High prevalence of hepatitis A and B nonimmunity in pediatric liver transplant recipients.

BACKGROUND: Pediatric liver transplant recipients are at increased risk of post-transplant infections. The purpose of this study was to quantify hepatitis A and B non-immunity based on antibody titers in liver transplant recipients. METHODS: We conducted a retrospective chart review of 107 pediatric liver transplant recipients at a single medical center from 2000 to 2017. We compared hepatitis immune patients to non-immune patients and studied response to vaccination in patients immunized post-transplantation. RESULTS: Eighty-one percent of patients had pre-transplant immunity to hepatitis A whereas 68% had pre-transplant immunity to hepatitis B. Post-transplant hepatitis B immunity decreased to 33% whereas post-transplant hepatitis A immunity remained high at 82%. Older age and time since transplantation were significantly associated with hepatitis B non-immunity. Most patients responded to doses post-transplantation with 78% seroconversion following hepatitis A re-immunization and 83% seroconversion following hepatitis B re-immunization. CONCLUSIONS: Pediatric liver transplant recipients are at risk of hepatitis A and B non-immunity, particularly with respect to hepatitis B. Boosters post-transplant may improve immunity to hepatitis viruses.

Differential cytokine and chemokine expression during rejection and infection following intestinal transplantation.

BACKGROUND/OBJECTIVES: Rejection and infectious enteritis in intestinal transplant (ITx) patients present with virtually identical symptoms. Currently, the gold standard for differentiating between these two conditions is endoscopy, which is invasive and costly. Our primary aim was to identify differences in peripheral blood cytokines during episodes of acute cellular rejection (ACR) and infectious enteritis in patients with intestinal transplants. METHODS: This was a prospective, cross-sectional study involving ITx patients transplanted between 2000 and 2016. We studied 63 blood samples collected from 29 ITx patients during periods of normal (n = 24) and abnormal (n = 17) allograft function. PBMCs from whole blood samples were cultured under unstimulated or stimulated conditions with phytohemagglutinin (PHA). The supernatant from these cultures were collected to measure cytokine and chemokine levels using a 38-plex luminex panel. RESULTS: Our study found that cytokines and chemokines are differentially expressed in normal, ACR, and infectious enteritis samples under unstimulated conditions based on heatmap analysis. Although each cohort displayed distinctive signatures, only MDC (p = 0.037) was found to be significantly different between ACR and infectious enteritis. Upon stimulation of PBMCs, patients with ACR demonstrated increased immune reactivity compared to infectious enteritis; though this did not reach statistical significance. CONCLUSIONS: To our knowledge, this is the first comprehensive study comparing cytokine expression during acute rejection and infectious enteritis in intestinal transplant recipients. Our results suggest that cytokines have the potential to be used as clinical markers for risk stratification and/or diagnosis of ACR and infectious enteritis.

The Medication Level Variability Index (MLVI) Predicts Poor Liver Transplant Outcomes: A Prospective Multi-Site Study.

Nonadherence to immunosuppressant medications is a leading cause of poor long-term outcomes in transplant recipients. The Medication Level Variability Index (MLVI) provides a vehicle for transplant outcome risk-stratification through continuous assessment of adherence. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi-site study evaluated whether MLVI predicts late acute rejection (LAR). Four hundred pediatric (1-17-year-old) liver transplant recipients were enrolled and followed for 2 years. The a-priori hypothesis was that a higher MLVI predicts LAR. Predefined secondary analyses evaluated other outcomes such as liver enzyme levels, and sensitivity analyses compared adolescents to pre-adolescents. In the primary analysis sample of 379 participants, a higher prerejection MLVI predicted LAR (mean prerejection MLVI with LAR: 2.4 [3.6 standard deviation] versus without LAR, 1.6 [1.1]; p = 0.026). Fifty-three percent of the adolescents with MLVI>2 in year 1 had LAR by the end of year 2, as compared with 6% of those with year 1 MLVI≤2. A higher MLVI was significantly associated with all secondary outcomes. MLVI, a marker of medication adherence that uses clinically derived information, predicts LAR in pediatric liver transplant recipients.

Successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and parenteral nutrition dependence: a case report.

