Targeting plasma cells with daratumumab aids in the treatment of post-transplant autoimmune-like hepatitis.

Antibody-mediated autoimmune-like hepatitis is a rare and challenging occurrence after hematopoietic cell transplant (HCT). We present the case of a 16-year-old male patient with Ph+ ALL who underwent matched sibling donor HCT and developed autoimmune-like hepatitis after receiving ponatinib for post-HCT maintenance, evidenced by marked plasma cell infiltrate on liver biopsy. He was successfully treated with steroids and daratumumab, an anti-CD38-monoclonal antibody. The dramatic response in this patient warrants expanded investigation of daratumumab for plasma cell-mediated disorders post-HCT. It further highlights that identifying mechanisms of immune-mediated injury can allow for directed therapy and limit exposure to broad immune suppression.

Liver transplantation for acute Budd-Chiari syndrome in identical twin sisters with Factor V leiden mutation.

BACKGROUND: Budd-Chiari syndrome (BCS) is uncommon in the children. The cause of BCS comprises several diseases leading to thrombophilia. Activated protein C resistance as a result of a single gene mutation in factor V, the so called factor V Leiden (FVL), is the most common cause of thrombophilia. METHODS: We report a simultaneous occurrence of BCS in identical twin sisters of 13 years of age with heterozygous FVL mutation. RESULTS: One sister presented with acute BCS leading to fulminant hepatic failure. She underwent liver transplantation with subsequent normalization of activated protein C resistance. The other twin sister, who was diagnosed with extensive thromboses of the inferior vena cava, portal vein, and hepatic veins, was successfully managed by aggressive chemical and mechanical thrombolysis followed by therapeutic anticoagulation. Genomic DNA studies confirmed heterozygosity of FVL mutation in the sisters' father and older brother. CONCLUSIONS: The exact cause of the BCS in children should be thoroughly and rapidly investigated, and, if necessary, immediate family members should also be tested for genetic defects in factor V or concomitant thrombophilia.

Regulation of triacylglycerol and phospholipid trafficking by fatty acids in newborn swine enterocytes.

We (Wang H, Berschneider HM, Du J, and Black DD. Am J Physiol Gastrointest Liver Physiol 272: G935-G942, 1997; Wang H, Lu S, Du J, Yao Y, Berschneider HM, and Black DD. Am J Physiol Gastrointest Liver Physiol 280: G1137-G1144, 2001) previously showed that different fatty acids influence synthesis and secretion of triacylglycerol (TG) and phospholipid (PL) in a newborn swine enterocyte cell line (IPEC-1). The most striking effects were produced by stearic acid (SA; 18:0), which modestly affected TG and PL synthesis but reduced TG and PL secretion, and by eicosapentaenoic acid (EPA; 20:5), which reduced TG and PL synthesis and TG secretion relative to oleic acid (OA; 18:1). To define the mechanism of these effects, differentiated IPEC-1 cells were incubated for 24 h with OA, SA, or EPA and [(3)H]glycerol. Endoplasmic reticulum (ER) and Golgi (G) content of labeled lipids and apolipoprotein (apo) B and apoAI protein were measured. Relative to OA, SA did not impair ER TG synthesis, but reduced movement of labeled TG from ER to G. EPA impaired both ER TG synthesis and movement of labeled TG from ER to G. PL followed the same pattern, except ER synthesis of PL was relatively unaffected by EPA. Carbonate treatment demonstrated decreased partitioning of labeled lipid from ER membrane to lumen in EPA-treated cells. Organelle apoB and apoAI content demonstrated opposite patterns after SA and EPA incubation. We conclude that SA and EPA adversely influence immature enterocyte ER to G lipid trafficking, compared with OA. Furthermore, EPA inhibits ER lipid synthesis and transfer of membrane lipid to luminal particles. Regulation of apoAI ER to G trafficking is independent of that of apoB.