] Aims: To characterize (1) differences in the peripheral blood T cell immunophenotype during episodes of ACR and viral enteritis and (2) changes in naïve and central/effector memory T cells over time. Methods: An IRB-approved, longitudinal study of ITx recipients was performed. Blood was collected during serial routine visits at least 6 months apart and episodes of graft dysfunction (high fecal outputs, nausea/vomiting, and/or gastrointestinal bleeding). Samples from routine visits were classified as early post-ITx (<5 yrs) and late post-ITx (>5 yrs). PBMC immunophenotyping was performed with multi-color monoclonal antibody panels. Cell fluorescence was acquired on an LSR Fortessa. Analysis was performed with Flowjo V10. Statistical analyses included t-tests using Stata. Results: 11 pediatric ITx recipients who received 14 grafts were included. 57% were liver-intestinal grafts. 28 samples were analyzed (range of 1–5 samples per patient): 20 were collected on routine visits and 8 during episodes of graft dysfunction. There were no significant differences in markers of exhaustion (PD1+, KLRG1+, CD57+), Th17 effector cells, or T regulatory cells in normal (n=11) vs graft dysfunction (n=8). There were multiple statistically significant differences in T cell subsets in the early (n=7) vs late (n=13) groups (Table 1). Naïve T cells were higher in the early post-ITx group and T central memory cells were higher in the late post-ITx group. Conclusion: Over time, there is a shift in the T cell immunophenotype from naïve to central memory cells. Additional studies are needed with larger cohorts to identify T cell differences associated with episodes of graft dysfunction. Further elucidating T cell immunophenotypes over time will lead to a better understanding of immune memory and its clinical implications in ITx.FigureReference: 1. Ashokkumar C et al. Allospecific CD154+ T cells identify rejection-prone recipients after pediatric small-bowel transplantation. Surgery. 2009; 146:166–73.

Pediatric small bowel transplantation.

Intestine has become a transplantable organ due to the improvement in immunosuppressive drugs. The early referral to a reference unit is crucial in prognosis. There are still some pending issues like chronic rejection, the knowledge of the role of DSA development or early noninvasive detection of acute rejection. The appearance of tacrolimus and mTOR, and the use of induction therapy have marked a turning point with better graft and patient survival rates. The inclusion of the liver in the graft seems to have a protective effect. Surveillance of opportunistic infections has also contributed to improved results. Infection, post-transplant lymphoproliferative disease, rejection and GVHD have still a major role in survival; however, antibody-mediated rejection has gained increased attention. Parenteral nutrition remains the main therapeutic resource in the management of intestinal failure, but intestinal transplant is a therapeutic option when this therapy has failed. Finding the balanced immunosuppression that minimizes risk of rejection while preventing occurrence of complications like post-transplant lymphoproliferative disease or GVHD is an ongoing challenge. The current survival rates of intestinal transplantation are similar to other solid organ transplant.

Incidence of bloodstream infections in small bowel transplant recipients receiving selective decontamination of the digestive tract: A single-center experience.

Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, tobramycin, and amphotericin B. The incidence of CLABSI, infections outside the bloodstream, and rejection episodes were compared between study periods. The incidence of CLABSI did not differ between study periods (6.9 CLABSI vs. 4.6 CLABSI per 1000 catheter days; p = 0.727), but gram positives and Candida predominated in the first 30 days. Incidence of bacterial infections outside the bloodstream did not differ (p = 0.227). Rejection occurred more frequently during the first month following transplant (p = 0.302). SDD does not alter the incidence of CLABSI, bacterial infections outside the bloodstream, or allograft rejection in the immediate 30 days post-transplantation. However, SDD does influence CLABSI organism types (favoring gram positives and Candida) and Candidal infections outside the bloodstream.

Autoantibodies to red blood cell antigens occur frequently with hemolysis among pediatric small bowel transplant recipients: clinical implications and management.

