Objective. Transplantation of isolated hepatocytes in animal models has been shown to correct inborn errors of metabolism. Based on these studies and our experience with hepatocyte transplantation in a child with Crigler-Najjar syndrome, isolated hepatocyte transplantation was performed to attempt metabolic reconstitution in a male infant with severe ornithine transcarbamylase (OTC) deficiency. Methods. An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hyperammonemia. Isolated hepatocytes were obtained by collagenase perfusion of donated livers not used for transplantation. Hepatocytes were infused in batches over the first 4 weeks of life via an umbilical venous catheter positioned in the portal vein. Immunosuppression consisted of tacrolimus and corticosteroids. Results. Over 4 billion viable hepatocytes were transplanted during the first 3.5 weeks of life. A period of metabolic stability was achieved between days 20 and 31 during which normal protein intake was tolerated while phenylbutyrate was weaned. During this time, plasma ammonia and glutamine remained within normal limits. Hyperammonemia reappeared abruptly on day 31 of life. Protein tolerance diminished to baseline; metabolic stability was subsequently reattained only following successful liver transplantation at 6 months of age. Conclusions. Isolated hepatocyte transplantation appeared to result in temporary relief of hyperammonemia and protein intolerance attributable to OTC deficiency. The metabolic stability achieved was lost after 11 days presumably because of rejection of the transplanted cells because of insufficient immunosuppression. Future attempts at isolated hepatocyte transplantation for inborn errors of metabolism in humans should include adequate immunosuppression and a liver biopsy as a means of proving hepatocyte engraftment and function.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of -41% and -45%, respectively, with 0.025 mg/kg/d teduglutide and by -25% and -52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and -6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and -1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF. ClinicalTrials.gov:NCT01952080; EudraCT: 2013-004588-30.