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.

Social circumstances and medical complications in children with intestinal failure.

UNLABELLED: 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 2 years 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 <3 years (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.

A comparison of two validated scores for estimating risk of mortality of children with intestinal failure associated liver disease and those with liver disease awaiting transplantation.

BACKGROUND AND AIMS: To evaluate risk of mortality in children with intestinal failure associated liver disease (IFALD) compared with other liver disease using two validated scores. METHODS: Sixty-seven children listed for transplant were studied: cholestatic liver disease (CLDn23); liver disease secondary to other processes (LDsec n11); (IFALDn22), acute liver failure (ALFn11). Paediatric Hepatology Score (PHD) score and Pediatric end-stage liver disease score (PELD) were evaluated by Receiver Operating Curves (ROC), proportional hazards regression. RESULTS: The highest PHD and PELD scores were found in ALF; the lowest in LDsec. Both scores correlated well in identifying waiting list (WL) mortality in patients with CLD and ALF, but not in those with IFALD where PELD scores were lower. Cox proportional hazard regression of time spent on the waiting list prior to death or transplant/delisting showed significant associations with PHD (P=0.006) and PELD (P=0.008). WL mortality was strongly predicted by disease group (6/8 deaths in IFALD). ROC analysis of all data showed that a PHD score greater than 15.5 had sensitivity of 87.5% and specificity of 81% for waiting list mortality (P<0.001); PELD greater than 8 had a sensitivity of 87.5% and specificity of 40%. Neither PHD nor PELD scores correlated with post-transplant mortality. CONCLUSION: PHD and PELD scores had the same sensitivity for identifying risk of WL mortality in all patients, but PELD failed to identify the sickest children with IFALD, lowering its specificity. The PHD score has the added advantage for European centres of being in SI units, not requiring a computer application to calculate and was simpler to use at bedside.

Surgical complications after intestinal transplantation in infants and children--UK experience.

UNLABELLED: Surgical complications have a significant impact on morbidity and mortality following intestinal transplantation (ITx). Birmingham Children's Hospital commenced intestinal transplantation in 1993 and the following surgical strategies evolved: (a) pretransplant abdominal tissue expanders, 1998; (b) combined en-bloc reduced liver and intestinal transplantation (CRLITx), 1998; (c) staged abdominal closure, 2001; (d) preservation of graft duodenal artery, 2005. AIM: An internal audit was performed to document the surgical complications after ITx and to evaluate strategies in the management and prevention of complications. METHODS: A retrospective analysis of the medical records from January 1993 to June 2007 was conducted to identify surgical complications, evaluate management strategies, and report outcome following ITx. RESULTS: Forty-six children underwent 49 ITx (9 isolated intestinal, 39 combined liver and intestinal [CLITx], and 1 multivisceral transplant). Twenty three children had CRLITx since 1998, although there were none before 1997. The median donor: recipient weight ratio in CLITx was 2.2:1 (range, 0.67:1-6.70:1). Twenty-six children experienced 29 (59%) surgical complications: portacaval shunt thrombosis (n = 2, none alive); graft duodenal stump leakage (n = 3, 2 alive); spontaneous bowel perforation(n = 6, 2 alive); sub-acute bowel obstruction (n = 6, all alive); abdominal compartment syndrome ([ACS], n = 4, 2 alive); pancreatic leak (n = 3, 2 alive); biliary complications (n = 22, 17 alive ) failed staged abdominal closure with wound sepsis requiring skin grafting into the bowel (n = 1, alive), wound dehiscence (n = 1, alive), anastomotic leak (n = 1, alive) and intra-abdominal bleeding (n = 1,alive), primary nonfunction (n = 1, 1 died). Following the complications of ACS in children with primary abdominal closure and graft duodenal stump leaks in 2004, we modified our strategies in 2005 to include staged abdominal closure with recipient to donor weight mismatch, and preservation of the gastroduodenal artery during donor organ procurement in addition to pre transplant abdominal tissue expansion. Fifteen children with recipient and donor weight mismatch subsequently required staged closure of the abdomen and none of them developed ACS. Twelve children had gastroduodenal artery preserved and none developed graft duodenal stump leaks. Twenty-four of the 46 (52%) are alive 6 months to 10 years post transplant. CONCLUSION: Evolving strategies may avoid or reduce surgical complications commonly seen after intestinal transplantation and thus contribute to an improved outcome.

