China ; Consensus ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hepatic Veno-Occlusive Disease/therapy* ; Humans ; Transplantation Conditioning

Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.
Animals ; Bile ; Bile Acids and Salts ; Endothelial Cells/metabolism* ; Hepatic Veno-Occlusive Disease/pathology* ; Inflammation/pathology* ; Liver Cirrhosis/drug therapy* ; Mice ; Powders ; Pyrrolizidine Alkaloids/adverse effects* ; Ursidae

Child ; Hepatic Veno-Occlusive Disease/etiology* ; Humans

Pediatric hepatobiliary imaging is important for evaluation of not only congenital or structural disease but also metabolic or diffuse parenchymal disease and tumors. A variety of ultrasonography and magnetic resonance imaging (MRI) techniques can be used for these assessments. In ultrasonography, conventional ultrasound imaging as well as vascular imaging, elastography, and contrast-enhanced ultrasonography can be used, while in MRI, fat quantification, T2/T2* mapping, diffusion-weighted imaging, magnetic resonance elastography, and dynamic contrast-enhanced MRI can be performed. These techniques may be helpful for evaluation of biliary atresia, hepatic fibrosis, nonalcoholic fatty liver disease, sinusoidal obstruction syndrome, and hepatic masses in children. In this review, we discuss each tool in the context of management of hepatobiliary disease in children, and cover various imaging techniques in the context of the relevant physics and their clinical applications for patient care.
Biliary Atresia ; Child ; Elasticity Imaging Techniques ; Fibrosis ; Hepatic Veno-Occlusive Disease ; Humans ; Liver ; Magnetic Resonance Imaging ; Non-alcoholic Fatty Liver Disease ; Patient Care ; Ultrasonography

PURPOSE: This study examined the effects of parenteral nutrition (PN) on the nutritional status, clinical improvement, and PN-related complications in pediatric patients who had undergone hematopoietic stem cell transplantation (HSCT). METHODS: A retrospective audit of 110 pediatric patients (age≤18), who underwent HSCT from March 2015 to February 2017 was undertaken. The patients were divided into 3 groups based on the ratio of daily calorie supplementation to the daily calorie requirement (ROCS). The clinical factors related to the nutritional status, such as difference in body weight (BW), body mass index (BMI), percent ideal body weight (PIBW), total protein (T.protein), and albumin; the early clinical outcome, such as PN-duration, length of hospitaliaztion (LOH), engraftment day (ED), graft-versus-host disease, sepsis, pneumonia and mucositis; and PN-related complications, including elevation of total bilirubin (T.bil), direct bilirubin (D.bil), aspartate aminotransferase, alanine aminotransferase, glucose and cholesterol levels, and hepatic veno-occlusive disease were analyzed using the electronic medical records. Additional analysis subject to auto-HSCT and allo-HSCT patients was also performed. RESULTS: The very-low-ROCS, low-ROCS, and satisfied-ROCS group were 30 (27.3%), 47 (42.7%), and 33 (30.0%) patients, respectively. The PN-duration (P=0.005, z=−2.271), LOH (P=0.023, z=−2.840), ED (P < 0.001, z=−3.695), T.bil elevation (P < 0.001, z=−3.660), and D.bil elevation (P=0.002, z=−3.064) tended to decrease with increasing ROCS. The difference in the PN-duration (P=0.017), ED (P=0.001), T.bil elevation (P=0.001), and D.bil elevation (P=0.011) in the 3 groups was statistically significant. In the auto-HSCT patients, the change in BW (P=0.031, z=+2.154), PIBW (P=0.029, z=+2.187), and BMI (P=0.021, z=+2.306) tended to increase. In the allo-HSCT patients, the change in T.protein (P=0.022, z=+2.286) increased but the ED (P=0.021, z=−2.304) decreased. CONCLUSION: Aggressive PN supplementation has an effect on maintaining the nutritional status and achieving better early outcomes in pediatric HSCT patients, whereas it has no effect on increasing the PN-related complications.
Alanine Transaminase ; Aspartate Aminotransferases ; Bilirubin ; Body Mass Index ; Body Weight ; Cholesterol ; Electronic Health Records ; Glucose ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Hepatic Veno-Occlusive Disease ; Humans ; Ideal Body Weight ; Mucositis ; Nutritional Status ; Parenteral Nutrition* ; Pediatrics ; Pneumonia ; Retrospective Studies ; Sepsis

