Liver Transplantation In Children Research Articles

Liver Transplantation in Children With Congenital Cardiac Defects: A Case Report and a Short Literature Review

Advances in surgical techniques and follow-up of patients with complex congenital heart disease who were corrected in childhood increasingly survive to adolescence or adulthood. Increasingly anesthesiologists encounter these cases for major noncardiac surgery, including orthotopic liver transplantation (OLT) wherein there is an augmented risk of significant perioperative hemodynamic instability. We performed a successful OLT in a 12-year-old boy with end-stage cryptogenetic liver fibrosis and hepatopulmonary syndrome who was born with a double outflow right ventricle, pulmonary atresia, and pulmonary artery hypoplasia corrected at the age of 1 month. By the time he was considered for OLT his altered pulmonary valve apparatus resulted in severe pulmonary regurgitation, dilated right atrium and ventricle, and elevated right heart pressures. After a temporarily successful angioplasty he was at first placed on the waiting list, then removed, and finally relisted following implantation of a prosthetic pulmonary valve that resulted in significant reduction of right heart pressures.

The use of transient elastography and non‐invasive serum markers of fibrosis in pediatric liver transplant recipients

The use of non-invasive markers to diagnose liver allograft fibrosis is not well established in children after LTx. TE, FT, and ELF score were performed in 117 liver-transplanted children (60M, 8.9 [0.5-18.5]yr) and 336 healthy controls. Liver biopsy was available in 36 children. Results of histology and non-invasive markers were compared using correlation coefficient or Mann-Whitney U-test as appropriate. TE correlated best with histological degree of fibrosis (r=0.85 vs. r=0.04 [FT] or r=-0.38 [ELF]). Liver stiffness values for transplanted children without fibrosis were significantly higher than those of healthy controls (7.55 [5.4-20.4]kPa vs. 4.5 [2.5-8.9]kPa). Presence of rejection was a potent confounder for the performance of TE. Both TE and FT reflected clinical changes (acute rejection, cholestasis, increasing fibrosis) in a total of 16 patients who underwent serial measurements. TE correlates better with histological degree of fibrosis in liver-transplanted children than FT or ELF, but an individual baseline value needs to be determined for each patient. Normal or cutoff values for pathological degrees of fibrosis cannot be transferred from non-transplanted children. Follow-up studies, preferably with protocol biopsies, might help to improve the diagnostic quality of TE.

Results of single‐center screening for chronic hepatitis E in children after liver transplantation and report on successful treatment with ribavirin

RNA screening for HEV in 22 liver-transplanted children with chronic graft hepatitis out of a cohort of 267 liver-transplanted children detected a single patient with chronic HEV infection. Although this patient remained viremic for 33months, anti-HEV-IgG was not detectable with MP assay but with Wantai assay. We present the first case of successful ribavirin therapy in an immunosuppressed child with chronic HEV infection. In conclusion, chronic HEV infection in immunosuppressed children may not be detectable employing serological assays. Therefore, the most reliably screening method is screening for HEV-RNA. Chronic HEV infection in children can successfully be treated with ribavirin.

Long-Term Growth and Anthropometry after Childhood Liver Transplantation

To describe longitudinal height, weight, and body mass index changes up to 15 years after childhood liver transplantation. Retrospective chart review of patients who underwent liver transplant from 1985-2004 was performed. Subjects were age <18 years at transplant, survived ≥5 years, with at least 2 recorded measurements, of which one was ≥5 years post-transplant. Measurements were recorded pre-transplant, 1, 5, 10, and 15 years later. Height and weight data were available in 98 and 104 patients, respectively; 47% were age <2 years at transplant; 58% were Australian, and the rest were from Japan. Height recovery continued for at least 10 years to reach the 26th percentile (Z-score -0.67) 15 years after transplant. Australians had better growth recovery and attained 47th percentile (Z-score -0.06) at 15 years. Weight recovery was most marked in the first year and continued for 15 years even in well-nourished children. Growth impaired and malnourished children at transplant exhibited the best growth, but remained significantly shorter and lighter even 15 years later. No effect of sex or age at transplant was noted on height or weight recovery. Post-transplant factors significantly impact growth recovery and likely caused the dichotomous growth recovery between Australian and Japanese children; 9% (9/98) of patients were overweight on body mass index calculations at 10-15 years but none were obese. After liver transplant, children can expect ongoing height and weight recovery for at least 10-15 years. Growth impairment at transplant and post-transplant care significantly impact long-term growth recovery.