Impact of change in the United Kingdom pediatric donor organ allocation policy for intestinal transplantation.

BACKGROUND: Graft availability remains a problem in pediatric intestinal transplantation (IT), with most children waiting being less than 10 kg weight. In November 2004, wait-listed children in the United Kingdom were prioritized nationally to receive pediatric donor organs to improve donor availability for IT. We aimed to evaluate the impact of this change on the recipient population. METHODS: Data regarding pediatric donor organ availability and allocation were accessed from the National Transplant database. Recipient demographics and outcomes were recorded from the Liver Unit database. Between 2001 and 2006, there were 228 pediatric donors in the United Kingdom (nonheart-beating donors were excluded), of which 39 livers were allocated to emergency super-urgent liver candidates. A total of six isolated intestine and 21 liver-intestine transplants (15 reduced size, six full grafts) were performed in the same period. RESULTS: Since January 2001, there has been a progressive reduction in overall pediatric organ donation. Increasing awareness about IT has resulted in a significant increase in number of small bowel organs being offered (71.8% vs. 19.5%), although this has been associated with an increase in referrals for transplantation. Despite an increase in number of IT being performed (2.6 vs. 7.7 mean transplants per year), waiting list mortality still remains high in smaller children (<10 kg weight). No mortality was observed in larger children and in candidates for isolated IT. CONCLUSIONS: The new prioritization of the national pediatric donor allocation favoring IT has resulted in an increased number of procedures, without an impact on waiting list mortality for small children.

Update on intestinal rehabilitation after intestinal transplantation.

PURPOSE OF REVIEW: The past decade has seen improvements in patient selection and a greater range of surgical procedures available to patients with intestinal failure, and this, combined with more effective immunosuppressive regimens, has transformed survival after intestinal transplantation (ITx). Much more is known about optimizing rehabilitation of the engrafted intestine in the first 12 months after transplant, but it is also becoming apparent that there are some long-term health issues to consider. RECENT FINDINGS: The key issues in rehabilitation of ITx are the immunogenic nature of the intestinal graft, which means a higher risk of rejection and necessitates relatively high levels of immune suppression that promotes infections, including Epstein-Barr virus-driven lymphoma, viral gastroenteritis and renal impairment; and those related to the specifics of an intestinal allograft (nutritional support, chylous ascites, growth, food allergy, fat soluble vitamin deficiencies, metabolic bone disease). In this article, recent publications about approaches for establishing nutrition and methods for monitoring the health of the ITx patient are reviewed. SUMMARY: ITx appears to be cost-effective compared with parenteral nutrition, but ITx recipients continue to be vulnerable to infections, nutritional deficiencies and rejection over the long-term and, therefore, require support from and involvement of a multidisciplinary team for patients to become safely integrated with their local community.

Improved outcome of referrals for intestinal transplantation in the UK.

AIM: To describe the outcome of children with intestinal failure referred to Birmingham Children's Hospital (BCH) for consideration of intestinal transplantation (ITx), to determine factors for an adverse outcome and to analyse the impact of post-1998 strategies on survival. SUBJECTS AND METHODS: A retrospective analysis was performed of children referred for ITx assessment from January 1989 to December 2003. Children were assessed by a multidisciplinary team and categorised into: (a) stable on parenteral nutrition; (b) unsuitable for transplantation (Tx); and (c) recommended for Tx. To analyse the impact of the post-1998 strategies on survival, a comparison was made between the two eras (pre-1998 and post-1998). RESULTS: 152 children with chronic intestinal failure were identified (63M:89F, median age 10 months (range 1-170)). After assessment, 69 children were considered stable on parenteral nutrition (5-year survival 95%); 28 children were unsuitable for Tx (5-year survival 4%); and 55 children were recommended for Tx (5-year survival 35%, which includes 14 children who died waiting for size-matched organs). Twenty three ITx and nine isolated liver transplants (iLTx) were performed. In a multivariate analysis, the following factors in combination had an adverse effect on survival: the presence of a primary mucosal disorder (p = 0.007, OR ratio 3.16, 95% CI 1.37 to 7.31); absence of involvement of a nutritional care team at the referring hospital (p = 0.001, OR ratio 2.55, 95% CI 1.44 to 4.52); and a serum bilirubin>100 micromol/l (p = 0.001, OR ratio 3.70, 95% CI 1.84 to 7.47). Earlier referral (median serum bilirubin 78 micromol/l in the post-1998 era compared with 237 micromol/l in the pre-1998 era, p = 0.001) may be a contributory factor to improved survival. The strategies of combined en bloc reduced liver/small bowel transplantation and iLTx resulted in fewer deaths on the waiting list in the post-1998 era (2 deaths in post-1998 era v 12 deaths in pre-1998 era). The overall 3-year survival in the post-1998 era (69%) has improved compared with the pre-1998 era (31%; p<0.001) CONCLUSION: The changing characteristics at the time of referral, including earlier referral and innovative surgical strategies have resulted in improved long-term survival of children referred for ITx.

