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Introduction: Hemophagocytic lymphohistiocytosis characterized by hemophagocytosis leading to uncontrolled inflammation; the most common etiology in secondary cases of hemophagocytic lymphohistiocytosis is viral infections, especially Epstein–Barr virus. Visceral leishmaniasis is a vectorborne protozoal disease caused by Leishmania donovani complex. It is common in tropical and subtropical regions, with 50,000–90,000 new cases annually. Case presentation: A 15-month-old Arab female was admitted to our hospital with 15 days of fever and decreased weight. On clinical examination, she had a markedly enlarged liver and spleen that were palpable 4 cm and 6 cm below the costal margin, respectively. The peripheral blood smear showed hypochromic microcytic anemia, poikilocytosis, reactive lymphocytosis, and mild thrombocytopenia. Bone marrow aspiration did not show malignancy or any other pathological findings. The patient was put on antibiotic therapy without improvement. Repeated bone marrow aspiration showed erythrophagocytosis; intracellular small round organisms looked like the amastigote form of Leishmania (Donovan bodies) with no evidence of malignancies. Her lab values showed ferritin greater than 500 ug/L, pancytopenia, and hypertriglyceridemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis. Conclusion: Hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis is an extensively rare phenomenon in the medical literature that causes challenges in diagnosis and management. Steroids should be used wisely to not cover the symptoms of infections or malignancy, and amphotericin B resistance should be kept in mind in unresponsive Leishmania cases. [ABSTRACT FROM AUTHOR]

Ascites is a pathological collection of free fluid in the peritoneal cavity, which is a common complication in patients with cirrhosis, an advanced liver disease. Bacterial infection increases the mortality rate of hospitalized patients with cirrhosis, irrespective of the severity of the liver disease. Around 60% of patients with compensated cirrhosis developed ascites within 10 years during the course of their disease. The in-hospital mortality rate due to spontaneous bacterial peritonitis (SBP) could exceed 90%, but with early diagnosis and prompt antibiotic therapy, this rate has been shown to decrease to 20%. Here, we enrolled adult (age ≥ 18) patients with liver disease with evidence of cirrhosis who developed ascites and assessed the presence of spontaneous ascites fluid infection (SAFI) in these patients. Of the total 218 patients, 22.9% (50/218) develop ascites infection. The liver organ function tests like alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin were found to be significantly (P < 0.05) higher in patients with ascites fluid infection compared to patients with non-ascites fluid infection. Of the gram-negative bacteria, K. pneumonia and E. coli were isolated and found to be 100% resistant to amoxicillin and clavulanate. From the gram-positive bacterial isolates, S. aureus was only resistant to penicillin, whereas Str. viridans was resistant to ceftriaxone, cefotaxime, cefepime, and penicillin. On the other hand, clinical features such as a history of jaundice, low arterial blood pressure, and ultrasound results such as a shrunken liver and enlarged spleen were also independent predictors of spontaneous bacterial peritonitis. In conclusion, given the high probability of death following SAFI, early detection, and treatment, as well as knowledge of the microbial agent, resistance profile, and predictive markers in various contexts, are essential for the timely diagnosis and management of SAFI in these patients. [ABSTRACT FROM AUTHOR]

Background: Our study aimed to analyze the characteristics of ultrasound images corresponding to each histological stage of primary biliary cholangitis (PBC). Methods: We prospectively analyzed 75 confirmed cases of PBC and used liver biopsy as the gold standard to determine the disease stage. Results: The typical ultrasound images of patients with PBC were characterized by a thickening of the portal vein wall (PVW) and periportal hypoechoic band (PHB) width with increasing histological stages, and significant increases in the left hepatic lobe diameter (LHLD) in stage II (by 64.0%) and stage III (by 69.2%). PHB width (r = 0.857, p < 0.001), PVW thickness (r = 0.488, p < 0.001), and spleen area (r = 0.8774, p < 0.001) were positively correlated with the histological stage. Significant changes were noted in the liver surface, echo texture, and edge between different stages. The areas under the receiver operating characteristic curve of composite indicators were 0.965 for predicting progressive PBC(≥ stage 2), and 0.926 for predicting advanced PBC(≥ stage 3). Conclusions: The ultrasound imaging characteristics of patients with PBC varied according to the histological staging. LHLD, PVW thickness, and PHB width were significantly correlated with the histological stage. A combination of high- and low-frequency ultrasound imaging can provide relevant cues regarding the degree of PBC progression and important clinical reference values. The application of all the ultrasound image findings as the composite indicators can better predict progressive and advanced PBC, providing important clinical reference values. [ABSTRACT FROM AUTHOR]

Background: Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM). Methods: The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques. Results: 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P < 0.05). Moreover, the median length of sample for TJLBs and PLBs were 10.0 and 16.5 mm (P < 0.05). The diagnostic efficiency of hepatopathy of unknown etiology of TJLB versus PLB groups before and after matching were 96.4% vs. 94.1% and 95.7% vs. 93.2%, respectively (P > 0.05). Conclusion: TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality. [ABSTRACT FROM AUTHOR]

Background: Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia is characterized by constitutive activation of Carbohydrate Response Element Binding Protein (ChREBP), a glucose-sensitive transcription factor. Previously, we showed that ChREBP activation limits non-alcoholic fatty liver disease (NAFLD) in hepatic GSD Ia. As ChREBP has been proposed as a pro-oncogenic molecular switch that supports tumour progression, we hypothesized that ChREBP normalization protects against liver disease progression in hepatic GSD Ia. Methods: Hepatocyte-specific G6pc knockout (L-G6pc−/−) mice were treated with AAV-shChREBP to normalize hepatic ChREBP activity. Results: Hepatic ChREBP normalization in GSD Ia mice induced dysplastic liver growth, massively increased hepatocyte size, and was associated with increased hepatic inflammation. Furthermore, nuclear levels of the oncoprotein Yes Associated Protein (YAP) were increased and its transcriptional targets were induced in ChREBP-normalized GSD Ia mice. Hepatic ChREBP normalization furthermore induced DNA damage and mitotic activity in GSD Ia mice, while gene signatures of chromosomal instability, the cytosolic DNA-sensing cGAS-STING pathway, senescence, and hepatocyte dedifferentiation emerged. Conclusions: In conclusion, our findings indicate that ChREBP activity limits hepatomegaly while decelerating liver disease progression and protecting against chromosomal instability in hepatic GSD Ia. These results disqualify ChREBP as a therapeutic target for treatment of liver disease in GSD Ia. In addition, they underline the importance of establishing the context-specific roles of hepatic ChREBP to define its therapeutic potential to prevent or treat advanced liver disease. [ABSTRACT FROM AUTHOR]

