ABSTRACT
BACKGROUND: There has been an estimated fivefold increase in the number of children receiving parenteral nutrition (PN) at home in the past 10 years with some children approaching the age when they should be referred to adult services whilst still on treatment. Models of care for moving young people onto adult providers of PN at home are not yet well developed, and transition is a potentially dangerous time for young people with complex health needs. METHODS: A questionnaire to ascertain current experience and practices of transition in the context of home PN services was dispatched to 170 consultant gastroenterologists who were members of the British Association of Parenteral and Enteral Nutrition (BAPEN) and also to all 40 members of the Nutrition and IF working group of the British Society of Paediatric Gastroenterology and Nutrition (BSPGHAN). Anonymised returns were received from 12 adult and 18 paediatric centres. RESULTS: We estimate about 50% paediatric IF centres, and the three largest adult IF centres responded to the survey. We identified 14 young adults already transitioned and 43 currently in transition. The practices and processes of transition reported were highly variable. Time taken to achieve transition ranged from under 6 months up to 2 years. The most frequent concerns to be identified were confusion around care routines and psychological problems at the time of transition (in one third of respondents). CONCLUSIONS: We conclude that a transition pathway and service standards for adolescents on home PN should be developed, consideration should be given to checklists for practical aspects (e.g. pumps), key worker and psychology input to enhance emotional resilience of the young people and carers.
Subject(s)
Continuity of Patient Care , Parenteral Nutrition, Home , Adolescent , Adult , Child , Child Nutritional Physiological Phenomena , Child, Preschool , Enteral Nutrition , Humans , Infant , Infant, Newborn , Surveys and Questionnaires , United Kingdom , Young AdultABSTRACT
INTRODUCTION: The terminal ileum (TI) is important for the active reabsorption of bile salts and is the site of allograft rejection; disruption of enterohepatic circulation (EHC) may give insights to inflammatory and other physiologic processes at the TI. SUBJECTS AND METHODS: Four children aged 5 to 12 years who had received small bowel transplantation (SBTx), 3 recovering from post-transplant lymphoproliferative disease (PTLD) and 1 with acute rejection, were studied. Two of the 4 had stoma reversal. Another child (15 years) with progressive familial intrahepatic cholestasis (PFIC) and pruritus, despite liver transplantation and biliary diversion, was studied. Selenium homocholic acid taurocholate scanning ((75)SeHCAT) capsule was given orally (n = 3) or via introducer during endoscopy (n = 2); a baseline whole-body gamma camera scan was done 4 hours later and on days 1 to 5. RESULTS: The normal 3-day bile salt retention is 30% to 70% of baseline and normal adult biological half-life, t½ is 62 ± 17 hours. The results in children with a stoma were very low (0.1% at 7.6 hours; 5% at 17 hours). The children with reversed stoma had retention and t½ closer to the reference range (18% at 29 hours; 22% at 33 hours). The child with PFIC + biliary diversion had an initial very high gamma emission from the stoma bag suggesting excellent reabsorption of bile salts from his TI, but retention was 0.6% and t½ 9.8 hours, demonstrating efficient biliary diversion. CONCLUSION: These results confirm children with stomas malabsorb bile acids, which can be ameliorated after stoma closure. SeHCAT demonstrated that the biliary diversion was working well and may be helpful in preoperative assessment of abnormal EHC. The role of SeHCAT in SBTx requires further evaluation.
Subject(s)
Bile Acids and Salts , Cholestasis, Intrahepatic/surgery , Ileum/transplantation , Selenium Radioisotopes , Taurocholic Acid/analogs & derivatives , Transplant Recipients , Adult , Humans , Ileum/diagnostic imaging , Ileum/physiopathology , Male , Pilot Projects , Radionuclide ImagingABSTRACT
BACKGROUND & AIMS: The demand for home parenteral nutrition (HPN) services for children has risen over the past 20 years. To plan a strategy for delivery of care at regional level, we carried out a national point prevalence survey of HPN during February 2010. METHODS: Paediatric gastroenterologists in 33 hospitals known to have provided HPN services were identified from their membership of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition and participation in the British Intestinal Failure Survey (BIFS). Anonymised data were collated by the BIFS administrator and results compared with a similar study performed by the British Paediatric Surveillance Unit in 1993. Trends in underlying diagnosis were explored using the BIFS database for 2006-2009. RESULTS: 139 children on HPN were reported; a fourfold increase since 1993; six of these were older than 16 years. The regional point prevalence of HPN varied from 1.76 to 41.4 per million, with a mean of 13.7 patients per million. Short bowel syndrome had increased from 27% to 63% of cases. CONCLUSIONS: The large overall increase in numbers of HPN patients suggests that a national strategy needs to be developed for the management of chronic IF.
