Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases

n/

Clinico-pathological features of liver disease following paediatric bone marrow transplantation

Objectives: The knowledge on clinico-pathological features of liver injury following paediatric bone marrow transplantation (BMT), including liver graft versus host disease (L-GVHD), is scarce. Previous studies showed that the main target of hepatic damage is the biliary tract. We aimed to describe the features of bile duct injury in a cohort of children who consecutively underwent BMT for haematological disorders, and correlate them to clinical signs of liver disease. Methods: from 2013 to 2015 protocol biopsies were scheduled for every child listed for BMT at our haemato-oncology unit. All patients showing significant clinical and/or histological liver disease were scheduled for follow up biopsies. Histology samples were reviewed and scored according to a previously reported semi-quantitative system1, and compared with liver function tests (ALT, GGT, bilirubin, serum bile acid). Features of bile duct disease (ductular proliferation, biliary metaplasia, bile duct atrophy and ductopenia) were also reported separately. Ductopenia (bile duct to portal tract ratio <0.5) was evaluated on cytokeratin 7 stained histology slices. Overt L-GVHD was diagnosed when clinical cholestatic disease and histology consistent with GVHD were present, after exclusion of other causes. Results: 50 BMTs in 44 patients (28 males, mean age 9.3 years) were carried out in the study period; overall 97 liver biopsies were performed and 89 were available for review; 45 patients had one, 30 had two, 15 had three and 5 had 4 liver biopsies taken following BMT. The mean L-GVHD score was 6.3, 5.8, 5.6 and 4.6 at the respective number of serial biopsies taken during the follow up. Bile duct proliferation was diagnosed in 81/89 (91%), metaplasia in 33/89 (37%), atrophy in 72/89 (81%). Ductopenia was diagnosed in 83/89 samples (93%), and was persisting in 11/27, worsening in 16/27 pts who had a second biopsy. Ductopenia, bile duct proliferation and atrophy were the main features in all patients who had three or four follow up biopsies, whereas metaplasia tended to disappear. Over a mean follow up of 1.4 years (SD \ub10.7), 16 patients (32%) developed overt L-GVHD, 9 died of systemic complications and 7 are alive, 4 of whom with liver disease. All the other patients, at the last follow up, have normal liver tests. Conclusion: Ductopenia is found in almost all children undergoing a liver biopsy following BMT, is persisting and often accompanied by ductular proliferation and atrophy. The clinico-pathological correlation, though, reveal that only a minority of such patients develops a clinical liver disease which, when fully expressed, is associated with a poor prognosis

Biliary cystadenoma with bile duct communication depicted on liver-specific contrast agent-enhanced MRI in a child

Biliary cystadenoma is a benign, but potentially malignant, cystic neoplasm of the biliary ducts occurring most commonly in middle-aged females and very rarely in children. We present a 9-year-old boy with biliary cystadenoma, diagnosed by MRI using a new liver-specific contrast agent (gadoxetic acid) that is eliminated by the biliary system. The images clearly demonstrate the communication between the multiloculated cystic mass and the biliary tree, suggesting the possibility of biliary cystadenoma. Due to the malignant potential of a cystadenoma, the lesion was resected. The resection was complete and the postoperative course was uneventful. © 2010 Springer-Verlag

Vanishing Bile Ducts in the Long Term after Pediatric Hematopoietic Stem Cell Transplantation

Abstract There are no structured studies on liver histology after hematopoietic stem cell transplantation (HSCT). We aimed to prospectively describe the clinicopathologic features of liver disease in the long term after HSCT in an observational, longitudinal study of liver histology in a consecutive cohort of children undergoing allogeneic HSCT. First liver biopsy was performed in presence of abnormal liver function tests and repeated per protocol thereafter. A previously reported semiquantitative score evaluating inflammation, cholestasis, and ductopenia (bile ducts-to-portal tracts ratio ≤ .5) was adopted. Graft-versus-host disease (GVHD) was diagnosed according to standard criteria. We evaluated 131 biopsies taken in 50 HSCTs performed in 47 children (mean age, 9.7 ± 5.2 years). Pre-HSCT chemotherapy was administered in 36 of 50 (72%). GVHD was diagnosed in 17 of 50 (34%). Over time the overall score decreased from a mean of 6 ± 2.7 to 3.25 ± .96 (P Vanishing bile duct syndrome after HSCT may be due to drug-induced liver disease. Longer follow-up will reveal whether these patients are prone to late liver-related morbidity and mortality

Treatment with an ileal bile acid transporter inhibitor in patients with TJP2 deficiency

There are no published data on the use of odevixibat, a selective ileal bile acid transporter (IBAT) inhibitor, in children with tight junction protein 2 (TJP2) deficiency (also named as PFIC-4). We describe a case series of five children treated with odevixibat. After treatment, serum bile acids (sBA) decreased compared to baseline [mean value: 244 (+/- 125), vs 38 (+/- 34) mu mol/L; p -- 0.007]; reduction in sBA was &gt;70% from baseline (or &lt;70 mu mol/L) in all. Improvements in pruritus were reported in all patients. The drug was well tolerated. IBAT inhibitors should be considered a valuable treatment option in patients with TJP2 deficiency

Acute Neurological Involvement after Donor Lymphocyte Infusion for Post-Transplant Viral Infection: The Same Pattern of Novel Cancer Immunotherapy-Related CNS Toxicity?

Early post-transplant is the critical phase for the success of hematopoietic stem cell transplantation (HSCT). New viral infections and the reactivations associated with complete ablation of the recipient’s T-cell immunity and inefficient reconstitution of the donor-derived system represent the main risks of HSCT. To date, the pharmacological treatments for post-HSCT viral infection-related complications have many limitations. Adoptive cell therapy (ACT) represents a new pharmacological strategy, allowing us to reconstitute the immune response to infectious agents in the post-HSC period. To demonstrate the potential advantage of this novel immunotherapy strategy, we report three cases of pediatric patients and the respective central nervous system complications after donor lymphocyte infusion

Inflammatory fibroid polyps in children: A new case report and a systematic review of the pediatric literature

To study that inflammatory fibroid polyps (IFPs) in children are extremely uncommon tumors that may occur throughout the gastrointestinal tract