Immunosuppression in infants with short bowel syndrome undergoing isolated liver transplantation.

BACKGROUND: Little data exist on immunosuppressive drug absorption in children with short bowel syndrome and intestinal failure associated liver disease (SBS-IFALD). AIM: To evaluate the absorption of immunosuppressive medications in children with SBS-IFALD undergoing isolated liver transplantation (iLTx). METHODS: A retrospective review was performed in children with SBS-IFALD undergoing LTx and comparison made with weight, age-matched children undergoing iLTX (extra-hepatic biliary atresia (EHBA) and normal intestinal length and function). RESULTS: Seven children with SBS-IFALD undergoing iLTx (median residual bowel length, 60 cm, range 40-80) were compared with 15 children undergoing LTx for EHBA. SBS-IFALD children had significantly lower trough tacrolimus levels at three months (5.8 vs. 7.9 ng/mL, p<0.05) and six months (5.0 vs. 8.0 ng/mL, p<0.05), but equivalent levels at 12 months after iLTx. The median calculated dose-normalized concentrations indicated that systemic availability of tacrolimus was comparable in two groups at 3, 6, 12 months (33.1 vs. 23.3; 42.4 vs. 36; 51 vs. 52.9) despite the differences in enteral function. The incidence of acute rejection was 1/7 (SBS-IFALD) and 10/15 (EHBA) group (p = 0.06). CONCLUSION: Children with SBS-IFALD demonstrated adequate absorption of oral tacrolimus without significant acute rejection rate after iLTx suggesting that modification of immunosuppression is not necessary.

A prospective study of endoscopic esophageal variceal ligation using a multiband ligator.

BACKGROUND: Endoscopic variceal band ligation (EVL) is the preferred method of treating variceal hemorrhage in adults. The need to reinsert the endoscope after reloading for each varix ligation has been a drawback. The Saeed multiband ligator allows ligation of multiple varices during a single insertion. The multibander has not been used previously in children. METHODS: Twenty-eight consecutive children were referred to a pediatric liver unit because of esophageal variceal bleeding from 1998 to 2000. Endoscopic variceal band ligation was performed at initial endoscopy and repeated monthly until varices were obliterated or were too small to ligate. RESULTS: Results are expressed as median (range). Age at EVL was 11 years (3 months to 16 years) and weight 30 kg (5.4-63 kg). Portal hypertension was caused by cirrhosis in 15 children. Endoscopic variceal band ligation was performed on 66 occasions with 4 bands applied per session. Ten children had active bleeding at initial endoscopy and all responded to EVL. Interval bleeding developed in 2 children before variceal ablation. Varices were obliterated in 26 of 28 patients after 2 sessions. During the 21-month follow-up (2 months to 3 years), six children have undergone elective liver transplantation and three have had mesoportal bypass procedures. Rebleeding developed in 2 of 26; 1 from recurrent esophageal varices that responded to repeat EVL and 1 from gastric varices. Following variceal ablation, 2-year actuarial variceal recurrence risk was 40%. CONCLUSIONS: Endoscopic variceal ligation is highly effective in obliterating esophageal varices in children. The use of a multibander device for endoscopic variceal ligation is technically feasible and safe even in small children, and its use results in more rapid ablation of esophageal varices.