S. V. Beath

Nutritional care and candidates for small bowel transplantation.

Twenty two children were evaluated for small bowel transplantation between 1989 and 1994. Eight were unfit for transplantation and died within three months; a raised plasma bilirubin concentration (> 200 mumol/l) predicted death from liver failure within six months (p = 0.0001). The 11 children who were not managed by a multidisciplinary nutritional care team were less well nourished at referral, had more complications with intravenous feeding catheters, and greater early mortality while awaiting transplantation (p < 0.05). It is recommended that children with chronic intestinal failure be referred for assessment early, before liver dysfunction is established.

Management of end-stage central venous access in children referred for possible small bowel transplantation.

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.

Renal function following liver transplantation for unresectable hepatoblastoma

Abstract: 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 Childrens 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 Schwartzs formula. Twelve children with HB (mean age of diagnosis 33u2003months) who underwent LT (mean age 47u2003months) and 36 controls (mean age of LT 34u2003months) were studied. CsA was the main immunosuppressive drug used in each group. The median eGFR before, and at 3, 6, 12, 24 and 36u2003months 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. 90u2003mL/min/1.73u2003m2, respectively; 0.01u200a<u200apu200a<u200a0.03). The reductions in the median eGFR of both the HB group and controls before and at 36u2003months after LT were 49 and 41%, respectively. At 36u2003months 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 36u2003months after LT.

Bile bilirubin pigment analysis in disorders of bilirubin metabolism in early infancy

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 Childrens 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 Gilberts 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 Gilberts 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.

Social circumstances and medical complications in children with intestinal failure

Although most children discharged on home parenteral nutrition (HPN) will achieve enteral autonomy, some remain parenteral nutrition dependent; those who develop life-threatening complications may undergo small bowel transplantation (SBTx). The aim of this study was to investigate the relationship between social circumstances, compliance and complications. Subjects and methods An observational study in 2008–2012 on 64 children (34 HPN, 30 SBTx) from three units (two regional gastroenterology; one transplant). Social circumstances were assessed routinely as part of discharge planning; adherence by families to home care management was scored, and episodes of catheter-related blood stream infection and graft rejection were recorded for 2u2005years and related to compliance and social circumstances. Results A quarter of families had a disadvantaged parent: non-English speaking (n=11), unable to read (n=5), physical disability (n=3), mental health problems disclosed (n=10); 20% children were cared for by a lone parent. Discharge home was delayed by social factors (n=9) and need for rehousing (n=17, 27%). 17/34 (50%) of HPN and 12/30 (40%) of transplant families were assessed as fully adherent. 10 families were assessed as non-adherent, eight were subject to child protection review and care was taken over by another family member (n=3) or foster parents (n=2). The risk of catheter-related blood stream infection was increased by parental disadvantage and age <3u2005years (p<0.05). Poor compliance was associated with complications in HPN and SBTx recipients. Conclusions Children receiving complex home care may be socially isolated and measures to support improved compliance such as increased community support, social care involvement and respite care may improve outcomes.

Immunosuppression in infants with short bowel syndrome undergoing isolated liver transplantation

Abstract:u2002 Background:u2002 Little data exist on immunosuppressive drug absorption in children with short bowel syndrome and intestinal failure associated liver disease (SBS‐IFALD).

Severe intestinal lymphangiectasia complicated by nephrotic syndrome treated by small bowel, liver, and kidney transplantation.

A girl aged 2 years was examined for a 4-week history of periorbital edema, ankle swelling, and lethargy. Plasma albumin concentration was 13 g/L, with hypogammaglobulinemia (immunoglobulin G [IgG] 0.4 g/L), lymphopenia, and neutropenia (total leukocyte count, 1.3 ×10/L). Lymphocyte subsets indicated severe T-cell depletion with a CD3 count of 5 × 10 (normal count, 500 × 10). Regular immunoglobulin infusions and prophylactic antibiotics were prescribed. Twenty-four–hour urinary protein excretion was normal, but fecal 1antitrypsin levels were elevated at 29.0 g/dL (2 g/dL upper limit of normal), indicating a protein-losing enteropathy (PLE). Lymphangiography demonstrated normal distal intestinal lymphatics. Results of antigliadin, autoantibody screen, and sweat test were negative, and a jejunal biopsy showed dilated intestinal lymphatics. There were no positive isolates from multiple stool microscopy and cultures.

Hepatopulmonary syndrome in children – a 20 year review of presenting symptoms, clinical progression and transplant outcome

Hepatopulmonary syndrome (HPS) in stable patients with cirrhosis can easily be overlooked. We report on the presenting symptoms, disease progression, and outcomes after liver transplantation (LT) in children with HPS. Twenty patients were diagnosed with HPS between 1996 and 2016. The etiologies were as follows: biliary atresia (n = 9); alpha‐1‐antitrypsin deficiency (n = 2); cryptogenic liver disease (n = 3); and others (n = 6). HPS presentations were as follows; dyspnea (n = 17) and pneumonia (n = 3). For diagnostic confirmation, the following techniques were used: technetium‐99m‐labeled macroaggregated albumin lung perfusion scan (n = 13) or contrast echocardiogram (n = 7). There were 16 patients listed for LT, with a median age at HPS diagnosis of 10 years and an average wait from listing to LT of 9 weeks. A marked rise in hemoglobin (Hb; median, 125‐143.5 g/L) and modest decrease in oxygen saturation (SpO2; median 91% to 88% room air) were evident over this time. Patients’ need for assisted ventilation (1 day), pediatric intensive care unit (PICU) stay (3 days), and total hospital stay (20 days) were similar to our general LT recipients—the key difference in the postoperative period was the duration of supplementary O2 requirement. Hb of ≥130 g/L on the day of LT correlated with a longer PICU stay (P value = 0.02), duration of supplementary O2 (P value = 0.005), and the need for the latter beyond 7 days after LT (P value = 0.01). Fifteen patients had resolution of their HPS after LT. The 5‐, 10‐, and 20‐year survival rates were unchanged at 87.5%. None had a recurrence of HPS. In conclusion, HPS is a life‐threatening complication of cirrhosis which usually develops insidiously. This combined with the often‐stable nature of the liver disease leads to delays in diagnosis and listing for LT. Progressive polycythemia extends the need for supplementary O2 and PICU stay. We advocate screening for HPS with a combination of SpO2 and Hb monitoring to facilitate earlier recognition, timely LT, and shortened recovery periods.