Background: Gaucher is an autosomal recessive inherited lysosomal storage disorder. The incidence of this disease is rare with a global estimate of around 1 in 57,000 to 1 in 75,000. Gaucher's disease is caused by a mutation in the glucocerebrosidase gene. Common symptoms of this disease include hepatosplenomegaly, moderate neurological symptoms, and late‑onset skeletal alterations. However, Gaucher can sometimes have rare presentations that lead to a delayed diagnosis in patients. This report discusses two adult cases of Gaucher's disease (type 1) with the same mutation but with unusual symptoms., Case Presentation: One patient was a 44-year-old man who had been experiencing chronic cough since he was 10 years old, and the other patient was a 27-year-old woman with itching, both atypical symptoms of Gaucher. Bronchodilators and prednisolone were administered for chronic cough and antihistamines and prednisolone were given for the itching, but little to no improvement was seen. Sonography tests revealed that both cases had splenomegaly, hepatomegaly, and liver malfunction, characteristic of Gaucher's disease. Bone marrow aspiration tests confirmed the presence of Gaucher's cells in their bones. The level of glucocerebrosidase enzyme in both cases was less than 1.5 nmol/mL/hour. Whole exon sequencing confirmed a mutation on exon 8 of the GBA1 gene in a homozygous form in both cases, resulting in a transversion mutation (C > G) at position c.798, leading to the substitution of phenylalanine 266 with leucine. Both patients were of Bakhtiyari ethnicity and had parents who were in a consanguineous marriage. After receiving Cerezyme treatment, both cases experienced a disappearance of their cough and itching symptoms., Conclusion: This report highlights the importance of recognizing the unusual presentation of Gaucher's disease especially in regions with high rates of consanguineous marriage and thalassemia. This knowledge can aid physicians in making accurate diagnoses and providing appropriate treatment., Competing Interests: Declarations. Ethics approval and consent to participate: Consent was gained by all applicants in this study. Consent for publication: Written informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: None declared., (© 2024. The Author(s).)

Background: We describe a case of Mauriac syndrome, which is a rare complication of poorly controlled type I diabetes that combines glycogenosis, hepatomegaly, growth retardation with a Cushingoid appearance that is most often present in children but also in young adults. Here we also describe another finding with this syndrome, which is hyperlactatemia.Case Presentation: The case is of a 16-year-old female of North African ethnicity with history of poorly controlled type I diabetes who was brought to the emergency department for dyspnea and tachycardia, treated initially for diabetic ketoacidosis. Her persistent hyperlactatemia helped to reveal a more subtle condition known as Mauriac syndrome after multiple examinations and follow-up.Conclusions: This case reports shows that Mauriac syndrome is a rare condition that should be considered in a setting of poorly controlled type I diabetes, hepatomegaly, Cushingoid appearance, and hyperlactatemia. The current treatment of this condition is a strict control of blood glucose levels with an attempt to achieve an acceptable glycated hemoglobin value. [ABSTRACT FROM AUTHOR]

Background: Pathogenic mutations in the PHKG2 are associated with a very rare disease-glycogen storage disease IXc (GSD-IXc)-and are characterized by severe liver disease.Case Presentation: Here, we report a patient with jaundice, hypoglycaemia, growth retardation, progressive increase in liver transaminase and prominent hepatomegaly from the neonatal period. Genetic testing revealed two novel, previously unreported PHKG2 mutations (F233S and R320DfsX5). Functional experiments indicated that both F223S and R320DfsX5 lead to a decrease in key phosphorylase b kinase enzyme activity. With raw cornstarch therapy, hypoglycaemia and lactic acidosis were ameliorated and serum aminotransferases decreased.Conclusion: These findings expand the gene spectrum and contribute to the interpretation of clinical presentations of these two novel PHKG2 mutations. [ABSTRACT FROM AUTHOR]

Background: Extragonadal choriocarcinoma is rare and can be associated with hyperthyroidism when producing very high levels of human chorionic gonadotropin.Case Presentation: A 62-year-old Hispanic female presented with a 3-week history of shortness of breath, palpitations, extreme weakness, new-onset hot flashes, and right flank pain. Her physical examination was remarkable for tachycardia, hepatomegaly, hyperreflexia, and tremor; goiter was absent. Laboratory studies revealed increased lactate dehydrogenase, alkaline phosphatase, suppressed thyroid stimulating hormone, very elevated T4, and absent thyroid stimulating immunoglobulin. 18F-fluorodeoxyglucose positron emission tomography-computed tomography exhibited hepatomegaly with multiple large fluorodeoxyglucose-avid liver masses and a focus of fluorodeoxyglucose avidity in the stomach with no structural correlate. A thyroid scan (99mTcO 4- ) showed diffusely increased tracer uptake. She was started on propranolol and methimazole. Upon stabilization of severe thyrotoxicosis, upper endoscopy was performed, showing a ~ 5 cm bleeding lesion in the greater stomach curvature body; biopsy was consistent with choriocarcinoma; beta-human chorionic gonadotropin hormone was 2,408,171 mIU/mL. The patient received methotrexate followed by etoposide and cisplatin. Methimazole was titrated down, and upon liver failure the medication was stopped. The thyrotoxicosis was effectively controlled with antithyroid drug and concurrent chemotherapy. At ~ 1.5 months after initial diagnosis, the patient died due to bleeding/acute liver failure with coagulation defects followed by multiple organ failure.Conclusions: Severe thyrotoxicosis can represent an unusual initial presentation of metastatic choriocarcinoma in the setting of extreme elevation of beta-human chorionic gonadotropin. Primary gastric choriocarcinoma is an aggressive malignancy with very poor outcomes. The co-occurrence of severe thyrotoxicosis with advanced primary gastric choriocarcinoma and imminent liver failure complicates management options. [ABSTRACT FROM AUTHOR]

