Development of hepatopulmonary syndrome and portopulmonary hypertension in a paediatric liver transplant patient

BACKGROUND: Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are pulmonary vascular disorders which occur in patients with severe liver disease and/or portal hypertension. Although these syndromes are frequently diagnosed in patients undergoing assessment for liver transplantation, they seldom occur in the same patient. METHOD: This report describes a female paediatric patient, born with extra-hepatic biliary atresia, who required liver transplantation, at the age of 15, for secondary biliary cirrhosis. She had severe HPS prior to her first liver transplant, which resolved rapidly following surgery, as well as indirect evidence for PPH. She required a second liver transplant 1 yr later for chronic rejection. Whilst evaluating the patient for a third liver transplant, 4 yr later, severe PPH was discovered. The patient died 3 months later from right heart failure. CONCLUSION: HPS and PPH may coexist however they may show differing responses to liver transplantation with progression of PPH despite the resolution of HPS.     

Progressive cardiac failure following orthotopic liver transplantation for type IV glycogenosis

Orthotopic liver transplantation (OLT) has been proposed to treat patients with type IV glycogenosis because of early progressive cirrhosis. Reports have shown absence of disease progression in other organs after OLT and even regression of cardiac amylopectin infiltration in one case. We describe a 15-month-old child in whom a liver transplant was performed for type IV glycogenosis. There were no clinical signs of extrahepatic disease before OLT. Nine months later, the patient developed progressive cardiac insufficiency and died from cardiac failure. Because of massive amylopectin deposits, decreased myofibrils in cardiac cells, and exclusion of other causes of cardiac failure, death was attributed to amylopectinosis. Our observation contrasts with the Pittsburgh experience and suggests that cardiac amylopectionosis may progress after OLT.     

Indications and outcome of liver transplantation in tyrosinaemia type 1

A retrospective analysis was performed on 17 patients presenting with tyrosinaemia type 1 (TT1) between 1989-1997; 7 pre 1992 prior to the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) therapy and 10 post 1992. During this time, eight children (5 males) underwent orthotopic liver transplantation (OLT); six prior to the introduction of NTBC in 1992 and two on NTBC therapy. The primary indications for OLT pre-1992 were risk of hepatocellular carcinoma with evidence of hepatic dysplasia in all, associated with liver failure in two, and rise in !-fetoprotein (AFP) in four. Two of the ten treated with NTBC required OLT. The indications were non-response to NTBC in one child and development of hepatic dysplasia associated with poor quality of life in the second patient. Median age for OLT was 64 months (range 5-127 months) with a median weight of 24 kg (range 6-25 kg). The histology of hepatectomy specimens at transplantation showed: cirrhosis in 8, hepatic dysplasia in 6 and hepatocellular carcinoma in 1. Plasma tyrosine and AFP returned to normal in all cases. Urinary succinylacetone reduced but persisted in small amounts (median 7.7 7mol/mmol creatinine). Hypertrophic cardiomyopathy resolved in 3/3 patients. Hypoglycaemia, not responding to dietary therapy or NTBC treatment, resolved post-transplant in one patient. There were two deaths, one from primary non-function and one from chronic rejection. Late complications in survivors (n=6) include post-transplant lymphoproliferative disease of the iris in one child which resolved and renal dysfunction with a fall in glomerular filtration rate in three (50%). Median follow up post OLT is 6.7 years (range 1-7 years). Quality of life post-transplant in survivors is good with unrestricted diet in all. Conclusion Liver transplantation is an effective treatment for TT1 with good quality of life. The current indications of OLT in TT1 are non-response to NTBC, risk of malignancy and poor quality of life related to dietary restriction and frequency of blood sampling.     

HEMOPHAGOCYTIC SYNDROME: A Rare Life-Threatening Complication of Visceral Leishmaniasis in a Young Boy

The authors report a case of hemophagocytic syndrome (HPS) associated with acute visceral leishmaniasis (VL). A 4-year-old boy was admitted with high fever, hepatosplenomegaly, and pancytopenia. Elevated serum ferritin and triglyceride, low fibrinogen levels, and bone-marrow (BM) histiocytic hyperplasia with prominent hemophagocytosis were consistent with a HPS. An initial diagnosis of kala-azar was refuted because of negativity of BM aspiration and serology for this parasite, and the diagnosis of HPS was made. Three months after first admission, reevaluation of the BM aspiration revealed many amastigotes of Leishmania parasites. The serology of VL became positive, finally establishing the diagnosis of VL. Although specific therapy for VL was instituted, the patient died 4 weeks after the diagnosis.     