Subject(s)
Home Care Services/trends , Parenteral Nutrition, Home/trends , Adolescent , Child , Child, Preschool , Female , Geography , Home Care Services/standards , Humans , Infant , Intestinal Diseases/therapy , Male , Patient Discharge , Quality of Health Care , United KingdomABSTRACT
OBJECTIVE: Selected infants with short bowel syndrome (SBS) and progressive intestinal failure associated liver disease (IFALD) may benefit from isolated liver transplantation (iLTx). The aim of the study is to identify risk factors for unfavourable outcome in iLTx. PATIENTS AND METHODS: A retrospective review of medical records from 1998 to 2005 was undertaken. Risk factors were assessed by comparing long-term survivors with those who died after iLTx. RESULTS: Fifteen iLTx were performed in 14 infants with IFALD. All were parenteral nutrition (PN) dependent, but had tolerated enterally 54% (38-100) of energy intake before iLTx. Median residual bowel was 60 cm (30-200). Eight out of 14 had intact ileocaecal valve (ICV). Median bilirubin was 298 micromol/L (87-715) and all had portal hypertension. Eight out of 9 survivors were weaned from PN after median 15 months. In 4 out of 9 children, nontransplant surgery after iLTx facilitated intestinal adaptation. Growth velocity had improved at 3 years after iLTx (P=0.001). Five children who died had poor enteral tolerance following iLTx (P<0.002), which correlated with pretransplant dysmotility seen in 4 out of 5 children shown by contrast studies (P=0.02)and increased frequency of line infections before (>6/year P<0.04) and after (P<0.001) iLTx. CONCLUSIONS: Isolated liver transplantation is a lifesaving option for selected children with SBS and IFALD. Revised criteria are proposed: progressive IFALD; 50 cm functional bowel in absence of ICV or 30 cm with ICV; 50% daily energy intake tolerated enterally for 4 weeks with satisfactory growth; and children with dysmotile bowel should be assessed for combined liver/bowel transplant unless the dysmotility is resolved and associated with minimal line infections.
Subject(s)
Intestinal Diseases/surgery , Liver Diseases/surgery , Liver Transplantation , Short Bowel Syndrome/surgery , Body Size , Enteral Nutrition , Female , Gastrointestinal Motility , Growth , Humans , Infant , Intestinal Diseases/etiology , Intestinal Diseases/mortality , Kaplan-Meier Estimate , Liver Diseases/etiology , Liver Diseases/mortality , Liver Transplantation/mortality , Male , Parenteral Nutrition/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors , Short Bowel Syndrome/complications , Short Bowel Syndrome/mortality , Treatment OutcomeABSTRACT
Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interstitial lung disease, which responded to discontinuation of sirolimus. Pediatricians should be aware about the pulmonary side effects of sirolimus.
Subject(s)
Immunosuppressive Agents/adverse effects , Lung Diseases, Interstitial/chemically induced , Sirolimus/adverse effects , Asthma/diagnosis , Child, Preschool , Cytomegalovirus Infections/surgery , Diagnosis, Differential , Female , Graft Rejection/prevention & control , Hirschsprung Disease/surgery , Humans , Immunosuppressive Agents/therapeutic use , Infant , Liver Transplantation , Lung Diseases, Interstitial/diagnosis , Male , Sirolimus/therapeutic useABSTRACT
INTRODUCTION: Following intestinal transplant (SBT), the early diagnosis and treatment of rejection is a major management aim. The diagnosis of rejection is based on histology of stomal biopsies. Oral gentamycin (2.5 mg/kg) was used for selective decontamination of the digestive system. Our hypothesis was that gentamycin might be absorbed in the presence of graft dysfunction. AIM: Our goal was to assess the correlation between serum gentamycin level and the health of the intestinal graft. SUBJECTS AND METHODS: Among 33 SBT performed from 1993 to 2005, serum gentamycin levels were performed once weekly or more often when there was a suspicion of rejection. All data were analyzed retrospectively. RESULTS: Adequate trough levels were achieved for only 23 patients, six of whom had histologically proven rejection and only one did not have a raised gentamycin content. Five patients with raised levels but no rejection included two with severe intestinal ischemia and three with bowel obstruction/ileus. Four of the five patients required laparotomies. CONCLUSION: We concluded that in our study raised serum gentamycin levels were a good predictor of rejection or significant injury to the graft.