Reports have linked pediatric solid organ transplant recipients with the development of hemolytic autoimmune antibodies, especially in the setting of the immunosuppressant tacrolimus. This study aims to identify whether these observations also occurred at an institution that frequently performs pediatric multivisceral transplants and to characterize the treatment and outcome. Chart review was performed on all patients with RBC autoantibodies. Laboratory and clinical data were used to identify hemolysis. For transplant recipients with RBC autoantibodies, the type of transplant and outcome of the AIHA were profiled. One hundred twenty-eight patients were identified with RBC autoantibodies, of which 22 patients were solid organ transplant recipients, including 18 SB graft recipients. Sixteen of the 18 had evidence of hemolysis. The incidence rate of AIHA in this population is estimated to be 10%, resulting in significant cost. Treatment included immunosuppressant modulation, steroids, IVIG, and plasma exchange, with 12 of the 16 patients responding. RBC autoantibodies occur in up to 10% in pediatric SB transplant recipients, with high cost of obtaining compatible blood. Neither tacrolimus nor receipts of a donor spleen were associated with the development of AIHA. Treatment using steroids and IVIG appears to be effective.

Imaging in pediatric small bowel transplantation.

Small bowel transplantation, alone or with other organs as multivisceral transplantation, is performed for patients with chronic intestinal failure. With advancing surgical techniques and improved post-surgical management, survival of these patients has increased tremendously in the last two decades. The radiologist has an important role in the preoperative and postoperative management of these patients. Knowledge of surgical techniques and post-surgical complications seen in the transplant recipient is necessary for adequate management of these patients.

Risk Factors for C. difficile Infections Following Pediatric Small Bowel Transplantation.

Risk Factors for C. difficile Infections Following Pediatric Small Bowel Transplantation.

Clinicopathologic features of post‐transplant lymphoproliferative disorders arising after pediatric small bowel transplant

Few studies examined the clinicopathologic features of PTLD arising in pediatric SBT patients. Particularly, the association between ATG and PTLD in this population has not been described. Retrospective review of 81 pediatric patient charts with SBT--isolated or in combination with other organs--showed a PTLD incidence of 11%, occurring more frequently in females (median age of four yr) and with clinically advanced disease. Monomorphic PTLD was the most common histological subtype. There was a significant difference in the use of ATG between patients who developed PTLD and those who did not (p < 0.01); a similar difference was seen with the use of sirolimus (p < 0.001). These results suggested a link between the combination of ATG and sirolimus and development of more clinically and histologically advanced PTLD; however, the risk of ATG by itself was not clear. EBV viral loads were higher in patients with PTLD, and median time between detection of EBV to PTLD diagnosis was three months. However, viral loads at the time of PTLD diagnosis were most often lower than at EBV detection, thereby raising questions on the correlation between decreasing viral genomes and risk of PTLD.

5 Years Experience at University of Nebraska Medical Center with Bloodstream Infections after Pediatric Small Bowel Transplantation

Background: Limited data regarding the epidemiology of bloodstream infections (BSI) in small bowel transplant (SBT) recipients has been published. Methods: We reviewed the medical records of 98 pediatric patients who underwent SBT from January 2003 to December 2007. Patients characteristics were analyzed with Wilcoxon rank-sum, chi-square or Fisher's exact tests. We compared survival distributions between groups with log rank test. Results: 95 patients underwent one transplant and three patients underwent two transplants. The median age of the group was 1.48 years (range 0.62-17.58 years), and 53% were male. Characteristics of the patients presented in Table 1.Table: [Patients’ characteristics]68 patients (69.4%) developed at least one episode of BSI, with a total of 146 BSIs during the first year after transplantation. The median time-to-infection after transplant was 52.5 days (range 1-273 days). Gram-positive bacteria (96 isolates) were more frequently isolated than Gram-negative bacteria (52 isolates), with Enterococcus spp. being the most commonly identified (48 isolates), followed by coagulate-negative Staphylococcus (40 isolates). Patients who underwent combined-SBT were significantly younger than patient who underwent isolated-SBT [median age 1.3 years (range 0.6-13.8 years) vs. 2.4 (0.7-17.6 years); p=0.009] with similar gender distribution (p=0.57). Patients who developed BSIs were younger than those without BSIs [median age 1.4 years (range 0.6-14.6) vs. 2.1 (0.9-17.6); p=0.02], without a gender difference (p=0.97). Central line was present in 86.3% of the BSI and total parenteral infusion (TPN) was being administered in 72.6% BSIs during the 7 days prior infection. The sources of the BSIs were: central line 49.3%, abdomen 32.9%, lung 4.8%, skin and soft tissues 4.1%, urinary tract 0.7%, and unknown 7.5%. Acute cellular rejection was diagnosed in 8 (8.1%) patients, all of them had BSIs. PTLD was diagnosed in 18 (18.4%) patients of which 14 developed BSI. Six grafts were lost in the first year after transplantation, 4 in patients with BSIs and 2 in patients without BSIs (p=0.99). One year survival rate for patients without BSIs was 86.7% (95%CI: 68.3-94.8%) versus 72.1% in patients with BSIs (95%CI: 59.8-81.2%). Conclusions: Almost 70% patients developed infections after SBT, early after transplantation mainly related to a central line or intra-abdominal process. Patients with BSIs were younger than those without, the majority had central line and were on TPN. Patients without BSIs tended to have a better survival rate.