以急性肝功能衰竭为首发表现的噬血细胞综合征11例临床分析

目的：通过对11例以急性肝功能衰竭为首发症状的噬血细胞综合征(hemophagocytic syndrome,HPS)患儿的临床特征进行分析,提高对本病的早期识别。方法收集中国医科大学附属盛京医院2011年9月至2015年2月收治的以急性肝功能衰竭为首发表现的 HPS 患儿11例,对其临床表现、实验室检查结果、治疗方法、预后进行综合分析。结果 HPS 可以急性肝功能衰竭为首发症状,其特点为凝血功能严重异常,ALT、AST 升高,纤维蛋白原降低。11例患儿均有大于1周的热程和脾脏肿大;治疗上在应用肾上腺皮质激素及静注丙种球蛋白等抑制单核巨噬细胞系统的激活,早期依托泊苷进行化疗等基础上积极予以保肝降酶等综合治疗,部分病例伴有严重出血倾向,予血浆置换及连续血液透析滤过治疗。11例患儿中,存活1例,4例因多脏器功能衰竭死亡,自动出院6例随访均死亡。结论不明原因急性肝功能衰竭并伴有发热和血细胞减少的患儿应警惕 HPS,进行早期诊断和治疗以降低病死率。     

HEMOPHAGOCYTIC SYNDROME: A Rare Life-Threatening Complication of Visceral Leishmaniasis in a Young Boy

The authors report a case of hemophagocytic syndrome (HPS) associated with acute visceral leishmaniasis (VL). A 4-year-old boy was admitted with high fever, hepatosplenomegaly, and pancytopenia. Elevated serum ferritin and triglyceride, low fibrinogen levels, and bone-marrow (BM) histiocytic hyperplasia with prominent hemophagocytosis were consistent with a HPS. An initial diagnosis of kala-azar was refuted because of negativity of BM aspiration and serology for this parasite, and the diagnosis of HPS was made. Three months after first admission, reevaluation of the BM aspiration revealed many amastigotes of Leishmania parasites. The serology of VL became positive, finally establishing the diagnosis of VL. Although specific therapy for VL was instituted, the patient died 4 weeks after the diagnosis.     

Hemophagocytic syndrome and acute liver failure associated with ethylene glycol ingestion: a case report

The authors describe a case of accidental ethylene glycol poisoning in an 18-month-old boy who developed hemophagocytic syndrome (HPS). Ethylene glycol is a common substance in various antifreeze preparations. Acute ethylene glycol intoxication is a medical emergency that, if not diagnosed correctly and treated aggressively, will lead to serious neurological, cardiopulmonary, and renal dysfunction, and may result in death. The taking of a detailed history, physical examination, and laboratory testing are essential for diagnosis. To the best of the authors' knowledge this is the first case in the literature of a subject who developed HPS after ethylene glycol intoxication.     

Mycophenolate mofetil promotes prolonged improvement of renal dysfunction after pediatric liver transplantation: experience of a single center

Few studies have evaluated the long-term use of MMF in liver transplanted children with renal dysfunction. The aim of this study is to report the experience of a pediatric transplantation center on the efficacy and security of long-term use of a MMF immunosuppressant protocol with reduced doses of CNIs in stable liver transplanted children with renal dysfunction secondary to prolonged use of CsA or Tac. Between 1988 and 2003, 191 children underwent OLT and 11 patients developed renal dysfunction secondary to CNIs toxicity as evaluated by biochemical renal function parameters. The interval between liver transplantation and the introduction of the protocol varied from one to 12 yr. Renal function was evaluated by biochemical parameters in five phases: immediately prior to MMF administration; 3, 6, 12 and 24 months after the introduction of MMF. Among the patients, nine of them (82%) showed improvement of renal function parameters in comparison with the pretreatment values. The two patients that did not show any improvement were patients in whom the interval of time between OLT and the introduction of MMF was longer. All parameters of liver function remained unchanged. No episodes of acute or chronic rejection or increases in infection rates during the period were detected. Two patients developed transitory diarrhea and leukopenia that were reverted with reduction of MMF dosage. In conclusion, in liver transplanted pediatric patients with CNI-induced chronic renal dysfunction, the administration of MMF in addition to reduced doses of CNIs promotes long-term improvement in renal function parameters with no additional risks.     