Subject(s)
Biomarkers/blood , Gentamicins/blood , Graft Rejection/diagnosis , Intestine, Small/injuries , Intestine, Small/transplantation , Transplantation, Homologous/pathology , Child, Preschool , Female , Graft Rejection/blood , Humans , Intestinal Diseases/classification , Intestinal Diseases/surgery , Male , Reproducibility of Results , Retrospective StudiesABSTRACT
The highlights of The Ninth International Small Bowel Transplantation Symposium included the latest results from the Intestinal Transplant Registry (ITR), which demonstrated that the number of transplants performed annually continued to rise to 180 per year, most of which were performed in the United States, where the greatest number of home parenteral nutrition (PN) patients live (a prevalence of around 40 per million or 10,000 individuals). The three largest programs in the United States all use anti-CD25 monoclonal antibodies, but three different forms of lymphocyte depletion are employed in induction protocols: (1) humanized monoclonal anti-thymocyte globulin; (2) pretreatment of the recipient with Campath; (3) pretreatment of the small bowel allograft with anti-lymphocyte globulin. The main gain in these new approaches has been in the reduction in tacrolimus and steroid exposure. Indeed, the Pittsburgh team reduced tacrolimus to alternate-day dosing and stopped steroids altogether at 6 months in some patients, recording 100% survival in the past 2 years. The ITR demonstration of a difference in survival between adult patients who are hospitalized (40% to 60%) versus those who are still at home (80% to 100% survival) when called to transplant makes it almost unethical to delay evaluating patients for small bowel transplantation once they start experiencing complications on home PN. The input of gastroenterologists is also crucial in making recommendations about isolated liver transplantation for individuals with a potential to come off PN. Several important papers with useful prognostic clinical data with respect to selecting patients for isolated liver transplant were presented. It is evident from demographic surveys that only 2% to 5% adult patients and 5% to 15% children in large, well-resourced PN programs will be unlucky enough to develop life-threatening complications, but they must have rapid access to small bowel transplantation in this event. It is therefore important that the collaboration between gastroenterologists and the intestinal transplant teams continues. These excellent results for small bowel transplantation mean that the time is right for a large cost-effectiveness study comparing small bowel transplantation with PN.
Subject(s)
Intestine, Small/transplantation , Transplantation, Homologous/statistics & numerical data , Humans , Immunosuppression Therapy/methods , Parenteral Nutrition , Registries , United StatesABSTRACT
UNLABELLED: The 3-year survival after small bowel transplantation (SBTx) has improved to between 73% and 88%. Impaired venous access for parenteral nutrition can be an indication for SBTx in children with chronic intestinal failure. AIM: To report our experience in management of children with extreme end-stage venous access. SUBJECTS: The study consisted of 6 children (all boys), median age of assessment 27 months (range, 13-52 months), diagnosed with total intestinal aganglionosis (1), protracted diarrhea (1), and short bowel syndrome (4), of which gastroschisis (2) and malrotation with midgut volvulus (2) were the causes. All had a documented history of more than 10 central venous catheter insertions previously. All had venograms, and 1 child additionally had a magnetic resonance angiogram to evaluate venous access. Five of 6 presented with thrombosis of the superior vena cava (SVC) and/or inferior vena cava. METHODS: Venous access was reestablished as follows: transhepatic venous catheters (5), direct intra-atrial catheter via midline sternotomy (4), azygous venous catheters (2), dilatation of left subclavian vein after passage of a guide wire and then placing a catheter to reach the right atrium (1), radiological recanalization of the SVC and placement of a central venous catheter in situ (1), and direct puncture of SVC stump(1). Complications included serous pleural effusion after direct intra-atrial line insertion, which resolved after chest drain insertion (1), displacement of transhepatic catheter needing repositioning (2), and SVC stent narrowing requiring repeated balloon dilatation. OUTCOME: Four children with permanent intestinal failure on assessment were offered SBTx, 3 of which were transplanted and were established on full enteral nutrition; the family of 1 child declined the procedure. In the remaining 2 children in whom bowel adaptation was still a possibility, attempts were made to provide adequate central venous access as feeds and drug manipulations were undertaken. One of them received liver and SBTx nearly 3 years after presenting with end-stage central venous access, because attempts to achieve independence from parenteral nutrition had failed. The other child died immediately after a transhepatic venous catheter placement, possibly from a nutritional depletion syndrome as no physical cause of death was found. Direct intra-atrial catheters in transplanted children proved to be adequate for the management of uncomplicated transplantation, although the usual infusion protocol had to be modified considerably, and the lack of access would have been critical if massive blood transfusion had been required during the transplant procedure. CONCLUSION: It was possible to reestablish central venous access in all cases. However, this was time consuming and difficult to assemble a skilled team consisting of one of more: surgeon, cardiologist, interventional radiologist, and transplant anesthetist. Small bowel transplantation is easier and safer with adequate central venous access, and we advocate liaison with an SBTx center at an early stage.