5 Years Experience at University of Nebraska Medical Center with Bloodstream Infections after Pediatric Small Bowel Transplantation

Background: Limited data regarding the epidemiology of bloodstream infections (BSI) in small bowel transplant (SBT) recipients has been published. Methods: We reviewed the medical records of 98 pediatric patients who underwent SBT from January 2003 to December 2007. Patients characteristics were analyzed with Wilcoxon rank-sum, chi-square or Fisher's exact tests. We compared survival distributions between groups with log rank test. Results: 95 patients underwent one transplant and three patients underwent two transplants. The median age of the group was 1.48 years (range 0.62-17.58 years), and 53% were male. Characteristics of the patients presented in Table 1.Table: [Patients’ characteristics]68 patients (69.4%) developed at least one episode of BSI, with a total of 146 BSIs during the first year after transplantation. The median time-to-infection after transplant was 52.5 days (range 1-273 days). Gram-positive bacteria (96 isolates) were more frequently isolated than Gram-negative bacteria (52 isolates), with Enterococcus spp. being the most commonly identified (48 isolates), followed by coagulate-negative Staphylococcus (40 isolates). Patients who underwent combined-SBT were significantly younger than patient who underwent isolated-SBT [median age 1.3 years (range 0.6-13.8 years) vs. 2.4 (0.7-17.6 years); p=0.009] with similar gender distribution (p=0.57). Patients who developed BSIs were younger than those without BSIs [median age 1.4 years (range 0.6-14.6) vs. 2.1 (0.9-17.6); p=0.02], without a gender difference (p=0.97). Central line was present in 86.3% of the BSI and total parenteral infusion (TPN) was being administered in 72.6% BSIs during the 7 days prior infection. The sources of the BSIs were: central line 49.3%, abdomen 32.9%, lung 4.8%, skin and soft tissues 4.1%, urinary tract 0.7%, and unknown 7.5%. Acute cellular rejection was diagnosed in 8 (8.1%) patients, all of them had BSIs. PTLD was diagnosed in 18 (18.4%) patients of which 14 developed BSI. Six grafts were lost in the first year after transplantation, 4 in patients with BSIs and 2 in patients without BSIs (p=0.99). One year survival rate for patients without BSIs was 86.7% (95%CI: 68.3-94.8%) versus 72.1% in patients with BSIs (95%CI: 59.8-81.2%). Conclusions: Almost 70% patients developed infections after SBT, early after transplantation mainly related to a central line or intra-abdominal process. Patients with BSIs were younger than those without, the majority had central line and were on TPN. Patients without BSIs tended to have a better survival rate.

