Intestinal Atp8b1 dysfunction causes hepatic choline deficiency and steatohepatitis.

Choline is an essential nutrient, and its deficiency causes steatohepatitis. Dietary phosphatidylcholine (PC) is digested into lysoPC (LPC), glycerophosphocholine, and choline in the intestinal lumen and is the primary source of systemic choline. However, the major PC metabolites absorbed in the intestinal tract remain unidentified. ATP8B1 is a P4-ATPase phospholipid flippase expressed in the apical membrane of the epithelium. Here, we use intestinal epithelial cell (IEC)-specific Atp8b1-knockout (Atp8b1IEC-KO) mice. These mice progress to steatohepatitis by 4 weeks. Metabolomic analysis and cell-based assays show that loss of Atp8b1 in IEC causes LPC malabsorption and thereby hepatic choline deficiency. Feeding choline-supplemented diets to lactating mice achieves complete recovery from steatohepatitis in Atp8b1IEC-KO mice. Analysis of samples from pediatric patients with ATP8B1 deficiency suggests its translational potential. This study indicates that Atp8b1 regulates hepatic choline levels through intestinal LPC absorption, encouraging the evaluation of choline supplementation therapy for steatohepatitis caused by ATP8B1 dysfunction.

Hungry Bone Syndrome After Living Donor Liver Transplant for Biliary Atresia.

Hungry bone syndrome is a rare but potentially lethal complication that is characterized by rapid, severe, long-lasting hypocalcemia and hypophosphatemia secondary to increased bone metabolism. We present a case of hungry bone syndrome after living donor liver transplant for biliary atresia. Following a failed Kasai procedure for biliary atresia, a 5-month-old boy underwent living donor liver transplant with reduced left lateral lobe from his father. Despite the oral administration of alfacalcidol, the patient exhibited severe craniotabes before the surgery. He developed severe hypocalcemia and hypophosphatemia im-mediately after liver transplant and required supplementation of calcium and phosphorus for 1 month thereafter. After serum levels of calcium and phosphate had normalized, there was a rapid increase in the serum bone-type alkaline phosphatase level, and the craniotabes subsided remarkably. To our knowledge, this is the world's first reported case of hungry bone syndrome after liver transplant for cholestatic cirrhosis. It underscores the importance of strict nutritional and electrolyte management in the perioperative period. A prompt diagnosis and correction of hungry bone syndrome are imperative to prevent the associated significant morbidity and mortality.

Living-donor liver transplantation for propionic acidemia.

Propionic acidemia is a rare autosomal recessive disorder affecting the catabolism of branched-chain amino acids because of a genetic defect in PCC. Despite the improvements in medical treatment with protein restriction, sufficient caloric intake, supplementation of l-carnitine, and metronidazole, patients with the severe form of propionic acidemia have life-threatening metabolic acidosis, hyperammonemia, and cardiomyopathy, which results in serious neurologic sequelae and sometimes death. This study retrospectively reviewed three children with neonatal-onset propionic acidemia who received LDLT. Between November 2005 and December 2010, 148 children underwent LDLT, with an overall patient survival of 90.5%, in our center. Three patients were indicated for transplantation because of propionic acidemia. All recipients achieved a resolution of metabolic derangement and better quality of life with protein restriction and medication, although urine methylcitrate and serum propionylcarnitine levels did not decrease markedly. LT can reduce the magnitude of progressive cardiac/neurologic disability as a result of poor metabolic control. Further evaluation is therefore required to determine the long-term suitability of this treatment modality.