Hepatitis D in Children.

Hepatitis D virus (HDV) is an uncommon, defective, single-stranded circular RNA virus that is dependent on the hepatitis B virus' surface antigen envelope proteins for transmission. It is highly pathogenic and associated with high rates of progression to cirrhosis and associated complications. HDV continues to ravage endemic parts of Asia and Europe, and its prevalence in the United States, although low, has not decreased in frequency, despite universal hepatitis B virus vaccination, because of lack of testing and underrecognition. There are few reports on the prevalence and characteristics of HDV infection in the pediatric population. We present 2 patients with HDV infection at our institution; both were from eastern Europe and were treated with pegylated interferon-α. The present standard of care treatment for HDV yields suboptimal results, but insights into the virology of hepatitis D are stimulating the search for novel therapeutic approaches, particularly the development of prenylation inhibitors and viral entry inhibitors.

Angiosarcoma successfully treated with liver transplantation and sirolimus.

Malignant liver tumors represent approximately 1% of malignancies in children. HA is a high-grade tumor of endothelial cells that is even more rare in the pediatric population. HA has a limited response to chemotherapy, radiation and resection with universal tumor recurrence with LT and nearly 100% mortality by 18 months. This is the first reported successful case of hepatic angiosarcoma in a child who was treated by LT in combination with sirolimus. Sirolimus antagonizes the mTOR pathway, which regulates cell proliferation, differentiation, and migration, and is being studied as an anti-neoplastic agent for solid tumors.

MyD88 controls human metapneumovirus-induced pulmonary immune responses and disease pathogenesis.

Human metapneumovirus (hMPV) is a common cause of lung and airway infections in infants and young children. Recently, we and others have shown that hMPV infection induces Toll-like receptor (TLR)-dependent cellular signaling. However, the contribution of TLR-mediated signaling in host defenses against pulmonary hMPV infection and associated disease pathogenesis has not been elucidated. In this study, mice deficient in MyD88, a common adaptor of TLRs, was used to investigate the contribution of TLRs to in vivo pulmonary response to hMPV infection. MyD88(-/-) mice have significantly reduced pulmonary inflammation and associated disease compared with wild-type (WT) C57BL/6 mice after intranasal infection with hMPV. hMPV-induced cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and isolated lung conventional dendritic cells (cDC) are also significantly impaired by MyD88 deletion. In addition, we found that MyD88 is required for the recruitment of DC, T cells, and other immune cells to the lungs, and for the functional regulation of DC and T cells in response to hMPV infection. Taken together, our data indicate that MyD88-mediated pathways are essential for the pulmonary immune and pathogenic responses to this viral pathogen.