Brain abscess in hepatopulmonary syndrome associated with biliary atresia

The first‐choice therapy for biliary atresia (BA) is Kasai hepatoportoenterostomy, which has been shown to greatly improve outcome. Various long‐term complications, however, such as portal hypertension and hepatopulmonary syndrome (HPS), can occur in patients with native liver. A rare case of brain abscess in an 11‐year‐old girl with HPS associated with BA is reported. The patient underwent hepatoportoenterostomy for BA at 53 days of age, with resolution of hyperbilirubinemia. At 10 years of age, she was diagnosed with severe HPS with right‐to‐left shunting, and preparations for liver transplantation proceeded. Three months after the diagnosis, she had a right parietal brain abscess. Given that the brain abscess enlarged in size, surgical drainage of the brain abscess was performed. The postoperative course was uneventful, but a slight left hemiplegia remained at discharge. The presumed mechanism of abscess formation in HPS may be right‐to‐left bacterial transit through intrapulmonary vascular dilatations and/or arteriovenous fistulae.     

Poor response to desmopressin acetate (DDAVP) in children with Hermansky-Pudlak syndrome

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a common genetic disorder in Puerto Rico. In children with HPS, bleeding is the most disturbing and incapacitating problem. Desmopressin (1-deamino-8-D-arginine vasopressin, (DDAVP)) has been recommended in the management of bleeding disorders characterized by platelet dysfunction, such as HPS. METHODS: Nineteen pediatric Puerto Rican patients with HPS and prolonged bleeding time (BT) were tested for response to administration of DDAVP. RESULTS: Baseline BT was abnormal in 18 (95%) of the patients. The BT following DDAVP administration improved in two cases (11%): one from 7.2 to 5.6 min and the other from 8 to 6 min (Tables II and III). BT measurements remained very prolonged (>15 min) in 17 (89%) of the patients. Patients with the HPS 1 gene mutation had a statistically significant correlation with the poor response following DDAVP (P = 0.03). CONCLUSIONS: DDAVP seldom improves the BT of Puerto Rican children with HPS. Response to DDAVP should be determined individually and platelet transfusion should remain the treatment of choice for a major bleeding episode or surgical procedure.     

Effects of an early referral system on liver transplantation for hepatoblastoma at Texas Children's Hospital

The purposes of this study were to analyze the effects of an ERS on time to transplantation and to describe our center's experience with OLT for HB. Patients who received OLT for HB between 2000 and 2013 were included. Patient and allograft characteristics, chemotherapy regimens, and prior surgical therapies were examined. The interval between diagnosis and OLT prior to and following the institution of an ERS for transplant was compared. Survival and tumor recurrence were analyzed. Nineteen patients received OLT for HB (mean age 33 months). All children received grafts from deceased donors. Two patients underwent prior resections. Tumor recurred in four patients (21.1%). Both patients who received salvage transplants experienced post‐OLT recurrence. Three of the four recurrences occurred in spite of adjuvant chemotherapy. There were three deaths: two from metastatic disease. One‐ and five‐yr survivals were 86.1% and 73.8%. After the institution of the ERS, the mean interval between tissue diagnosis and OLT was significantly reduced. Our series of 19 patients demonstrates a 21% recurrence of HB following OLT despite chemotherapy. Five‐yr survival reached 73.8%. A system of early referral can effectively reduce times between diagnosis and transplant.     

Immune response to rabies vaccination in pediatric transplant patients

Children have become engaged in a wider variety of activities as the success of solid organ transplantation has improved. These activities can result in exposure to infectious agents for which there are no data documenting the efficacy of standard treatment in children on immunosuppressive therapy. This is a retrospective review of five OLT patients and three RT patients who were potentially exposed to rabies during camp. They completed the immunoprophylaxis treatment for rabies exposure outlined by the CDC in the 2003 Red Book. Rabies titers were followed for six to 12 months post-immunization. All five OLT patients were on tacrolimus. All three RT patients were on tacrolimus, mycophenolate mofetil, and prednisone. At the time of exposure median age was 10.0 yr (8.4-17.3). None of the subjects developed rabies. A positive rabies titer, indicative of successful immunization, was present by one month in seven subjects and all subjects by six months. Rabies vaccination in pediatric transplant patients is safe and associated with the successful production of antirabies titers.     