Background: Alcoholism is a well-known risk factor for liver injury and is one of the major causes of hepatic steatosis worldwide. Although many drugs have been reported to have protective effects against acute alcohol-induced hepatotoxicity, there is limited available treatment for alcoholic liver disease (ALD), indicating an urgent need for effective therapeutic options. Herein, we first reported the protective effects of magnesium isoglycyrrhizinate (MgIG) on acute alcohol-induced hepatic steatosis and its related mechanisms in a zebrafish model. Methods: Alcohol was administered directly to embryo medium at 5 days post-fertilization (dpf) for up to 32 h. MgIG was given to the larvae 2 h before the administration of alcohol and then cotreated with alcohol starting at 5 dpf. Oil red O staining was used to determine the incidence of steatosis, and pathological features of the liver were assessed by hematoxylin–eosin staining. Biological indexes, total cholesterol (TC) and triacylglycerol (TG) were detected in the livers of zebrafish larvae. Morphological changes in the livers of zebrafish larvae were observed using liver-specific EGFP transgenic zebrafish (Tg(lfabp10a:eGFP)). The expression levels of critical molecules related to endoplasmic reticulum (ER) stress and lipid metabolism were detected by qRT–PCR, whole-mount in situ hybridization and western blotting. Results: Alcohol-treated larvae developed hepatomegaly and steatosis after 32 h of exposure. We found that MgIG improved hepatomegaly and reduced the incidence of steatosis in a dose-dependent manner by oil red O staining and diminished deposits of alcohol-induced fat droplets by histologic analysis. Moreover, MgIG significantly decreased the levels of TC and TG in the livers of zebrafish larvae. Furthermore, the expression levels of critical genes involved in ER stress (atf6, irela, bip, chop) and the key enzymes regulating lipid metabolism (acc1, fasn, hmgcs1 and hmgcra) were significantly higher in the alcohol-treated group than in the control group. However, in the MgIG plus alcohol-treated group, the expression of these genes was markedly decreased compared with that in the alcohol-treated group. Whole-mount in situ hybridization and western blotting also showed that MgIG had an effect on the expression levels of critical genes and proteins involved in lipid metabolism and ER stress. Our results revealed that MgIG could markedly regulate these genes and protect the liver from ER stress and lipid metabolism disorders. Conclusions: Our study is the first to demonstrate that MgIG could protect the liver from acute alcohol stimulation by ameliorating the disorder of lipid metabolism and regulating ER stress in zebrafish larvae. [ABSTRACT FROM AUTHOR]

Background: Pyruvate kinase deficiency is an exceptionally rare autosomal recessive Mendelian disorder caused by bi-allelic pathogenic variants in the PKLR gene. It is mainly characterized by chronic nonspherocytic hemolytic anemia though other symptoms such as splenomegaly, hepatomegaly, pallor, fatigue, iron overload, shortness of breath, hyperbilirubinemia, and gallstones might also prevail.Case Presentation: We present here a novel genetic defect in the PKLR gene that correlates with pyruvate kinase deficiency phenotype in a consanguineous family from North-Western Pakistan. The family included three affected individuals who were all born to consanguineous parents. The proband, a 13-year-old female of Pashtun ethnicity, showed chronic nonautoimmune hemolytic anemia since birth, extremely low hemoglobin (7.6 g/dL) and pyruvate kinase (12.4 U/g Hb) levels, splenomegaly, and hepatomegaly. Bone marrow aspirate showed a markedly decreased myeloid to erythroid ratio and hypercellular marrow particles due to hyperplasia of the erythroid elements. Molecular characterization of the proband's genomic DNA uncovered a likely pathogenic homozygous missense variant p.[D339N] in exon 7 of the PKLR gene. In-depth in silico analysis and familial cosegregation implies p.[D339N] as the likely cause of pyruvate kinase deficiency in this family. Further in vitro or in vivo studies are required to validate the impact of p.[D339N] on protein structure and/or stability, and to determine its role in the disease pathophysiology.Conclusions: In summary, these findings suggest a novel genetic defect in the PKLR gene as a likely cause of pyruvate kinase deficiency, thus further expanding the mutational landscape of this rare Mendelian disorder. [ABSTRACT FROM AUTHOR]

Background: Subgroup J avian leukosis virus (ALV-J) is an oncovirus which can induce multiple types of tumors in chicken. In this report, we found novel ALV-J infection is closely associated with serious hepatomegaly and splenomegaly in chicken. Case presentation: The layer chickens from six flocks in Jiangsu province, China, showed serious hemoperitoneum, hepatomegaly and splenomegaly. Histopathological results indicated focal lymphocytic infiltration, cell edema and congestion in the liver, atrophy and depletion of lymphocyte in the spleen. Tumor cells were not detected in all the organs. avian hepatitis E virus (aHEV), which is thought to be the cause of a very similar disease, big liver and spleen disease (BLS), was not detected. Other viruses causing tumors or liver damage including Marek's disease virus (MDV), reticuloendotheliosis virus (REV), fowl adenovirus (FAdV) and chicken infectious anemia virus (CIAV) were also proved negative by either PCR or RT-PCR. However, we did detect ALV-J in those chickens using PCR. Only novel ALV-J strains were efficiently isolated from these chicken livers. Conclusions: This is the first report that chicken hepatomegaly and splenomegaly disease was closely associated with novel ALV-J, highlighting the importance of ALV-J eradication program in China. [ABSTRACT FROM AUTHOR]

Background: The Mauriac syndrome was described in 1930 as a peculiar combination of poorly controlled diabetes mellitus type 1, stunted growth and glycogenic hepatopathy. More recently, lactic acidosis was recognized as an additional feature, often induced by insulin treatment. Case presentation: A 17-year old girl known for diabetes type 1A and Mauriac syndrome was admitted to the emergency room with hyperglycemia of > 41 mmol/l without ketoacidosis. Under a standard insulin regimen, hyperglycemia was rapidly corrected but marked hyperlactatemia occurred. Conclusions: The mechanism of impaired glucose utilization and lactate elevation independent of ketoacidosis in Mauriac syndrome is intriguing. The rarity of Mauriac syndrome and its resemblance to glycogen storage diseases suggest the presence of a specific metabolic or genetic predisposition that remains to be identified. [ABSTRACT FROM AUTHOR]

Background: Tetratrichomonas gallinarum is parasitic protozoa with a wide host range. However, its lethal infection is rare reported. Case presentation: Here, we described the first lethal cases of T. gallinarum infection in black swans in China. Five black swans died within a week in succession without obvious symptoms except mild diarrhea. At necropsy, severe lesions were observed in caeca with thickened caecal walls and hemorrhages in the mucosa. A large number of moving trophozoites were found in the contents of the cecum by microscopic examination. The livers were enlarged with multiple bleeding spots on the surface. Histopathology of the livers showed mononuclear cell infiltration and moderate hyperplasia of fibrous tissue. The histopathology of the cecum showed that the villi of the cecum were edematous. Finally, the presence of T. gallinarum was determined by specific PCR andin-situ hybridization assay. Additionally, common pathogens that can cause similar symptoms were excluded. Conclusions: The death of the black swan was caused by T. gallinarum, suggesting that the parasite might be a new threat to the Cygnus birds. [ABSTRACT FROM AUTHOR]