Microsporidia and Coccidia as Causes of Persistence Diarrhea Among Liver Transplant Children

We determined species/genotype(s) of enteric microsporidia and coccidia causing diarrhea among 44 liver transplant children in Shiraz Nemazee hospital using acid-fast-trichrome staining and polymerase chain reaction-sequencing techniques. Enterocytozoon bieneusi (genotype D), Cryptosporidium (parvum and meleagridis) were detected in 6.81% and 11.36% of the children, respectively.

The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation Following Liver Transplantation in Children with Immunodeficiencies

s / Biol Blood Marrow Transplant 19 (2013) S279eS312 S296 all patients are alive. At 18 months after transplantation, one patient experienced progressive pancytopenia, requiring red blood cell transfusion, in spite of the full donor chiemrism both in the bone marrow and peripheral blood T cells. Chimerism analysis of the peripheral blood T cells was analyzed later than 6 months post-transplant, showing mixed chimerism in 3 patients with stable hematopoiesis. The recovery of menstruationwas observed in all 4 evaluable young female patients at 3, 7, 8, and 9 months after transplantation, respectively. Conclusion: These results suggest that this regimen could be a safe and effective conditioning regimen of allogeneic HSCT for SAA both from sibling and unrelated donor. However, long-term follow-up is needed to further evaluate the dynamics of T-cell chimerism and the incidence of late-onset graft failure.

KidsETransplant: a platform for liver-transplanted children.

Since 1989, all pediatric liver transplants in Switzerland are centralized at the University Hospitals of Geneva (HUG). Approximately 125 children have received transplants since then, and their survival rate is greater than 90% - one of the highest in Europe. Maximizing the chances of success requires that patients understand and comply with follow-up treatment. The KidsETransplant project aims at helping the child - and his family - to better understand his health situation, to have access to shared resources and to be able to better communicate with healthcare professionals and other patients.

Management of Living Donor Liver Transplantation in Children - Focusing on Post-Transplant Progressive Graft Fibrosis with or without Clinical Graft Dysfunction -

Management of Living Donor Liver Transplantation in Children - Focusing on Post-Transplant Progressive Graft Fibrosis with or without Clinical Graft Dysfunction -

Impact of Body Mass Index on the Outcome of Liver Transplantation in Children

Impact of Body Mass Index on the Outcome of Liver Transplantation in Children

Medical management of the 'failing' Kasai portoenterostomy

The only effective treatment for 'failing' Kasai portoenterostomy is liver transplantation (LT). However, to maximise a patient's chances to achieve the proclaimed >95% survival with sequential surgical management, medical follow-up and treatment must be planned carefully. This includes routine fat-soluble vitamin supplementation with choleretics, aggressive nutritional support, regular ultrasonography, optimal general paediatric care, and psychological support for the family once complications arise. Careful timing of LT is of critical importance, although recent trends include earlier consideration of LT in children with biliary atresia. This management can only be offered through centralised, specialised national services. Due to its ramifications in paediatric surgery, dietetics, metabolic, social, adolescent and transplantation medicine, paediatric hepatology is a fine example of patient care that is genuinely multidisciplinary.

Conjugated Hyperbilirubinemia in Children

A variety of anatomic, infectious, autoimmune, and metabolic diseases can lead to conjugated hyperbilirubinemia, both in the newborn period and later in childhood. The pediatric practitioner is most likely to encounter conjugated hyperbilirubinemia in the neonatal period.It is crucial to maintain a high degree of suspicion for cholestasis in the persistently jaundiced newborn. The goal is recognition of conjugated hyperbilirubinemia between 2 and 4 weeks after birth, allowing for the prompt identification and management of infants who have biliary atresia, which remains the most common cause of neonatal cholestasis.

