Andrea Briem-Richter

Effectiveness of Rex shunt in children with portal hypertension following liver transplantation or with primary portal hypertension

Abstract:  Portal vein thrombosis can occur as a result of primary anomalies, after liver transplantation, and for other reasons. It may result in severe complications secondary to portal hypertension, such as bleeding from esophageal or gastric varices, hypersplenism, or impaired somatic growth. In this retrospective study, we analyzed the outcome of 25 children who underwent a Rex shunt procedure. The following venous grafts were used as the shunt: the autologous internal or external jugular vein (n = 17) or a cryopreserved graft (n = 5); in three patients the umbilical vein was recanalized. The median follow up time was 109 months (range 18 days–146 months). The best results were achieved in patients in whom an autologous jugular vein segment was used as a vascular graft for the Rex shunt (shunt patency of 88%). In patients with a functioning shunt no further lower or upper gastrointestinal bleeding occurred. And in the entire study population hypersplenism syndrome improved after surgery. In our large cohort of pediatric patients, the Rex shunt has shown to be an effective method to eliminate portal hypertension and to revascularize the liver and thereby prevents the possible consequences of long‐term portosystemic shunting.

The use of everolimus in pediatric liver transplant recipients: first experience in a single center.

Nielsen D, Briem‐Richter A, Sornsakrin M, Fischer L, Nashan B, Ganschow R. The use of everolimus in pediatric liver transplant recipients: First experience in a single center. 
Pediatr Transplantation 2011: 15: 510–514.

Long-term Clinical Relevance of De Novo Donor-Specific Antibodies After Pediatric Liver Transplantation.

Background Anti-HLA antibodies and especially donor-specific antibodies (DSA) play a significant role in graft survival after solid organ transplantation. Their impact on long-term survival in adult liver transplantation (LT) is controversial, but they may be a risk factor. The effects of DSA after pediatric LT are still unclear. Methods We performed a retrospective evaluation of DSA in sera from 43 children who had received transplants at our tertiary center. Twenty-four patients had good long-term clinical and laboratory graft function (group 1), whereas 19 LT recipients suffered from histologically confirmed and clinically relevant chronic allograft rejection (group 2); 16 of these have already undergone retransplantation due to graft dysfunction. Inclusion criteria were availability of sera before the first LT to identify preformed antibodies in case of DSA positivity after LT and long-term follow-up at our institution. Sera were analyzed for anti-HLA antibodies using Luminex single antigen beads, where a mean fluorescence intensity value of more than 1500 was considered positive. Results The prevalence of DSA was 33% for group 1 and 68% for group 2. Antibodies were predominantly HLA class II. Values of mean fluorescence intensity were comparable in both groups. Only one of the DSA+ ve patients from group 1 exhibited preformed antibodies. In conclusion, pediatric patients with chronic rejection revealed a higher rate of de novo DSA, especially of HLA-class II DSA. Further studies are necessary to confirm these data with a larger pediatric cohort.

Immediate postoperative intensive care treatment of pediatric combined liver-kidney transplantation: outcome and prognostic factors.

Background. Studies reporting the immediate pediatric intensive care unit (PICU) treatment after combined liver-kidney transplantation (CLKT) are scarce, although this period is pivotal for survival and long-term outcome. Methods. We retrospectively analyzed all pediatric CLKT performed in our center between 1998 and 2010. Results. Sixteen patients underwent 17 CLKT at a median age of 5.3 years (range, 1.3–15.9 years). Median body weight at CLKT was 17.7 kg (range, 9.2–55 kg). Underlying diagnosis was primary hyperoxaluria type 1 in nine patients and autosomal recessive polycystic kidney disease in seven patients. Median time on PICU was 8.5 days (range, 3–68 days); however, patients with primary hyperoxaluria type 1 had a significantly longer stay (P=0.031). Median duration of ventilation was 1 day; however, five patients required ventilation for 25 to 52 days. Continuous veno-venous hemofiltration was applied in nine patients due to delayed kidney graft function, volume overload, or high plasma oxalate. Overall, the survival rate after CLKT was 100% and long-term outcome was very good at a mean follow-up of 3.6 years (range, 0.5–12.2 years). Waiting time, donor age, and donor-to-recipient weight ratio were found to be significant risk factors for an extended PICU stay (P=0.02, 0.0031, and 0.014, respectively). Conclusions. Immediate postoperative course after CLKT may be challenging and complex. However, excellent results can be achieved, even in small children.

The value of immunoprophylaxis for cytomegalovirus infection with intravenous immunoglobulin in pediatric liver transplant recipients receiving a low-dose immunosupressive regimen

Krampe K, Briem‐Richter A, Fischer L, Nashan B, Ganschow R. The value of immunoprophylaxis for cytomegalovirus infection with intravenous immunoglobulin in pediatric liver transplant recipients receiving a low‐dose immunosupressive regimen.
Pediatr Transplantation 2010: 14: 67–71.

Prevalence of polyomavirus viruria (JC virus/BK virus) in children following liver transplantation

Brinkert F, Briem‐Richter A, Ilchmann C, Kemper MJ, Ganschow R. Prevalence of polyomavirus viruria (JC virus/BK virus) in children following liver transplantation.
Pediatr Transplantation 2010: 14: 105–108.