Background: Glycogen storage disease (GSD) type IXb is one of the rare variants of GSDs. It is a genetically heterogeneous metabolic disorder due to deficient hepatic phosphorylase kinase activity. Diagnosis of GSD can be difficult because of overlapping manifestations. Mutation analysis of the genes related to each type of GSD is supposed to be problem-solving, however, the presence of novel mutations can be confusing. In this case report, we will describe our experience with a young girl with the diagnosis of GSD and two novel mutations related to GSD type IXb.Case Presentation: A 3-year- old girl presented with short stature, hepatomegaly, and liver cirrhosis. No specific diagnosis was made based on laboratory data, so liver biopsy and targeted-gene sequencing (TGS) were performed to find out the specific molecular basis of her disease. It was confirmed that the patient carries two novel variants in the PHKB gene. The variant in the PHKB gene was classified as pathogenic.Conclusions: This is the first reported case of a dual molecular mutation of glycogen storage disease type IXb in the same patient. Two novel variants in PHKB were identified and one of them was a pathogenic split-site mutation. In conclusion, for the first time, identification of the novel variants in this patient expands the molecular and the phenotype basis of dual variants in GSD-IXb. [ABSTRACT FROM AUTHOR]

Background: Childhood hypoglycemia in combination with hepatomegaly is suspicious for inborn errors of metabolism. Cystic fibrosis typically presents with failure to thrive, pulmonary and gastrointestinal symptoms. Hepatic involvement and hypoglycemia can occur in a significant number of patients, although hepatomegaly is uncommon.Case Presentation: A 28 months old boy was presented with recurrent upper airways infections, progressive lethargy and weight loss. Clinically hepatomegaly was the main presenting feature and hypoglycemia (minimum 1.4 mmol/l) was noted as were elevated transaminases. The patient did not produce enough sweat to analyze it. Infectious causes for hepatitis were excluded and a broad metabolic work-up initiated. A therapy with starch was initiated to control hypoglycemia. In further course loose stools were reported and pancreatic elastase was found to be reduced. A further sweat test yielded pathological chloride concentration and genetic testing confirmed the diagnosis of cystic fibrosis.Conclusions: Cystic fibrosis is a systemic disease and less common presentations need to be considered. Even in the age of CF-newborn screening in many countries CF needs to be ruled out in typical and atypical clinical presentations and diagnostics need to be repeated if inconclusive. [ABSTRACT FROM AUTHOR]

Background: Severe hepatosplenic complications arise in patients with chronic Schistosoma mansoni infection after heavy exposure to disease agents in endemic areas. These complications are rarely reported and, hence, underestimated. Case presentation: We report on eight patients with severe morbidity associated with S. mansoni infection in Ituri Province, northeastern Democratic Republic of Congo (DRC). The patients were identified during a community-based survey in 2017; one patient was seen at the district hospital. After taking the patients' history, a clinical examination and an abdominal ultrasonographical examination were performed. S. mansoni infection was diagnosed in fecal (Kato-Katz technique) and urine (point-of-case circulating cathodic antigen test) samples. These eight patients with severe intestinal and hepatosplenic complications were identified from four villages with high S. mansoni infection prevalence and related morbidity. The patients' ages ranged from 19 to 57 years; four patients were women. Three patients reported hematemesis. Two patients were severely anemic. All patients reported non-specific abdominal symptoms, such as diarrhea (six patients), abdominal pain (seven patients), and blood in the stool (five patients), as well as weight loss (two patients). Abdominal ultrasonography revealed ascites in four patients. All patients had portal hypertension with hepatomegaly (seven patients) or splenomegaly (five patients). Of the six patients with a discernable liver parenchyma pattern, five displayed pattern F and three patient displayed pattern E. Liver parenchyma was not visible for two patients with severe ascites. An S. mansoni infection was confirmed in six patients, with infection intensity ranging from light to heavy. All S. mansoni positive patients were treated with praziquantel (40 mg/kg body weight) and referred to the district hospital for follow-up. One patient with severe ascites died two weeks after we saw her. Due to security and accessibility reasons, the villages could not be visited again and the patients were lost to follow-up. Conclusions: Our observations of patients with severe schistosomiasis document the severe degree of endemicity of S. mansoni in the province and suggest an urgent need for adequate schistosomiasis control measures that target vulnerable population groups and address severe complications. [ABSTRACT FROM AUTHOR]

Background: The liver is one of the most frequent sites of metastases in rectal cancer. This study aimed to evaluate how the development of synchronous or metachronous liver metastasis and overall survival are impacted by baseline liver steatosis and chemotherapy-induced liver damage in rectal cancer patients.Methods: Patients diagnosed with stage II to IV rectal cancer between 2010 and 2016 in our province with suitable baseline CT scan were included. Data on cancer diagnosis, staging, therapy, outcomes and liver function were collected. CT scans were retrospectively reviewed to assess baseline steatosis (liver density < 48 HU and/or liver-to-spleen ratio < 1.1). Among patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was defined as steatosis appearance, ≥ 10% liver volume increase, or significant increase in liver function tests.Results: We included 283 stage II to IV rectal cancer patients with suitable CT scan (41% females; mean age 68 ± 14 years). Steatosis was present at baseline in 90 (31.8%) patients, synchronous liver metastasis in 42 (15%) patients and metachronous liver metastasis in 26 (11%); 152 (54%) deaths were registered. The prevalence of synchronous liver metastasis was higher in patients with steatosis (19% vs 13%), while the incidence of metachronous liver metastasis was similar. After correcting for age, sex, stage, and year of diagnosis, steatosis was not associated with metachronous liver metastasis nor with overall survival. In a small analysis of 63 patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was associated with higher incidence of metachronous liver metastasis and worse survival, results which need to be confirmed by larger studies.Conclusions: Our data suggest that rectal cancer patients with steatosis had a similar occurrence of metastases during follow-up, even if the burden of liver metastases at diagnosis was slightly higher, compatible with chance. [ABSTRACT FROM AUTHOR]