Evaluation of Risk Factors for Bleeding After Liver Biopsy in Children

Acetylsalicylic acid is used in liver-transplanted children to prevent thrombosis of the hepatic artery. We evaluated whether acetylsalicylic acid and other risk factors were associated with bleeding after percutaneous liver biopsy. Medical charts, laboratory results, imaging studies, and anesthesia charts of 275 ultrasound-guided liver biopsy procedures in 190 children were reviewed. A total of 178 biopsies were performed on native livers and 97 on transplanted livers. Three major and 28 minor bleeding incidents were found. The mortality rate was 0%. Acetylsalicylic acid had been given the last 5 days before 55 of the biopsy procedures and no increased risk of bleeding was found (odds ratio 0.96 [0.37-2.26]; P = 1.00). Low-molecular-weight heparin and biopsies from focal lesions were risk factors for bleeding complications. Acute liver failure was associated with increased risk for major complications (odds ratio 26.1 [3.3-205]; P = 0.01) and was a risk factor for major bleeding. Postbiopsy ultrasound the day after the procedure (n = 266 [96% of 275 biopsies]) revealed minor bleeding after 7.1% of the biopsies and after 2.6% of the ultrasounds revealed unsuspected bleeding, but none of these required intervention. Ultrasound-guided liver biopsy in children is a procedure with a low rate of major complications and a high rate of minor bleeding not requiring intervention. Treatment with low-dose acetylsalicylic acid did not increase bleeding incidence or total complication rate. Low-molecular-weight heparin and biopsies from focal lesions were risk factors for bleeding complications. Routine ultrasound the day after the procedure did not change handling of the patients.

Centrilobular necrosis as a manifestation of venous outflow block in pediatric malnourished liver transplant recipients – case reports

CLN is a frequent histological finding in biopsies after pediatric: LT, and its pathogenesis has not yet been fully clarified and has different causes. Among the vascular causes, VOB is sometimes difficult to diagnose, especially when technical variants such as split-liver, reduced-liver, or living-related LT are utilized. Three liver-transplanted malnourished children (ages 12, 20, and 28 months) developed altered LFTs and post-operative ascites with right pleural effusion (two cases) and jaundice (one case). Doppler ultrasound examinations were normal and liver biopsies showed CLN interpreted as severe ACR. There were no responses to the medical treatment. Additional investigation with CT angiography suggested obstructed hepatic vein drainage, which was confirmed by interventional radiology and angioplasty of the anastomosis between the hepatic vein and the inferior vena cava, with clinical and histological resolution. It is concluded that in malnourished children undergoing LT with technical variations, in which the occurrence of severe ACR is usually less common because of the severity of the patient condition, the finding of CLN should raise the possibility of VOB, so that excessive immunosuppression and its consequences can be avoided.

The Long-Term Outcome of Hepatic Artery Thrombosis After Liver Transplantation in Children: Role of Urgent Revascularization

Hepatic artery thrombosis (HAT), one of the most severe complications of pediatric orthotopic liver transplantation (OLT), often compromises graft and/or child survival. Of 590 OLT performed in 516 children over a 20-year period, 45 were complicated by early HAT, during the first 2 weeks after transplantation. Systematic Doppler ultrasonographic detection of HAT allowed successful surgical revascularization in 19 instances, resulting in a 20-year graft survival rate of 77% versus 24% of cases when revascularization was not attempted or failed. A combination of surgical emergency revascularization, biliary interventional radiology, biliary surgery and/or retransplantation resulted in an 80% 20-year patient survival rate, identical to that of transplanted children who did not experience early HAT. The majority of long-term survivors with their initial graft had normal liver tests, no biliary dilation on ultrasonography and minimal or moderate fibrosis on liver histology. A failed attempt at revascularization did not significantly alter patient survival. Despite these encouraging results, for the children and their parents to overcome the entire process in terms of reoperations, repeated radiological interventions, number of hospitalizations and emotional stress, remains an ordeal of such magnitude that it justifies renewed efforts to progress in the prevention of this complication.

