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Hepatocellular adenomas (HAs) are tumors that can develop under different conditions, including in patients harboring a germline mutation in HNF1A. However, little is known about the pathogenesis of such disease. This work aims to better define what mechanisms lie under the development of this condition. Six HAs were sampled from the liver of a 17-year-old male affected by diabetes and multiple hepatic adenomatosis harboring the heterozygous pathogenic germline variant c.815G>A, p.(Arg272His) in HNF1A, which has a dominant negative effect. All HAs were molecularly characterized. Four of them were shown to harbor a second somatic HNF1A variant and one had a mutation in the ARID1A gene, while no additional somatic changes were found in the remaining HA and normal parenchyma. A transcriptomic profile of the same HA samples was also performed. HNF1A biallelic mutations were associated with the up-regulation of several pathways including the tricarboxylic acid cycle, the metabolism of fatty acids, and mTOR signaling while angiogenesis, endothelial and vascular proliferation, cell migration/adhesion, and immune response were down-regulated. Contrariwise, in the tumor harboring the ARID1A variant, angiogenesis was up-modulated while fatty acid metabolism was down-modulated. Histological analyses confirmed the molecular data. Independently of the second mutation, energetic processes and cholesterol metabolism were up-modulated, while the immune response was down-modulated. This work provides a complete molecular signature of HNF1A-associated HAs, analyzing the association between specific HNF1A variants and the development of HA while identifying potential new therapeutic targets for non-surgical treatment.

Intestinal graft-versus-host disease (I-GvHD) represents a life-threatening complication in allogeneic stem cell transplantation (SCT). Unfortunately, non-invasive validated diagnostic tools to diagnose I-GvHD, evaluate treatment response, and guide the duration of immunosuppression are still lacking. We employed standard ultrasound and power Doppler to diagnose and follow up on pediatric intestinal GvHD. We herein report on three patients, prospectively evaluated among 24 pediatric patients referred to our center for allogeneic SCT. These three patients presented abdominal pain and diarrhea within the first 200 days after transplantation. In the reported cases, we performed small- and large-intestine ultrasound (US) at clinical onset of lower-intestinal symptoms and, when intestinal GvHD was confirmed, at GvHD flares, if any, and at follow-up. US constantly (3/3 patients) revealed increased bowel wall thickening (BWT) with different bowel segments’ involvement from patient to patient. Further, a moderate or strong increased Doppler signaling was seen in 2 out of 3 patients, according to clinical GVHD staging (e.g., the more the increase, the more the staging). Standard sonography corroborated GvHD diagnosis in all patients considered and was able to detect GvHD progression or complete normalization of findings, thus simplifying ensuing clinical decisions. Our report highlights the need to design clinical trials for the validation of non-invasive radiologic tools for diagnosis and follow-up of GvHD, especially in pediatric patients.

Italy was one of the first industrialized countries to implement a program of routine vaccination against hepatitis B virus (HBV) infection. However, currently, no HBV vaccine is administered at birth if the screened mother is HBsAg negative, whilst babies born to HBsAg positive mothers are given vaccine and hepatitis B immunoglobulin, within 12–24 post-delivery hours. A single center retrospective analysis of policies and practices to prevent mother-to-child transmission of HBV was carried out, to evaluate their adherence to HBV care guidelines. Paired maternal-infant medical records for consecutive live births, between January 2015 and December 2019, were reviewed at the AOU Città della Salute e Scienza di Torino, where a total of 235/35,506 babies (0.7%) were born to HBsAg positive mothers. Markers of active viral replication, i.e., HBV DNA level and/or HBeAg, were reported in only 66/235 (28%) of the mothers’ medical records. All newborns had immunoprophylaxis at birth: 61% at 36 h. In 2019, two cases of vertical HBV transmission occurred, despite timely immunoprophylaxis, as their mothers’ viral load was detected too late for antiviral prophylaxis. Missed early identification of pregnant women with high viremia levels or late vaccinations may contribute to perinatal HBV infection. Immunoprophylaxis should be given to babies born to HBsAg positive mothers at the latest within 12 h. In Italy, policies aimed at achieving the WHO 2030 goal of eliminating viral hepatitis should be further implemented.