Subject(s)
Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/instrumentation , Catheters, Indwelling , Intestine, Small/blood supply , Intestine, Small/transplantation , Catheterization, Central Venous/methods , Child, Preschool , Equipment Failure , Humans , Infant , Male , Parenteral Nutrition , Thrombosis/etiology , Treatment OutcomeABSTRACT
Successful long term parenteral nutrition has transformed the prognosis for children with irreversible intestinal failure in the last three decades, but has also highlighted the long term complications: intestinal failure associated liver disease; recurrent catheter sepsis; and impaired venous access. Recent advances in small bowel transplantation and non-transplant surgical techniques now offer hope of sustained survival in the future without parenteral nutrition.
Subject(s)
Intestinal Diseases/therapy , Child , Humans , Intestine, Small/transplantation , Liver Transplantation , Malabsorption Syndromes/therapy , Parenteral Nutrition/adverse effects , Short Bowel Syndrome/therapy , Treatment OutcomeABSTRACT
Combination of cyclosporine (CsA) and tacrolimus immunosuppression post-liver transplantation (LT) and the chemotherapeutic drugs used to treat hepatoblastoma (HB), are nephrotoxic. We aimed to determine the severity and duration of nephrotoxicity in children following LT for unresectable HB. We reviewed all children undergoing LT for unresectable HB at the Liver Unit, Birmingham Children's Hospital, UK, from 1991 to July 2000. Thirty-six children undergoing LT for biliary atresia, matched for age and sex, were selected as controls to compare pre- and post-LT renal function. Renal function was determined by estimation of glomerular filtration rate (eGFR) derived from plasma creatinine using Schwartz's formula. Twelve children with HB (mean age of diagnosis 33 months) who underwent LT (mean age 47 months) and 36 controls (mean age of LT 34 months) were studied. CsA was the main immunosuppressive drug used in each group. The median eGFR before, and at 3, 6, 12, 24 and 36 months after LT in HB group was significantly lower than controls (93 vs. 152, 66 vs. 79, 62 vs. 86, 66 vs. 87, 64 vs. 94, 53 vs. 90 mL/min/1.73 m2, respectively; 0.01 < p < 0.03). The reductions in the median eGFR of both the HB group and controls before and at 36 months after LT were 49 and 41%, respectively. At 36 months after LT, there was a trend for partial recovery of the eGFR in the controls but not in the HB group. Children who underwent LT for unresectable HB had renal dysfunction before transplantation that persisted for 36 months after LT.
Subject(s)
Hepatoblastoma/surgery , Kidney/physiopathology , Liver Neoplasms/surgery , Adolescent , Child , Child, Preschool , Cyclosporine/therapeutic use , Female , Glomerular Filtration Rate , Humans , Immunosuppressive Agents/therapeutic use , Infant , Liver Transplantation , Male , Postoperative PeriodABSTRACT
BACKGROUND/PURPOSE: Extensive intestinal aganglionosis is rare. The diagnosis and treatment are known to be difficult and it had been considered to be fatal. The aim of this study was to review our experience with children with extensive intestinal aganglionosis. METHODS: Retrospective analysis was conducted in patients referred to the intestinal transplantation unit since 1993. Presentation and outcome were analysed looking at 2 groups who had either undergone previous subtotal intestinal resection (group I) or no or limited resection (group II). RESULTS: Eight children were selected (3 patients in group I and 5 in group II). Group I was remarkable in that patients all were referred early in age with progressing liver failure. Parents of one patient refused to accept transplantation as treatment, and he died one month later. Two noncirrhotic patients were maintained in the parenteral nutrition programme and currently progress well with enteral feedings. The other 5 patients underwent transplant, and 4 of 5 are alive after transplantation with a mean follow-up of 22.2 months (range 0.4 to 63.6). CONCLUSIONS: Subtotal resection of intestine at the time of diagnosis must be avoided. Conservative management with parenteral nutrition may be associated with long-term good outcome. Small bowel transplant may open new perspective in the management of patients with end-stage liver disease.