Endocrine and Bone Metabolic Complications in Chronic Liver Disease and After Liver Transplantation in Children

With improved survival of orthotopic liver transplantation (OLT) in children, prevention and treatment of pre- and posttransplant complications have become a major focus of care. End-stage liver failure can cause endocrine complications such as growth failure and hepatic osteodystrophy, and, like other chronic illnesses, also pubertal delay, relative adrenal insufficiency, and the sick euthyroid syndrome. Drug-induced diabetes mellitus post-OLT affects approximately 10% of children. Growth failure is found in 60% of children assessed for OLT. Despite optimisation of nutrition, rarely can further stunting of growth before OLT be prevented. Catch-up growth is usually observed after steroid weaning from 18 months post-OLT. Whether growth hormone treatment would benefit the 20% of children who fail to catch up in height requires testing in randomised controlled trials. Hepatic osteodystrophy in children comprises vitamin D deficiency rickets, low bone mass, and fractures caused by malnutrition and malabsorption. Vitamin D deficiency requires aggressive treatment with ergocalciferol (D2) or cholecalciferol (D3). The active vitamin D metabolites alphacalcidol or calcitriol increase gut calcium absorption but do not replace vitamin D stores. Prevalence of fractures is increased both before OLT (10%-28% of children) and after OLT (12%-38%). Most fractures are vertebral, are associated with low spine bone mineral density, and frequently occur asymptomatically, but they may also cause chronic pain. Fracture prediction in these children is limited. OLT in children is also associated with a greater risk of developing avascular bone necrosis (4%) and scoliosis (13%-38%). This article reviews the literature on endocrine and skeletal complications of liver disease and presents preventive screening recommendations and therapeutic strategies.

76 Factors Associated with Development of Food Allergy in Liver-Transplanted Children

BackgroundThe development of food allergy (FA) after transplantation has been described mainly about liver transplantation in children (Pediatr Allergy Immunol. 2009; 20: 741–747). It has been becoming important issue in this population. Although tacrolimus immunosuppressive therapy has been considered a significant risk factor (J Allergy Clin Immunol. 2011; 127: 1296–1298), other risk factors are not identified yet. This study was undertaken to evaluate the risk factors other than tacrolimus immunosuppressive therapy.MethodsThis study was a retrospective analysis of pediatric liver transplant recipients in our hospital. We reviewed the medical records of all patients who underwent liver transplantation during study period. Data collected including preceding-hepatic diseases, the number of previous surgeries, age at liver transplantation and etc.ResultsBetween November 2005 and May 2010, 106 children received liver transplantation. The most common indication for liver transplantation was biliary atresia (BA; 47 patiens, 44.3%). The other conditions were: congenital metabolic diseases in 27 patients, fulminant hepatic failure in 19, liver cirrhosis in 6, congenital absence of portal vein in 3, congenital hepatic fibrosis in 2 and hepatic tumor in 2 patients. After transplantation, all the patients received immunosuppressive therapy based on tacrolimus regimen. Fifteen patients (10 female and 5 male) developed new-onset FA (14.2%). The average age at transplantation was 10 months and FA has been developed within 2 years (median 11 months, IQR, 4.5–19.0). Eleven patients with BA (23.4%) and 4 patients with the other conditions (6.8%) developed new-onset FA (P = 0.023). Among the patients who developed FA, the number of previous surgeries was significantly higher in patients with BA (P = 0.008).ConclusionsNew-onset food allergy after liver transplantation is now becoming a significant problem. We observed a trend toward an excess of FA in patients with BA compared to patients with other indications for liver transplantation. Patients with BA received surgical operations in several times before liver transplantation. Frequent operations might add some stimulation to generate new-onset FA and should be considered as a susceptible subgroup that requires specific attention.