Background: Amiodarone is an antiarrhythmic drug that has been recognized to induce hepatotoxicity. We report a case of acute-on-chronic liver failure (ACLF) in a patient who was receiving amiodarone for more than 2 years. The patient developed cirrhosis and suppurative microabscesses of the liver and died of progressive liver failure.Case Presentation: A 69-year-old woman with risk factors for nonalcoholic fatty liver disease (NAFLD) was treated with oral amiodarone at a daily dose of 400 mg for more than 2 years, until she developed epigastralgia and vomiting. Initial laboratory findings included leukocytosis and elevated liver enzymes. Images of abdominal computed tomography scan revealed diffusely increased hepatic attenuation density (in contrast to decreased density in NAFLD), hepatomegaly, periportal edema, and ascites. Liver biopsy targeting the hotspot identified through positron emission tomography confirmed the diagnosis of amiodarone-associated chronic steatohepatitis and superimposed microabscesses. The patient died of progressive ACLF despite intensive supportive care.Conclusion: Accumulation of amiodarone can result in chronic liver disease and pose an additional risk of ACLF following infection. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1–3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects' clinical manifestations and laboratory tests were analyzed retrospectively. Results: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 μg/L, the sensitivity and specificity of D-Dimer was 88.90 and 90.20%, respectively. Conclusion: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV. [ABSTRACT FROM AUTHOR]

Background: Hydroa Vacciniforme-like Lymphoproliferative Disorder (HV-LPD) is the name given to a group of Epstein-Barr virus (EBV)-associated diseases. It resembles hydroa vacciniforme (HV), the rarest form of photosensitivity, and is a T-cell disorder associated with an Epstein-Barr virus infection. The majority of diagnosed cases occur in East Asia and South America. It is rare in the United States and Europe. Multiple studies have revealed the clinical manifestation of an enlarged liver, but no gold standard such as pathology has yet supported this as a clinical sign of HV-LPD.Case Presentation: Here, we report a case of a 34-year-old Asian female with definite liver invasion. The patient had complained of a recurring facial rash for many years. The patient was admitted to the hospital because of an enlarged liver. After hospitalization, she was given an EB virus nucleic acid test. The EB virus nucleic acid test was positive, and pathological examination suggested that HV-LPD had invaded the skin, bone marrow, and liver. After being given antiviral treatment, the patient's symptoms were mitigated.Conclusions: Our case confirms the liver damage was caused by HV-LPD and the effectiveness of antiviral treatment. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy that is strongly associated with chronic liver disease. Isolated hepatic tuberculosis is an uncommon type of tuberculosis. Concomitant occurrence of both conditions is extremely rare.Case Presentation: We report the case of a 47-year-old man who presented with fever and abdominal pain for 3 months prior to presentation. He reported a history of anorexia and significant weight loss. Abdominal examination revealed a tender, enlarged liver. Abdominal computed tomography (CT) demonstrated a solid heterogeneous hepatic mass with peripheral arterial enhancement, but no venous washout, conferring a radiological impression of suspected cholangiocarcinoma. However, a CT-guided biopsy of the lesion resulted in the diagnosis of concomitant HCC and isolated hepatic tuberculosis.Conclusion: A rapid increase in tumor size should draw attention to the possibility of a concomitant infectious process. Clinicians must have a high index of suspicion for tuberculosis, especially in patients from endemic areas, in order to initiate early and proper treatment. [ABSTRACT FROM AUTHOR]

Background: Cystinosis is a multisystemic disease resulting from cystine accumulation primarily in kidney and many other tissues. We intended to study the evolution of less commonly seen extrarenal complications of cystinosis in a group of patients who have periods without cysteamine treatment.Methods: Gastrointestinal and muscular complications of cystinosis were studied in a group of 21 patients.Results: Twenty one patients were included in the study. Among them, 14 were homozygous and 3 were compound heterozygous for CTNS mutations. The median age of diagnosis was 15 months (range; 5 months-14 years) and the mean age at last visit was 11.3 ± 6.5 years. Nine patients (42%) had end stage renal disease at a mean age of 10.6 years (6.5-17 years). Abdominal ultrasonography and portal vein doppler ultrasonography were performed in19 patients, 14 of them (74%) had hepatomegaly, 10 patients (53%) had granular pattern or heterogeneity of liver. Only one patient had high transaminase levels and liver biopsy showed cystine crystals in the liver. Eleven patients (58%) had borderline or increased portal vein minimum and maximum flow velocities. One patient had CK level of 9024 U/L and electromyographic study showed active myopathic involvement. Two patients were found to have gastroesaphageal reflux only and 4 patients were found to have esophageal remnants in addition to reflux.Conclusions: In addition to renal functions, extrarenal organs may be affected from cystine accumulation even in childhood, especially in patients who are incompliant to treatment, resulting in complications such as swallowing difficulty, hepatomegaly and portal hypertension. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs): TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis.Case Presentation: A 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died.Conclusions: This is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections. [ABSTRACT FROM AUTHOR]

Background: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction., Methods: Clinical, biochemical, genetic, treatment, and follow-up data for 11 pediatric patients with FBS were retrospectively analysed., Results: Hepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO 3 ) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO - ) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO 3 - and AKP (p < 0.05). At the last follow-up, 5/7 patients with elevated AKP had nephrocalcinosis. The mean height standard deviation score (Ht SDS) of eight patients with regular treatment increased from - 4.1 to -3.5 (p = 0.02). Recombinant human growth hormone (rhGH) was administered to 4/9 patients, but their Ht SDS did not improve significantly (p = 0.13). Fourteen variants of the SLC2A2 gene were identified, with six being novel, among which one was recurrent: c.1217T > G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient., Conclusions: Early diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended in FBS patients who have normal GH stimulation tests. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families., (© 2024. The Author(s).)

