Acute disseminated encephalomyelitis will often present to the general paediatrician as an acute polysymptomatic encephalopathy, and initially the diagnosis may not be clear. A brain MRI scan is essential in establishing the diagnosis and so enabling appropriate advice and treatment to be given. Multicentre clinical audit of outcome and controlled therapeutic trials are needed to secure an evidence base for current practice.

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.

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 µmol/l (p = 0.001, OR ratio 3.70, 95% CI 1.84 to 7.47). Earlier referral (median serum bilirubin 78 µmol/l in the post-1998 era compared with 237 µmol/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.

Background: Mitochondrial liver disease (MLD), and in particular mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an important cause of acute liver failure (ALF) in infancy. Early and accurate diagnosis is important because liver transplantation (LT) is often contraindicated. It is unclear which methods are the best to diagnose MLD in the setting of ALF.Objective: The aim of the study was to determine the incidence of MLD in children younger than 2 years with ALF and the utility of routine investigations to detect MLD.Methods: Thirty‐nine consecutive infants with ALF were admitted to a single unit from 2009 to 2011. All were extensively investigated using an established protocol. Genes implicated in mitochondrial DNA depletion syndrome were sequenced in all cases and tissue mtDNA copy number measured where available.Results: Five infants (17%) had genetically proven MLD: DGUOK (n = 2), POLG (n = 2), and MPV17 (1). Four of these died, whereas 1 recovered. Two had normal muscle mtDNA copy number and 3 had normal muscle respiratory chain enzymes. An additional 8 children had low hepatic mtDNA copy number but pathogenic mutations were not detected. One of these developed fatal multisystemic disease after LT, whereas 5 who survived remain well without evidence of multisystemic disease up to 6 years later. Magnetic resonance spectroscopy did not distinguish between those with and without MLD.Conclusions: Low liver mtDNA copy number may be a secondary phenomenon in ALF.Screening for mtDNA maintenance gene mutations may be the most efficient way to confirm MLD in ALF in the first 2 years of life.

PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22–24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0–4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22–24 of PEDFIC 2 in sBAs was -201 μmol/L (p <0.0001). For cohort 1B and cohort 2, mean changes from odevixibat initiation to weeks 22–24 in sBAs were -144 and -104 μmol/L, respectively. The proportion of positive pruritus assessments in the first 24-week period of PEDFIC 2 was 33%, 56%, and 62% in cohorts 1A, 1B, and 2, respectively. Most TEAEs were mild or moderate. No drug-related serious TEAEs occurred. Odevixibat in patients with progressive familial intrahepatic cholestasis was generally well tolerated and associated with sustained reductions in sBAs and pruritus. This study is registered at ClinicalTrials.gov (NCT03659916). Disrupted bile flow is a hallmark feature of patients with progressive familial intrahepatic cholestasis and can result in build-up of bile constituents in the liver with spill over into the bloodstream; other effects that patients can experience include extremely itchy skin, and because not enough bile reaches the gut, patients can have problems digesting food, which may lead to poor growth. Odevixibat is an orally administered medication that shunts bile acids away from the liver. The current study, called PEDFIC 2, suggested that odevixibat can improve the problematic signs and symptoms of progressive familial intrahepatic cholestasis and was generally safe for patients.