Liver Transplantation in Children with Cystic Fibrosis: Experience in our Centre and Preliminary Results with a Combined En Bloc Liver-Pancreas Graft

Cystic fibrosis (CF) is a multisystemic disease, with some patients developing end-stage liver disease (ESLD), requiring liver transplantation (LT). These children usually present with severe mutations of the CFTR gene. Almost 100% of patients with severe mutations develop exocrine pancreatic insufficiency, leading later to endocrine insufficiency. Immunosuppression accelerates the development of insulin-dependent diabetes (IDD) in transplanted children with CF. Our aims were: (1) to analyze our experience with CF-related ESLD children who received LT, and the relationship to the development of IDD; (2) to report our preliminary results with en bloc liver-pancreas transplantation (CLPT). 9 children (6M/3F) with CF and ESLD underwent LT between 1993 and 2010; median age and weight were 12.3 years (range: 5.4-17.0) and 36.7 kg (range: 14.2-58.5), respectively. 4 patients received a whole graft, 4 had reduced grafts (1 split) and 1 underwent CLPT. Immunosuppression followed the protocols at the time of transplantation. Liver function was restored in all patients and none of them needed re-transplantation. Median follow-up was 105 months (range: 4-206). 1 child died of respiratory failure at 23 months after transplantation while awaiting pulmonary transplantation. Survival (Kaplan-Meier) at 105 months was 87.5%. 4 children already had IDD before transplantation and 3 developed diabetes immediately after transplantation. 2 had not developed IDD at the end of the study: the youngest at the time of LT (5.4 years, follow-up 7.1 years) and the girl who had had CLPT and who recovered normal exocrine and endocrine pancreatic function after transplantation. LT is a realistic option to treat CF-related ESLD children. IDD is common in these patients. En bloc liver-pancreas transplantation is an appealing option, since it simultaneously restores exocrine function and prevents IDD. This procedure has clear technical advantages over simultaneous isolated liver and pancreas transplantation.

A Universal Preemptive Therapy for Cytomegalovirus Infections in Children After Live-Donor Liver Transplantation

Cytomegalovirus (CMV) infection remains the most common and critical viral infection that occurs after liver transplantation (LT). The current set of guidelines recommends prophylaxis over a preemptive therapy for pediatric LT; however, the data regarding the optimal approach after LT in children are limited. We conducted a universal preemptive therapy for CMV infection in 113 children (median: 16 months) after live-donor LT at the largest pediatric LT center in Japan between November 2005 and August 2009. CMV-pp65 antigenemia was monitored weekly regardless of the subjects' CMV serostatus after LT, and ganciclovir therapy was initiated when CMV-pp65 antigenemia was positive. The overall success rate of LT was 91.7%. CMV-pp65 antigenemia became positive in 37 (33%) recipients, and the positivity with their CMV serostatus was as follows: donor (D)+/recipient (R)-: 62%, D+/R+: 36%, D-/R+: 11%, and D-/R-: 8%. Among the D+/R- (n=29) and D+/R+ (n=44) recipients, 38% (n=11) and 64% (n=28) recipients were able to avoid the use of ganciclovir, respectively. Human CMV disease was documented in six (5%) recipients, and they were successfully treated with ganciclovir without any sequelae. A universal preemptive therapy for CMV infection after live-donor LT was successful for reducing the use of antiviral agents and for controlling CMV infection and disease in children.

Issues on Long-term Management after Liver Transplantation in Children

With advancements of liver transplantation, the patient’s survival improved remarkably. Thus the long-term survivors are increasing especially for the pediatric liver transplantation recipients. Consequently they are facing the challenge of maintaining graft function while minimizing long-term complications. In this review, I will discuss calcineurin inhibitor toxicity, problems with steroid, adherence to medical regimen, posttransplant growth, chronic graft dysfunction, tolerance.

11 REDUCED LEFT LATERAL SECTOR LIVER TRANSPLANTATION IN CHILDREN UNDER 10 KG-LESS IS BETTER

11 REDUCED LEFT LATERAL SECTOR LIVER TRANSPLANTATION IN CHILDREN UNDER 10 KG-LESS IS BETTER