Pregnancy after solid organ transplantation is becoming more common, with the largest recorded numbers in renal and liver transplant recipients. Intestinal transplantation is relatively new compared to other solid organs, and reports of successful pregnancy are far less frequent. All pregnancies reported to date in intestinal transplant recipients have been in women with stable graft function. The case reported here involves the first reported successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and dependence on both transplant immunosuppression and parenteral nutrition (PN) at the time of conception. Pregnancy was unplanned and unexpected in the setting of chronic illness and menstrual irregularities, discovered incidentally on abdominal ultrasound at approximately 18 weeks' gestation. Rapamune was held, tacrolimus continued, and PN adjusted to maintain consistent weight gain. A healthy female infant was delivered vaginally at term. Medical complications during pregnancy included anemia and need for tunneled catheter replacements. Ascites and edema were improved from baseline, with recurrence of large volume ascites shortly after delivery. Successful pregnancy is possible in the setting of transplant immunosuppression, chronic intestinal graft dysfunction, and long-term PN requirement, but close monitoring is required to ensure the health of mother and child.

Pediatric health-related quality of life after intestinal transplantation.

As outcomes after ITx improve, greater emphasis is needed on HRQOL. The primary aims of this study were to (i) assess the feasibility of measuring HRQOL in pediatric ITx recipients, (ii) measure HRQOL using validated instruments, and (iii) compare HRQOL in ITx recipients to healthy normal (NL) children. The CHQ and Pediatric Quality of Life (PedsQL4.0) instruments were administered to both patients and parents at outpatient visits. All 24 eligible patients were enrolled. The median age at study enrollment was 6.0 yr (range: 2-18 yr), and the median time from transplant to study enrollment was 2.8 yr (range: 0.5-11.8 yr). The majority of subjects were male (58%), Latino (58%), and liver-inclusive (92%) recipients. For CHQ and PedsQL4.0, parental responses were significantly lower in multiple categories including physical health and social functioning compared to healthy norms. Patient responses were not different from NL using CHQ but using PedsQL4.0 were significantly lower in the school functioning subcategory and psychosocial health summary score. HRQOL as reported by children and families after ITx is significantly lower in multiple categories compared to NL.

Rejection and steroid dependence: unique risk factors in the development of pediatric posttransplant de novo autoimmune hepatitis.

Posttransplant de novo autoimmune hepatitis (d-AIH) is increasingly described as a long-term complication after pediatric liver transplantation (LT). d-AIH is characterized by graft dysfunction, the development of autoimmune antibodies and histologic evidence of hepatitis in liver transplant recipients without previous history of autoimmune liver disease. This study is a matched case-control, univariate analysis aimed at identifying risk factors for the development of d-AIH and evaluating response to treatment. From 1984 to 2003, 619 children received 788 LTs at a single center. Forty-one patients developed d-AIH and were matched with controls for year of LT, age at time of LT and diagnosis. The following variables were insignificant in the development of d-AIH: age, gender, race, initial diagnosis, ischemia time, graft type, Epstein-Barr virus and cytomegalovirus status, HLA typing and primary immunosuppression. Compared to controls, d-AIH patients were less likely to be on monotherapy immunosuppression or weaned off prednisone at the time of diagnosis. The d-AIH group relative to the controls had statistically significant greater numbers of rejection episodes. d-AIH was treated with prednisone and/or MMF in 39 of 41 patients and lead to significant improvements in liver function tests. Thirty-nine patients are alive at a mean of 4.0 years follow-up after diagnosis. Three have required retransplantation.

Nutritional outcomes following pediatric intestinal transplantation.

BACKGROUND: This study sought to describe the long-term nutritional outcomes of children after intestinal transplant (SBT). METHODS: Between 1991 and March 2005, 30 children received 33 SBT at a single center. Eligibility criteria included patient and graft survival >6 months. Weight, height, albumin, prealbumin, zinc (Zn), and essential fatty acid (EFA) levels were reviewed retrospectively. RESULTS: The 19 patients who met inclusion criteria had a median age at SBT of 2.9 years. The majority of patients were male, Latino, transplanted for necrotizing enterocolitis and received combined liver-SBT. All patients were weaned off total parenteral nutrition to elemental formula at a mean of 39 days post-SBT. Seventeen of 19 patients were Zn deficient and four patients were EFA deficient post-SBT. CONCLUSIONS: Pre-SBT most subjects were significantly deficient in anthropometric and biochemical parameters. Post-SBT the mean Z score for weight and height improved significantly at year 1, then leveled off in year 2. Serum protein levels improved from pre-SBT, yet remained low-normal. Zn deficiency was seen frequently after SBT and is under investigation. Children who developed EFA deficiency were on the same formula, receiving inadequate EFA supplementation. Successful SBT was associated with growth and maintenance of serum nutritional parameters but not with significant catch-up growth.