Congenital hypothyroidism: causes for delayed initiation of treatment]

The aim of neonatal screening programs for congenital hypothyroidism is to ensure early treatment in order to prevent brain dysfunction. There are several reasons why infants are missed in the screening program. We report on three patients with congenital hypothyroidism, who had a pathological screening result and initiation of therapy was delayed. The first patient had an increased TSH level, but she was missed because of mistakes in the confirmatory serum test. During the follow-up the patient showed typical symptoms of hypothyroidism and got a thyroxine supplementation not before the age of three years. The second patient did not get a therapy before the age of six months because of the noncompliance of the parents and physicians. The third patient had a central hypothyroidism. The neonatal screening-program revealed no measurable TSH activity. Although the child had clinical signs of a severe hypothyroidism diagnosis was not made before the age of 5.5 months. Although different reasons are known for screening errors, all these 3 patients were missed because of failures in the follow-up of a pathological screening result, indicating a poor quality in the follow-up procedure.     

Secondary hemophagocytic syndrome after autologous hematopoietic cell transplant and immune therapy for neuroblastoma

Secondary hemophagocytic syndrome (HPS) has been described after autologous hematopoietic cell transplant (AutoHCT). We report two cases of secondary HPS after novel consolidation therapy for high‐risk neuroblastoma as part of an institutional phase 2 trial incorporating immunotherapy into a “standard” AutoHCT regimen. Both patients developed liver dysfunction beyond expected course of hepatic veno‐occlusive disease, coagulopathy, hyperferritinemia, and when evaluated, elevated soluble interleukin‐2 receptor and hemophagocytosis. These cases highlight the need for clinicians to have a high index of suspicion for immune‐related complications in patients receiving immune therapies.     

Successful liver transplantation in a child with Caroli's disease

Abstract:  CD is a rare autosomal recessive disease, characterized by multifocal cystic dilatation of intrahepatic bile ducts. The course of the disease is characterized by intrahepatic cholelithiasis, recurrent episodes of cholangitis, because of cholelithiasis, hepatic abscesses often ending in death caused by uncontrolled infection. Other conditions such as choledochal cyst and renal cystic disease are frequently associated, and patients have a higher risk for the development of cholangiocarcinoma. Endoscopic drainage of the bile duct is palliative and ineffective. OLT appears to be the treatment of choice. In monolobar cases partial liver resection has been shown to be a curative therapeutic option. We report on the course of disease in a Turkish girl who was diagnosed with CD in the neonatal period. At the age of 8.2 yr, she received OLT and is in good health 57 months post-transplantation.     

Food allergy after liver transplantation in children: a prospective study

Food allergy has been increasingly reported in children who had orthotopic liver transplantation (OLT). We aimed to conduct a prospective study to investigate the prevalence of sensitizations and food allergy in pediatric OLT recipients. We also aimed to identify potential risk factors. The study group consisted of 28 children (14 male, 14 female, mean age 4.96 ± 0.76 yrs) who had OLT. Total eosinophil count (TEC), total IgE, and specific IgEs were studied before and 3, 6, 12 months after OLT. Six patients (21%) developed multiple food allergies. Mean age of six patients at OLT who developed food allergy was younger compared to the non‐food allergy group (10.2 months vs. 68.9 months, p < 0.05). Food allergy has been developed within 1 yr in 5, and in 20 months in one patient after OLT. All six patients had cow’s milk and egg allergy after OLT. Five children developed wheat, one children developed lentil and another one developed peach allergy in addition to cow’s milk and egg allergy. Out of six food‐allergic patients after OLT, four children developed Epstein–Barr virus (EBV) infection prior to food allergy. Before OLT, TECs and total IgE levels were not differed among food allergic and non‐food allergic patients (p > 0.05). Mean of TECs were significantly higher in food allergic group compared to non‐food allergic group at each time point after OLT (p < 0.05). Though statistically insignificant, mean of total IgE levels were also higher in the food allergic group (p > 0.05). These findings suggest that food allergy should be considered after OLT in patients who are younger than 1 yr of age, who developed hypereosinophilia, high total IgE levels or EBV viremia.     