Subject(s)
Hirschsprung Disease/diet therapy , Hirschsprung Disease/therapy , Intestine, Small/transplantation , Female , Hirschsprung Disease/surgery , Humans , Infant , Infant, Newborn , Liver Failure/etiology , Liver Failure/therapy , Liver Transplantation/methods , Male , Parenteral Nutrition, Total/methods , Retrospective StudiesSubject(s)
Intestine, Small/transplantation , Kidney Transplantation , Liver Transplantation , Lymphangiectasis, Intestinal/surgery , Nephrotic Syndrome/surgery , Child, Preschool , Fatal Outcome , Female , Humans , Lymphangiectasis, Intestinal/complications , Nephrotic Syndrome/etiology , Postoperative Complications , Sepsis/etiologyABSTRACT
The liver develops from progenitor cells into a well-differentiated organ in which bile secretion can be observed by 12 weeks' gestation. Full maturity takes up to two years after birth to be achieved, and involves the normal expression of signalling pathways such as that responsible for the JAG1 genes (aberrations occur in Alagille's syndrome), amino acid transport and insulin growth factors. At birth, hepatocytes are already specialized and have two surfaces: the sinusoidal side receives and absorbs a mixture of oxygenated blood and nutrients from the portal vein; the other surface delivers bile and other products of conjugation and metabolism (including drugs) to the canalicular network which joins up to the bile ductules. There is a rapid induction of functions such as transamination, glutamyl transferase, synthesis of coagulation factors, bile production and transport as soon as the umbilical supply is interrupted. Anatomical specialization can be observed across the hepatic acinus which has three distinct zones. Zone 1 borders the portal tracts (also known as periportal hepatocytes) and is noted for hepatocyte regeneration, bile duct proliferation and gluconeogenesis. Zone 3 borders the central vein and is associated with detoxification (e.g. paracetamol), aerobic metabolism, glycolysis and hydrolysis and zone 2 is an area of mixed function between the two zones. Preterm infants are at special risk of hepatic decompensation because their immaturity results in a delay in achieving normal detoxifying and synthetic function. Hypoxia and sepsis are also frequent and serious causes of liver dysfunction in neonates. Stem cell research has produced many answers to the questions about liver development and regeneration, and genetic studies including studies of susceptibility genes may yield further insights. The possibility that fatty liver (increasingly recognized as non-alcoholic steatohepatitis or NASH) may have roots in the neonatal period is a concept which may have important long-term implications.
Subject(s)
Infant, Newborn/physiology , Liver/physiology , Fatty Liver/genetics , Fatty Liver/physiopathology , Humans , Infant, Premature/physiology , Liver/embryology , Liver/growth & developmentABSTRACT
Orthotopic liver transplantation (OLT) is effective therapy for end-stage liver disease but immunosuppression with calcineurin inhibitors (CNI) leads to significant nephrotoxicity, resulting in either a reduction of dosage to below the therapeutic level or omission of the drug altogether. Basiliximab (Bx) is a human/mouse chimeric monoclonal antibody that inhibits binding of interleukin-2 (IL-2) to IL-2 receptors and thus prevents proliferation of T cells, which is the main step in the development of acute cellular rejection. The aim of this study was to identify the role of Bx in the prevention of acute cellular rejection and in the reduction of nephrotoxicity in children post-liver transplantation. We evaluated three children (19 months, 22 months, and 11 yr of age; one male, two female) who were treated with Bx post-OLT on compassionate grounds. The indications were: nephrotoxicity in two children, requiring re-transplantation for hepatic artery thrombosis and recurrent giant cell hepatitis, respectively; and nephrotoxicity secondary to chemotherapy for hepatoblastoma in the third child. All patients received 10 mg of Bx, at OLT and on Day 4. Tacrolimus (0.15 mg/kg/day) was started at 48 h (n = 2) and cyclosporin (5 mg/kg/day) at 2 weeks (n = 1). Trough levels of tacrolimus were maintained at 5-8 ng/mL and trough levels of cyclosporin at 100-150 mg/L for the first 3 months. All patients received methylprednisolone (2 mg/kg) with azathioprine (1.5 mg/kg) (n = 2) and/or mycophenolate mofetil (20 mg/kg) (n = 1). The glomerular filtration rate (cGFR) was calculated using the Schwartz formula before and 10 weeks after transplant. Bx was found to be easy to administer and no major side-effects were reported. One child had two episodes of mild acute rejection at 5 and 9 weeks post-OLT and one developed chronic rejection requiring re-transplantation at 9 weeks post-OLT. One child did not develop rejection. The mean pretransplant cGFR was 58.1 (54.6-64.1) mL/min/m2. Within 10 weeks of transplantation, the cGFR had improved by 69% to a mean of 116 (88-157.6) mL/min/m2. To conclude, Bx was well tolerated in all children and had a renal sparing effect. It was effective in preventing early acute rejection, but the combination of Bx and low-dose CNI drugs did not prevent late acute or chronic rejection. Further studies to evaluate the appropriate levels of CNI immunosuppression with Bx are required.