With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT.
Adolescent* ; Astrocytoma ; Brain Neoplasms ; Carboplatin ; Child* ; Cyclophosphamide ; Drug Therapy* ; Etoposide ; Glioblastoma ; Glioma* ; Hepatic Veno-Occlusive Disease ; Humans ; Medical Records ; Melphalan ; Radiotherapy ; Retrospective Studies ; Stem Cell Transplantation* ; Stem Cells* ; Thiotepa

Although radiotherapy (RT) is used for the treatment of cancers, including liver cancer, radiation-induced liver disease (RILD) has emerged as a major limitation of RT. Radiation-induced toxicities in nontumorous liver tissues are associated with the development of numerous symptoms that may limit the course of therapy or have serious chronic side effects, including late fibrosis. Although the clinical characteristics of RILD patients have been relatively well described, the understanding of RILD pathogenesis has been hampered by a lack of reliable animal models for RILD. Despite efforts to develop suitable experimental animal models for RILD, current animal models rarely present hepatic veno-occlusive disease, the pathological hallmark of human RILD patients, resulting in highly variable results in RILD-related studies. Therefore, we introduce the concept and clinical characteristics of RILD and propose a feasible explanation for RILD pathogenesis. In addition, currently available animal models of RILD are reviewed, focusing on similarities with human RILD and clues to understanding the mechanisms of RILD progression. Based on these findings from RILD research, we present potential therapeutic strategies for RILD and prospects for future RILD studies. Therefore, this review helps broaden our understanding for developing effective treatment strategies for RILD.
Fibrosis ; Hepatic Veno-Occlusive Disease ; Humans ; Liver Diseases* ; Liver Neoplasms ; Liver* ; Models, Animal ; Radiotherapy

OBJECTIVETo evaluate the morbidity, risk factors, clinical characterisitics, treatments and prognosis of delayed hepatic veno-occlusive disease(HVOD) after haploidentical hematopoietic stem cell transplantation (hi-HSCT).

METHODSThe clinical data of 208 patients undergoing hi-HSCT were retrospectively analyzed.

RESULTSSix patients were diagnosed with delayed VOD, among them 4 patients were moderate VOD and 2 patients were severe VOD. The incidence of VOD after hi-HSCT was 2.88%, the median onset time was 44.5(30-57) days after transplant, 2 patients died of multiple organ failure (MOF) due to rapid progress of disease. With intravenous administration of defibrotide, 4 patients displayed encouraging response, but 2 patients died of hepatic acute graft-versus-host disease (aGVHD), 1 had bone marrow relapse and the other one was cured.

CONCLUSIONNorethindrone is one of the high risk factors, while sex, age and disease status are irrelevant to the occurrence of VOD. Unfractionated heparin (UH) can effectively decrease the morbidity. Pretransplant hepatic function reserve, high dose preconditioning regimens and pharmacotherapy may result in delayed VOD onset. The delayed VOD has the same clinical features and treatment-response as early VOD, but a poorer prognosis is usually observed. A larger amount of samples (patients) is needed to research the relationship of the delayed VOD with hi-HSCT. Defibrotide can effectively increase the survival rate of VOD patients.

Graft vs Host Disease ; Haploidy ; Hematopoietic Stem Cell Transplantation ; Heparin ; Hepatic Veno-Occlusive Disease ; Humans ; Incidence ; Polydeoxyribonucleotides ; Retrospective Studies ; Risk Factors

PURPOSE: Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. MATERIALS AND METHODS: Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. RESULTS: Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. CONCLUSION: Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.
Colorectal Neoplasms* ; Disease-Free Survival ; DNA ; Drug Therapy ; Fluorouracil ; Hepatic Veno-Occlusive Disease ; Humans ; Leucovorin ; Platelet Count ; Polymorphism, Genetic* ; Spleen ; Splenomegaly* ; Thrombocytopenia ; Treatment Outcome*

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.
Child* ; Cyclophosphamide* ; Drug Therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Hepatic Veno-Occlusive Disease* ; Humans ; Liver ; Rhabdomyosarcoma* ; Vincristine*