Bloodstream Infections During the First Year After Pediatric Small Bowel Transplantation

Little information regarding bloodstream infections (BSIs) in small bowel transplantation has been published. We reviewed the medical records of 98 pediatric patients who underwent small bowel transplantation. Patients' characteristics were analyzed with Wilcoxon rank-sum, χ or Fisher's exact tests. We estimated the overall survival by the Kaplan-Meier method and compared survival distributions between groups with the log-rank test. Sixty-eight patients developed ≥1episode of BSIs (total of 146 episodes), and 69.1% of the first infections were diagnosed in the 3 months post-transplantation. The most common sources of infection were as follows: central venous catheters (49.3%) and intra-abdominal infections (32.9%). Central venous catheters were present in 86.3%, and total parenteral nutrition within 7 days before infection was administered in 72.6% of episodes. Gram-positive bacteria (96 isolates) were more frequently isolated than Gram-negative bacteria (52 isolates), with Enterococcus spp. being the most commonly identified (48 isolates), followed by coagulase-negative Staphylococcus (40 isolates). Patients with infections were younger than those without (median 1.4 versus 2.1 years, P=0.02). Four grafts were lost after transplantation in patients with BSIs and 2 in patients without BSIs (P = 0.99). One-year survival rate for patients without BSIs was 86.7% (95% confidence interval: 68.3%-94.8%) versus 72.1% in patients with BSIs (95% confidence interval: 59.8%-81.2%). Overall time to death was shorter in patients with BSIs than in patients without BSIs (P=0.056). Almost 70% of small bowel transplantation recipients developed BSIs, mainly in the early months after transplantation. BSIs were mainly from a central venous catheter or intra-abdominal source. Enterococcus spp were the most frequently isolated organisms. Patients with BSIs had worse survival than patients with BSIs.

Risk Factors for Systemic Candida Infections in Pediatric Small Bowel Transplant Recipients

Fungal infections are an important cause of morbidity and mortality after small bowel transplantation (SBT). Little information about risk factors for Candida infections in pediatric SBT is available. We performed a 1:1 matched retrospective case-control study including 23 Candida culture-positive patients (cases) and 23 culture-negative patients (controls), matched based on age and time of transplantation. Patients' characteristics were compared using Wilcoxon rank-sum, χ, or Fisher exact tests. McNemar test was used to assess discordance between pretransplant and posttransplant fungemia. Univariate and multivariable conditional logistic regression analyses were performed to identify risk factors. The median age of the group was 1.87 years (range, 0.87-17.60); 59% patients were male. Within 1 month before transplant, 8.7% cases had fungemia and within 1-6 months before transplant, 30.4% cases had fungemia, compared with 69.6% within the 12 months after transplantation (P = 0.0001 and P = 0.02). By univariate analysis, total parenteral nutrition (TPN) (odds ratio [OR], 17.0 [95% confidence interval: 2.12, 2198]; P = 0.003) and antibiotic administration (OR, 18.99 [2.42, 2449]; P = 0.002) were risk factors for fungal infections. By multivariable analysis, both remained independent risk factors (TPN: OR, 10.86 [1.23, 1425], P = 0.03; antibiotic administration: OR, 12.83 [1.52, 1672], P = 0.01). Fungemia was significantly more frequent after SBT than before transplantation. Patients receiving TPN and antibiotic treatment had, respectively, 11 and 13 times higher risk of developing Candida infections after SBT.

Six‐month incidence of bloodstream infections in intestinal transplant patients

Intestinal transplantation has emerged as an established treatment for life-threatening intestinal failure. The most common complication and cause of death is infection. Risk of infection is highest during the first 6 months, as a consequence of maximal immunosuppression, greater than that required for any other organ allograft. We performed a retrospective chart review of all (56) adult and pediatric (<18 years) small bowel transplant patients at our institution between November 2003 and July 2007, and analyzed the 6-month post-transplant incidence of bloodstream infections (BSIs). We evaluated multiple risk factors, including inclusion of a colon or liver, total bilirubin >5, surgical complications, and acute rejection. A BSI developed in 34 of the 56 patients, with a total of 85 BSI episodes. Of these BSI episodes, 65.9% were due to gram-positive organisms, 34.1% gram-negative organisms, and 2.4% due to fungi. The most common isolates were Enterococcus species, Enterobacter species, Klebsiella species, and coagulase-negative staphylococci. Inclusion of the liver and/or a preoperative bilirubin >5 mg/dL appeared to increase the incidence of BSI (P = 0.0483 and 0.0005, respectively). Acute rejection and colonic inclusion did not appear to affect the incidence of BSI (P = 0.9419 and 0.8248, respectively). The BSI incidence was higher in children (P = 0.0058). BSIs are a common complication of intestinal transplantation. Risk factors include age <18, inclusion of the liver, and pre-transplant bilirubin >5. Acute rejection and colon inclusion do not appear to be associated with increased BSI risk.