Background: Compounds in clinical development for nonalcoholic steatohepatitis (NASH) improve liver histopathology in diet-induced obese mouse models of biopsy-confirmed NASH. Since the biopsy section used for histopathological evaluation represents only < 1% of the whole mouse liver, we evaluated how well biopsy-based quantitative image analyses correlate to stereology-based whole-liver quantitative changes upon drug treatment.Methods: Male leptin-deficient Lepob/Lepob mice were fed the Amylin liver NASH (AMLN) diet for 16 weeks before stratification into treatment groups using a biopsy-based evaluation of type I collagen αI (col1a1) levels. Mice were treated for 8 weeks with either vehicle (PO, QD), liraglutide (0.4 mg/kg, SC, QD), elafibranor (30 mg/kg, PO, QD) or INT-767 (10 mg/kg, PO, QD). Terminal quantitative histological assessment of liver lipid (hematoxylin-eosin staining), inflammation (galectin-3 immunohistochemistry (IHC); gal-3), and fibrosis (col1a1 IHC) was performed on terminal liver biopsies and compared with stereologically sampled serial sections spanning the medial, left and right lateral lobe of the liver.Results: The distribution of liver lipid and fibrosis was markedly consistent across lobes, whereas inflammation showed some variability. While INT-767 and liraglutide significantly reduced total liver weight by 20 and 48%, respectively, elafibranor tended to exacerbate hepatomegaly in Lepob/Lepob-NASH mice. All three compounds markedly reduced biopsy-based relative liver lipid content. Elafibranor and INT-767 significantly reduced biopsy-based relative gal-3 levels (P < 0.001), whereas INT-767 and liraglutide tended to reduce relative col1a1 levels. When changes in liver weight was accounted for, both INT-767 and liraglutide significantly reduced biopsy-based total col1a1 content. Although minor differences in absolute and relative liver lipid, inflammation and fibrosis levels were observed across lobes, the interpretation of drug-induced effects were consistent with biopsy-based conclusions. Notably, the incorporation of changes in total liver mass revealed that liraglutide's efficacy reached statistical significances for all analyzed parameters.Conclusions: In conclusion, in-depth analyses of liver homogeneity demonstrated that drug-induced improvement in liver biopsy-assessed histopathology is representative for overall liver effects assessed using stereology. Importantly, these findings reveal how changes in whole-liver mass should be considered to provide a deeper understanding of apparent drug treatment efficacy in preclinical NASH studies. [ABSTRACT FROM AUTHOR]

Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment of adult and paediatric patients with Type 1 Gaucher disease (GD) in several countries and the first plant cell-expressed recombinant therapeutic protein approved by the US Food and Drug Administration for humans. Here, we review the findings across six key taliglucerase alfa clinical studies. A total of 33 treatment-naïve adult patients were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 9-month, multicentre, randomized, double-blind, parallel-group, dose-comparison pivotal study, after which eligible patients continued into two consecutive extension studies; 17 treatment-naïve adult patients completed 5 total years of treatment with taliglucerase alfa. In the only ERT study focused on exclusively paediatric patients with GD, 11 treatment-naïve children were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 12-month, multicentre, double-blind study; nine completed 3 total years of treatment in a dedicated paediatric extension study. The effect of switching patients from imiglucerase to taliglucerase alfa was also investigated in a separate 9-month study that included 26 adults and five children; 10 adults completed a total of 3 years and two children completed a total of 2.75 years of taliglucerase alfa treatment in the extension studies. All studies evaluated safety and spleen volume, liver volume, platelet count, haemoglobin concentration, and biomarkers as measures of efficacy. Detailed results from baseline through the end of these studies are presented. Taliglucerase alfa was well tolerated, and adverse events were generally mild/moderate in severity and transient. Treatment with taliglucerase alfa resulted in improvements (treatment-naïve patients) or stability (patients switched from imiglucerase) in visceral, haematologic, and biomarker parameters. Together, this comprehensive data set supports the treatment of adult and paediatric patients with GD who are naïve to ERT or who have previously been treated with imiglucerase. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mansoni and Hepatitis C virus (HCV) are co-existence in sub-Saharan Africa and co-infection is common among humans population. The immunological responses characterized with Th2-immune responses for S. mansoni and Th1-immune responses for HCV are responsible for development hepatic morbidities in infected individuals. However, the co-occurrences of S. mansoni and HCV infection, their related ultrasound detectable morbidities and associated risk factors at community levels have not been examined in fishing communities, north-western Tanzania. In this context, the present study covers that gap.Methods: A cross-sectional study was conducted among 1924 asymptomatic individuals aged 15-55 years in four fishing villages (Igombe, Igalagala, Sangabuye and Kayenze) of Northwestern Tanzania. A single stool sample was collected from each study participants and examined for S. mansoni eggs using Kato Katz technique. Hepatitis C surface antigen (HCVsAg) was determined from a finger prick blood sample using a rapid test.Results: Overall, 51.8% (997/1924; 95%CI: 49.6-54.1) of the study participants were infected with S. mansoni and had a mean intensity of 223.7epg (95%; 202.4-247.1). Of the study participants, 90 (4.7%) were infected with hepatitis C virus (HCV). Overall, 2. 4% (47/1924) of the study participants were co-infected with S. mansoni and hepatitis C virus. Among the co-infected individuals, 42.6%, 70.2% and 19.1% had splenomegaly, hepatomegaly and periportal fibrosis (PPF). Factors associated with S. mansoni/HCV co-infection were being aged 26-35 years (aRR = 2.67, 95%CI: 1.03-6.93, P < 0.04), 46-55 years (aRR = 2.89, 95%CI: 1.10-7.57, P < 0.03) and having marked hepatomegaly (aRR = 2.32, 95%CI: 1.09-4.9, P < 0.03).Conclusion: In this setting, S. mansoni and Hepatitis C are co-endemic and a proportion of individuals were co-infected. Hepatosplenic morbidities characterized with hepatomegaly, splenomegaly, hepatosplenomegaly and PPF were observed in co-infected individuals. These results highlight the need for integrated interventions measures against parasitic and viral diseases. [ABSTRACT FROM AUTHOR]

Background: Disseminated cryptococcosis is a rare and fatal disease, and limited data exist regarding it in children. This study aimed to investigate the clinical characteristics of disseminated cryptococcosis in previously healthy children in China.Methods: Hospitalized patients with disseminated cryptococcosis were enrolled during January 1996 to December 2015 in Beijing Children's Hospital, Capital Medical University, China. Data on clinical manifestations, laboratory tests, treatment, and prognosis were evaluated.Results: A total of 52 pediatric patients with no underlying disease were enrolled, including 38 boys and 14 girls. Only 10 cases had a history of exposure to pigeon droppings. Fever, cough, and hepatomegaly were 3 main manifestations of disseminated cryptococcosis. However, headache was more common in patients with central nervous system (CNS) invasion than in patients with non-CNS invasion (P < 0.05). Lung (96.2%, 50/52) was the most commonly invaded organ, but only 9.6% (5/52) of patients had respiratory signs. The most common findings on chest imaging were hilar or mediastinal lymphadenopathy (46.8%, 22/47), and nodules (44.7%, 21/47), including small nodules in a scattered distribution (57.1%, 12/21) or miliary distribution (42.9%, 9/25), especially localized in subpleural area. Subsequent invasion occurred in the CNS, abdomen lymph nodes, liver, spleen, peripheral lymph nodes, and skin. In all patients, 42.3% (22/52) and 51.9% (27/52) had elevated eosinophils or IgE, respectively. The positive rate of serum cryptococcal antigen was higher, especially in patients with CNS invasion (approximately 83.3%), than with other primary methods used for pathogen detection, including cerebrospinal fluid (CSF) cryptococcal antigen, cultures of blood, bone marrow, or CSF, and CSF ink staining. The overall mortality rate of pediatric patients in our study was 11.5% (6/52). Some cases had long-term sequela, including hydrocephalus, cirrhosis, or blindness.Conclusions: Disseminated cryptococcosis can occur in previously healthy or immunocompetent children in China. Lung and CNS were most commonly invaded by this disease. Furthermore, most cases usually showed no obvious or specific symptoms or signs, and therefore pediatricians should pay more careful attention to identify this disease. [ABSTRACT FROM AUTHOR]