Successful venoarterial extracorporeal membrane oxygenation for prolonged hepatopulmonary syndrome following pediatric liver transplantation: A case report and review of the literature

HPS is a major complicating feature of end‐stage liver disease. Diagnosis is clinical, and LT is the only definitive treatment. While the general impression is that HPS improves quickly after transplantation, it may not always be the case. We describe the smallest reported child with HPS prior to LT and requiring prolonged venoarterial extracorporeal membrane oxygenation after LT; especially as it is a rare occurrence, physician managing such cases should be aware of the circumstances under which HPS may require specific treatment.     

Sequential transplantation and implications for clinical management: OLT followed by HCT and consequent RT in a pediatric patient

We report a case of a pediatric patient who required three separate transplants: OLT at the age 5, HCT at age 13 (8 years post‐OLT), and cadaveric RT at age 15 (10 years post‐OLT). The child initially presented with fulminant liver failure without known cause, ultimately undergoing OLT from his mother. He then developed SAA, for which he required HCT. Unfortunately, he developed ESRD secondary to prolonged CNI exposure, for which he underwent cadaveric RT. These processes then resulted in 7 years largely free from complications, during which a multi‐disciplinary team monitored the patient for complications. Regrettably, at the age of 21 he developed poorly differentiated mucinous adenocarcinoma of the colon which ultimately led to his demise. While there are case reports of patients requiring two sequential transplants, there is a paucity of reports of successfully completing three separate organ transplants in the same patient. Our case demonstrates progression of a pediatric patient through OLT, HCT, and RT with discussion of notable clinical implications. Secondarily, this case highlights the importance of coordination of care amongst various subspecialties to facilitate tandem transplantations and manage the complications of these processes. As pediatric patients have improved survival rates and may require multiple transplants, it remains important to highlight the feasibility as well as the complications of the tandem transplant process.     

Fading renal hyperfiltration in children following liver transplantation

In a prospective longitudinal study, we investigated the renal function (RF) of 23 children before and after orthotopic liver transplantation (OLT). The aim was to assess both the outcome of pretransplant hyperfiltration and the clinical nephrotoxic effects of cyclosporin A (CsA); children with decreased RF prior to OLT were therefore excluded. The RF study of the 13 remaining patients included glomerular filtration rate (GFR) and effective renal plasma flow (RPF) measured by inulin (Cin: mL/min/1.73 m2) and para-amino hippurate (Cpah: mL/min/1.73 m2) clearances, respectively. Hyperfiltration prior to OLT was observed in six children, i.e. Cin>170 [range 172-230] and Cpah>800 [808-1,133]. A significant decrease in RF was noted as soon as 6 months after OLT: Cin (mean+/-SD)=107+/-23 vs. 158+/-46 (p<0.003); Cpah=583+/-119 vs. 791+/-243 (p<0.004). This was due to loss of hyperfiltration in the six children, as there was no significant difference in RF before and 6 months after OLT in the other seven children. With a 36-month follow-up, there was no correlation between CsA trough blood level and RF. In conclusion, following OLT, RF underwent early changes owing to loss of prior hyperfiltration in children without impaired RF before OLT. In addition, no evidence of CsA nephrotoxicity was found and RF remained stable during follow-up.     

Liver transplantation in cystic fibrosis: A report from Baylor College of Medicine and the Texas Children's Hospital

CF affects one of 2000 Caucasians, and approximately 25% are found to have CFLD for which OLT may be indicated. Timing of transplantation, contraindications, and survival are still widely debated. We report the outcomes of OLT for pediatric patients with CFLD from the largest children's hospital in the United States. Our records since September 1998 were analyzed for all patients undergoing OLT for CFLD. Nine patients were then compared to similar patients in the UNOS/OPTN database (n = 155). Survivals were calculated with the Kaplan–Meier method and compared using the log‐rank test. All statistics were performed in SPSS 15.0. We performed OLT on nine pediatric patients with CFLD, with age ranging from nine to 17 yr at the time of transplant. Mean survival was 69.2 months; patient and allograft survivals at one and five yr were 88.9%, with one death at day 21 due to Aspergillus fumigatus sepsis. Two patients underwent concurrent multi‐organ transplantation. One patient required double lung transplantation four yr after isolated OLT. Comparison to the UNOS/OPTN database revealed a trend toward improved survival. Patients with CF can achieve favorable outcomes after OLT, as we report excellent survivals for pediatric patients with CFLD.