Safety and Efficacy of CMX001 as Salvage Therapy for Severe Adenovirus Infections in Immunocompromised Patients

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.

Quantification of Intraepithelial Lymphocytes in Normal Pediatric Small Intestinal Allograft and Native Ilea

Background The small bowel acts as one of the first lines of defense against intraluminal infections and antigenic stimuli. Pediatric small bowel transplant patients are at particular risk from such agents, especially viral enteridities. Quantification of intraepithelial lymphocytes (IEL) in architecturally normal small intestinal mucosal biopsies plays an important role in the diagnosis of conditions such as celiac disease and some viral infections. No studies to date have been done to quantify IEL numbers in pediatric small bowel allografts and in native pediatric ilea. Our study investigated the IEL:enterocyte (EC) ratio in pediatric allograft and native ilea. Methods Hematoxylin and eosin slides from 50 surveillance endoscopic biopsies of small bowel allografts taken from patients <8 years of age and 50 terminal ileal biopsies from aged-matched control populations were reviewed. IEL:EC ratios were averaged from five well-oriented villi in each case. IEC numbers were compared between biopsies from proximal (afferent) and distal (efferent) limbs of double-barrel allograft stomas, as well as native terminal ilea. Results Within small bowel allografts, the average number of villus tip IELs was 1.3/20 ECs (standard deviation [SD] 0.6) in the proximal limb and 1.0/20 ECs in the distal (SD 0.6 P < .01). This value was significantly lower than in the control ilea (2.1/20 EC [SD 0.6]; P < .01, each). The overall distribution of lymphocytes was in a similar pattern throughout the villus with IEL:EC ratios on villus sides from proximal allografts, distal allografts, and native ilea being 1:20, 0.8:20, and 2:20, respectively. Conclusions The results suggest that approximately one to two IEL per 20 ECs at villus tips may represent a “normal” intraepithelial inflammatory cell population in small bowel allografts. The value is lower than that seen in age-matched native ileal biopsies. IEL numbers are significantly higher in the proximal limb compared to the distal limb of double-barrel stomas.

Adenovirus Infections in Pediatric Small Bowel Transplant Recipients

Adenovirus is commonly isolated from pediatric small bowel transplant recipients, but its clinical consequences remain poorly understood. The medical records of pediatric small bowel transplant recipients transplanted between January 2003 and December 2007 were reviewed. Thymoglobulin and basiliximab induction and tacrolimus-based immunosuppression were the standard of care. Logistic regression analysis was performed to determine risk factors for infection, descriptive analysis to determine adenovirus incidence, and Kaplan-Meier curve analysis to determine the timing of events after transplantation. Ninety-eight patients were included; 38 were positive for adenovirus (incidence 23.5%), 23 for viral shedding, 23 for infections. Nine infections developed in the first month after transplantation and 8 during the following 5 months. The small bowel was involved in 19 cases. Younger age at transplantation was a risk factor for adenovirus infection (odds ratio=0.81, 95% confidence interval, 0.663-0.994, P=0.04). Treatment of rejection did not increase the risk of adenovirus infection. Cytomegalovirus D+/R- sero-status was a protective factor (odds ratio=0.26, 95% confidence interval, 0.06-1.089, P=0.04). Adenovirus infections affected 24% of recipients and developed mostly during the first 6 months after transplantation. Small bowel is the most frequently involved site. Younger age at transplantation is a risk factor for adenovirus infection; whereas cytomegalovirus D+/R- sero-status seems to be protective.