Background: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by deficiency in acid beta-glucosidase. GD exhibits a wide clinical spectrum of disease severity with an unpredictable natural course. Plasma chitotriosidase activity and CC chemokine ligand 18 (CCL18) have been exchangeably used for monitoring GD activity and response to enzyme replacement therapy in conjunction with clinical assessment. Yet, a large-scale head-to-head comparison of these two biomarkers is currently lacking. We propose a collaborative systematic review with meta-analysis of individual participant data (IPD) to compare the accuracy of plasma chitotriosidase activity and CCL18 in assessing type I (i.e., non-neuropathic) GD severity. Methods: Eligible studies include cross-sectional, cohort, and randomized controlled studies recording both plasma chitotriosidase activity and CCL18 level at baseline and/or at follow-up in consecutive children or adult patients with type I GD. Pre-specified surrogate outcomes reflecting GD activity include liver and spleen volume, hemoglobin concentration, platelet count, and symptomatic bone events with imaging confirmation. Primary studies will be identified by searching Medline (1995 onwards), EMBASE (1995 onwards), and Cochrane Central Register of Controlled Trials (CENTRAL). Electronic search will be complemented by contacting research groups in order to identify unpublished relevant studies. Where possible, IPD will be extracted from published articles. Corresponding authors will be invited to collaborate by supplying IPD. The methodological quality of retrieved studies will be appraised for each study outcome, using a checklist adapted from the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcome will be a composite of liver volume >1.25 multiple of normal (MN), spleen volume >5 MN, hemoglobin concentration <11 g/dL, or platelet count <100 x 10 9/L. Effect size estimates for biomarker comparative accuracy in predicting outcomes will be reported as differences in areas under receiver operating characteristic curves along with 95% confidence intervals. Effect size estimates will be reported as (weighted) mean differences along with 95% confidence intervals for each biomarker according to outcomes. IPD meta-analysis will be conducted with both one- and two-stage approaches. Discussion: Valid and precise accuracy estimates will be derived for CCL18 relative to plasma chitotriosidase activity in discriminating patients according to GD severity. Systematic review registration: PROSPERO 2015 CRD42015027243 [ABSTRACT FROM AUTHOR]

Background: Solitary fibrous tumours (SFT) are neoplasms of mesenchymal origin that predominantly arise from the pleura. SFT of the liver (SFTL) are a rare occurrence with little number of cases reported in English literature. Malignant cases of hepatic SFT are an even rarer occurrence. For this reason, the prognostic evaluation of SFTLs is unknown and difficult to measure. Methods: A search on English literature on "Solitary Fibrous Tumour of the Liver" was conducted on common search engines (PubMed, Google). All published articles, case reports and literature reviews and their reference lists were reviewed. Case report: This paper presents a 61-year-old male who was referred to a tertiary hospital in April 2010 with marked hepatomegaly. USS, CT and MRI scans were suggestive of a neoplasm, and the patient underwent a subsegmental IVb resection in June 2010. The specimen demonstrated histological and immunohistochemical features of malignant SFTL with clear resection margins. The patient was followed up regularly for 3 years with imaging and no suggestion of recurrence. Six years after the initial surgery, the patient represented with worsening right upper quadrant pain and dyspnoea secondary to extensive tumour recurrence adjacent to the resection site and metastatic deposits in the pleura. The patient was managed symptomatically and discharged for community follow-up after palliative involvement. Conclusions: SFTL are rare with only 84 cases reported in the English Literature including the present case. The average age of patients is 57.1 and occurs in females more than males (1.4:1). Most SFTLs follow a benign course, however, 17.9% of cases displayed malignant histological features. Only three cases including the current case are reported to have both local recurrence and metastasis. Surgical resection remains the mainstay of treatment and appears to be curative of most cases. The rarity of this tumour makes it difficult to evaluate its prognosis and natural course. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. Methods: Male ICR mice were given a single oral dose of Sch B (0.25-2 g/kg). Sch B-induced changes in serum levels of biomarkers, such as TG, total cholesterol (TC), apolipoprotein B48 (ApoB 48), very-low-density lipoprotein (VLDL), non-esterified fatty acid (NEFA) and hepatic growth factor (HGF), as well as hepatic lipids and mass, epididymal adipose tissue (EAT) and adipocyte size, and histological changes of the liver and EAT were examined over a period of 12-120 h after Sch B treatment. Results: Serum and hepatic TG levels were increased by 1.0-4.3 fold and 40-158% at 12-72 h and 12-96 h, respectively, after Sch B administration. Sch B treatment elevated serum ApoB 48 level (up to 12%), a marker of exogenous TG, but not VLDL, as compared with the vehicle treatment. Treatment with Sch B caused a time-/dose-dependent reduction in EAT index (up to 39%) and adipocyte size (up to 67%) and elevation in serum NEFA level (up to 55%). Sch B treatment induced hepatic steatosis in a time-/dose-dependent manner, as indicated by increases in total vacuole area (up to 3.2 fold vs. the vehicle control) and lipid positive staining area (up to 17.5 × 103 μm2) in liver tissue. Hepatic index and serum HGF levels were increased by 18-60% and 42-71% at 12-120 h and 24-72 h post-Sch B dosing, respectively. In addition, ultrastructural changes, such as increase in size and disruption of cristae, in hepatic mitochondria were observed in Sch B-treated mice. Conclusion: Our findings suggest that exogenous sources of TG and the breakdown of fat storage in the body contribute to Sch B-induced hypertriglyceridemia and hepatic steatosis in mice. Hepatomegaly (a probable hepatotoxic action) caused by Sch B may result from the fat accumulation and mitochondrial damage in liver tissue. [ABSTRACT FROM AUTHOR]