Long‐term outcomes after liver transplantation for deoxyguanosine kinase deficiency: A single‐center experience and a review of the literature

Deoxyguanosine kinase (DGUOK) deficiency is a well‐known cause of hepatocerebral mitochondrial DNA depletion syndromes, which include a broad spectrum of clinical presentations. Affected patients often develop life‐threatening liver failure, but the benefits of liver transplantation (LT) are controversial because of the frequently severe neurological involvement due to the underlying mitochondrial disease. We describe the long‐term clinical course of 2 patients from our institution and provide an update on their outcomes after LT with this condition. Another 12 pediatric patients were identified through a systematic search of the literature. All 14 reported patients underwent transplantation in infancy despite mild to moderate neurological impairment in some cases. The 2 DGUOK‐deficient patients from our center displayed liver failure and mild to moderate neurological involvement. At the time of this writing, they had been followed for 5 and 8 years after LT, both patients were alive, and they had only mild neurological symptoms. Three of the 12 patients identified through the literature review survived for a long time (17, 12, and 23 years); 8 died during early follow‐up; and for 1 patient, no follow‐up information was available. The 1‐year survival rate was 64%; 36% survived for more than 5 years. The long‐term survivors had good quality of life. In conclusion, although survival after LT for DGUOK deficiency is lower than survival after LT for other indications, a significant proportion of patients benefit from LT with long‐term survival and a stable neurological situation despite initial neurological abnormalities. Nevertheless, a decision to carry out LT for patients with DGUOK deficiency remains difficult because neurological symptoms may occur and worsen after LT despite their absence before transplantation. Liver Transpl 20:464–472, 2014.

High prevalence of renal dysfunction in children after liver transplantation: non-invasive diagnosis using a cystatin C-based equation

BACKGROUND Chronic kidney disease (CKD) has been increasingly shown to be a negative prognostic factor after liver transplantation (Ltx). Creatinine-based glomerular filtration rate (GFR) formulas are notoriously insensitive. In children, non-invasive determination of GFR by measurement of serum cystatin C is feasible and repeatedly correlated to the gold standards of GFR measurements. The aim of our study was to determine GFR using cystatin C (GFR(cys)) in comparison with conventional calculated creatinine clearance (GFR(crea)) in the long-term follow-up after paediatric liver transplantation (pLtx) in a large number of patients. METHODS GFR of 168 children following liver transplantation was determined using cystatin C (GFR(cys)) and the Schwartz formula (GFR(crea)). In order to evaluate risk factors for CKD, a logistic regression analysis was performed. A multivariate model was applied to assess the impact of immunosuppressive treatment. RESULTS The mean follow-up after transplantation was 7.8 (0.44-15.72) years. Due to a high overestimation of GFR as demonstrated in a Bland-Altman plot, only three patients with CKD stages 2-3 were detected with GFR(crea) compared with 34 with GFR(cys) (P < 0.001). Thus, prevalence of CKD with GFR((cys)) < 90 mL/min/1.73 m2; was 30.4%, 7.6% and 27% in patients with 5, 10 and > 10 years of follow-up, respectively. Patients on cyclosporine had a significantly lower GFR than patients on tacrolimus. Logistic regression analysis did not show any significant risk factor for the development of CKD. CONCLUSIONS The cystatin C equation is a non-invasive and sensitive diagnostic tool to detect renal dysfunction in children after Ltx at an early stage. The choice of first-line calcineurin inhibitor has an important impact on the development of CKD.

Liver transplantation for fulminant hepatic failure in infancy: A single center experience

Abstract:  FHF is characterized by a high percentage of unknown causes leading to acute liver failure and furthermore by an increased morbidity and mortality prior to and post‐Ltx. In different transplant centers, the reasons leading to FHF differ significantly as well as outcome. We report our single center experience with 30 pediatric patients receiving a liver transplant for FHF, out of a total of 83 children presenting with FHF. The time to transfer patients to the transplant center after the diagnosis of FHF was long, with a median of 14 days (Ltx group) and 12 days (controls), respectively. In nearly half of the patients (n = 14) in the Ltx group, we were not able to establish an exact diagnosis prior to Ltx: 50% suffered from encephalopathy, and 13 patients were treated in the intensive care unit prior to transplant. Because of the availability of different surgical techniques, all children received a timely transplant [split (n = 18), living donor (n = 9), whole organ (n = 2), and reduced liver (n = 1)]. Patient survival was 93.4%, and graft survival was 83.4% for at least one yr follow‐up. Severe complications following Ltx included three cases with aplastic anemia and one child suffering from systemic mitochondrial depletion syndrome. The survival of patients treated medically was 83%. We conclude that a strong focus should be made on early referral to a specialized center and on improvement of diagnostic tools to timely detect the underlying reason for FHF. Results following Ltx for FHF are good.

Developments in pediatric liver transplantation since implementation of the new allocation rules in Eurotransplant.

Liver allocation in the Eurotransplant (ET) region has changed from a waiting time to an urgency‐based system using the model of end‐stage liver disease (MELD) score in 2006. To allow timely transplantation, pediatric recipients are allocated by an assigned pediatric MELD independent of severity of illness. Consequences for children listed at our center were evaluated by retrospective analysis of all primary pediatric liver transplantation (LTX) from deceased donors between 2002 and 2010 (110 LTX before/50 LTX after new allocation). Of 50 children transplanted in the MELD era, 17 (34%) underwent LTX with a high‐urgent status that was real in five patients (median lab MELD 22, waiting time five d) and assigned in 12 patients (lab MELD 7, waiting time 35 d). Thirty‐three children received a liver by their assigned pediatric MELD (lab MELD 15, waiting time 255 d). Waiting time in the two periods was similar, whereas the wait‐list mortality decreased (from about four children/yr to about one child/yr). One‐ and three‐yr patient survival showed no significant difference (94.5/97.7%; p = 0.385) as did one‐ and three‐yr graft survival (80.7/75.2%; and 86.5/82%; p = 0.436 before/after). Introduction of a MELD‐based allocation system in ET with assignment of a granted score for pediatric recipients has led to a clear priorization of children resulting in a low wait‐list mortality and good clinical outcome.