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Calcineurin Inhibitors , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Liver Transplantation , Recombinant Fusion Proteins , Antibodies, Monoclonal/administration & dosage , Basiliximab , Child , Drug Therapy, Combination , Female , Graft Survival/drug effects , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Infant , Kidney Diseases/chemically induced , Male , Receptors, Interleukin-2/antagonists & inhibitors , Treatment OutcomeABSTRACT
BACKGROUND: Neonates and small infants represent less than 5% of paediatric candidates for liver replacement. Most cases present under urgent conditions and receive grafts from large donors. Surgical techniques must be adapted for adequate graft preparation, vascular reconstruction, and abdominal closure. METHODS: Technical aspects and outcome of 15 liver transplantations in infants weighing less than 5 kg performed at our unit were analysed retrospectively. RESULTS: Liver transplantation was performed under urgent or highly urgent condition in 13 cases. Reduced or split liver grafts were used in all cases (median donor to recipient weight ratio, 9), including a monosegmental graft in 2 cases. In 10 cases, vascular reconstruction was done using a vascular conduit (5, 4, and 1 for artery, portal, and hepatic veins, respectively) and a delayed closure of the abdomen was necessary in 7 children. Postoperative complications were as follows: thrombosis of hepatic artery (n = 1) or portal vein (n = 1), gastrointestinal haemorrhage (n = 2), intraperitoneal bleeding (n = 1), biliary stricture (n = 2), septicaemia (n = 1). Two infants died of brain damage with a functioning graft. One child underwent retransplant for chronic rejection. CONCLUSIONS: Overall, survival rate is 60% (median follow-up, 34 months), which compares favourably with older patient groups when case mix is comparable.
Subject(s)
Liver Transplantation/methods , Age Factors , Body Weight , Diagnosis-Related Groups , Graft Rejection , Humans , Infant , Infant, Newborn , Liver/surgery , Liver Diseases/surgery , Liver Failure/surgery , Liver Transplantation/mortality , Liver Transplantation/statistics & numerical data , Membrane Microdomains , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Early and accurate diagnosis of Crigler-Najjar syndrome, which causes prolonged unconjugated hyperbilirubinaemia in infancy, is important, as orthotopic liver transplantation is the definitive treatment. AIM: To determine whether bilirubin pigment analysis of bile in infants with prolonged unconjugated hyperbilirubinaemia provides useful diagnostic information in the first 3 months of life. METHODS: Retrospective review of patients with prolonged unconjugated hyperbilirubinaemia referred to the liver unit, Birmingham Children's Hospital, for the diagnosis of Crigler-Najjar syndrome. Bile bilirubin pigment composition was determined by high performance liquid chromatography. Initial diagnoses were made based on the result of bile bilirubin pigment composition. Final diagnoses were made after reviewing the clinical course, response to phenobarbitone, repeat bile bilirubin pigment composition analysis, and genetic studies. RESULTS: Between 1992 and 1999, nine infants aged less than 3 months of age with prolonged hyperbilirubinaemia underwent bile bilirubin pigment analyses. Based on these, two children were diagnosed with Crigler-Najjar syndrome (CNS) type 1, six with CNS type 2, and one with Gilbert's syndrome. Five children whose initial diagnosis was CNS type 2 had resolution of jaundice and normalisation of serum bilirubin after discontinuing phenobarbitone, and these cases were thought to be normal or to have Gilbert's syndrome. One of the initial cases of CNS type 1 responded to phenobarbitone with an 80% reduction in serum bilirubin consistent with CNS type 2. In all, the diagnoses of six cases needed to be reviewed. CONCLUSIONS: Early bile pigment analysis, performed during the first 3 months of life, often shows high levels of unconjugated bilirubin or bilirubin monoconjugates, leading to the incorrect diagnosis of both type 1 and type 2 Crigler-Najjar syndrome.