Background: This report presents a case of a 57- year old female with advanced Hepatic Alveolar Echinococcosis causing a secondary Budd-Chiari Syndrome due to infiltration of the suprahepatic inferior vena cava treated successfully by liver transplantation.Case Presentation: A temporary veno-venous bypass was introduced, but a typical end to end cavo-caval anastomosis wasn't possible in this case. In order to access a disease free part of the inferior vena cava, an oval window of the diaphragm was excised, providing communication between the peritoneum and pericardium. A vascular clamp was placed onto the right atrium which allowed for an atrial-caval anastomosis. The remainder of hepatectomy was performed in a conventional manner. In the post-operative period and during the 18 month follow-up there were no complications. The patient remains in good general condition with optimal graft function.Conclusions: A hepato-atrial anastomosis with a pericardial-peritoneum window during liver transplantation is feasible and extends the curability potential for patients with advanced Hepatic Alveolar Echinococcosis considered for liver transplantation. [ABSTRACT FROM AUTHOR]

Background: High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant., Methods: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m 2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank., Discussion: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice., Trial Registration: Netherlands Trial Register NL8902 , registered on 2020-09-15., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To determine the clinical and laboratory differences between leukemic arthritis (LA) and juvenile idiopathic arthritis (JIA) at the onset of the disease., Material and Methods: Patients under 16 years of age, both genders, who presented for the first time to the pediatric rheumatology service with a diagnosis of probable JIA, with arthritis and without peripheral blood blasts, in which the final diagnosis was acute lymphoblastic leukemia (ALL) or JIA. The clinical and laboratory characteristics of the patients were compared, chi-square and relative risk were used for categorical variables, and the Mann-Whitney U and T-test for the comparison of means between groups. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA., Results: A total of 76 patients, 14 with LA and 62 with JIA, were analyzed. The mean age at diagnosis was lower in the leukemic arthritis group, the female gender prevailed in the JIA group, and the time to onset of symptoms was lower in the leukemic arthritis group. Patients with leukemic arthritis showed increased pain intensity, fever, weight loss, nocturnal diaphoresis, lymph node enlargement, hepatosplenomegaly, and pain that did not improve with analgesic administration. Laboratory parameters with statistical significance were the presence of anemia, leukopenia, and neutropenia. The platelet count was significant but in a low normal value, compared to the JIA. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA. The probability associated with the statistic (Chi-square) was 0.000, and the Cox and Snell R2 and Nagelkerke R2 values were 0.615 and 1, respectively. The developed model correctly classified 100% of the cases., Conclusions: The diagnosis of acute lymphoblastic leukemia should be ruled out in patients who present with arthritis and hematological alterations, mainly leukopenia and neutropenia, with joint pain disproportionate to the degree of arthritis, predominantly at night and that does not improve with the use of analgesics, fever, lymph nodes, and hepatosplenomegaly. Criteria are suggested to differentiate both diseases., (© 2023. The Author(s).)

Background: From 2014 to 2015 in China, many broiler breeder and layer hen flocks exhibited a decrease in egg production and some chickens developed hepatitis syndrome including hepatomegaly, hepatic necrosis and hemorrhage. Avian hepatitis E virus (HEV) and avian leucosis virus subgroup J (ALV-J) both cause decreasing in egg production, hepatomegaly and hepatic hemorrhage in broiler breeder and layer hens. In the study, the seroprevalence of avian HEV and ALV-J in these flocks emerging the disease from Shandong and Shaanxi provinces were investigated. Results: A total of 1995 serum samples were collected from 14 flocks with hepatitis syndrome in Shandong and Shaanxi provinces, China. Antibodies against avian HEV and ALV-J in these serum samples were detected using iELISAs. The seroprevalence of anti-avian HEV antibodies (35.09%) was significantly higher than that of anti-ALV-J antibodies (2.16%) (p = 0.00). Moreover, the 43 serum samples positive for anti-ALV-J antibodies were all also positive for anti-avian HEV antibodies. In a comparison of both provinces, Shandong chickens exhibited a significantly higher seroprevalence of anti-avian HEV antibodies (42.16%) than Shaanxi chickens (26%) (p = 0.00). In addition, the detection of avian HEV RNA and ALV-J cDNA in the liver samples from the flocks of two provinces also showed the same results of the seroprevalence. Conclusions: In the present study, the results showed that avian HEV infection is widely prevalent and ALV-J infection is endemic in the flocks with hepatitis syndrome from Shandong and Shaanxi provinces of China. These results suggested that avian HEV infection may be the major cause of increased egg drop and hepatitis syndrome observed during the last 2 years in China. These results should be useful to guide development of prevention and control measures to control the diseases within chicken flocks in China. [ABSTRACT FROM AUTHOR]

Background: Fanconi-Bickel syndrome (FBS, OMIM 227810) is a rare autosomal recessive disease caused by a deficiency of glucose transporter 2 (GLUT2), a member of the facilitative glucose transporter family (Santer et al. J Inherit Metab Dis 21:191-194, 1998). The typical clinical picture is characterized by hepatorenal glycogen accumulation resulting in hepato- and nephromegaly, impaired utilization of glucose and galactose, proximal renal tubular dysfunction, rickets and severe short stature. Case presentation: We report 2 Palestinian patients from 2 families who were homozygous for the mutation p.R301X (C>T) in exon 7 of GLUT2 gene. Patient 1 showed clinical and laboratory improvement with age characterized by normal growth and resolution of rickets. Patient 2 had severe phenotype characterized by progressive weight loss, persistent metabolic acidosis, marked polyuria and clinical and laboratory findings of rickets progressing to death at age 10 months. Conclusion: This report further expands the clinical spectrum of FBS even with identical mutations. Other yet unknown genetic, environmental or stochastic factors may be responsible for phenotypic variability [ABSTRACT FROM AUTHOR]

Background: Molecular diagnosis of glycogen storage diseases (GSDs) is important to enable accurate diagnoses and make appropriate therapeutic plans. The aim of this study was to evaluate the PHKA2 mutation spectrum in Korean patients with GSD type IX. Methods: Thirteen Korean patients were tested for PHKA2 mutations using direct sequencing and a multiplex polymerase chain reaction method. A comprehensive review of the literature on previously reported PHKA2 mutations in other ethnic populations was conducted for comparison. Results: Among 13 patients tested, six unrelated male patients with GSD IX aged 2 to 6 years at the first diagnostic work-up for hepatomegaly with elevated aspartate transaminase (AST) and alanine transaminase (ALT) were found to have PHKA2 mutations. These patients had different PHKA2 mutations: five were known mutations (c.537 + 5G > A, c.884G > A [p.Arg295His], c.3210_3212delGAG [p.Arg1072del], exon 8 deletion, and exons 27-33 deletion) and one was a novel mutation (exons 18-33 deletion). Notably, the most common type of mutation was gross deletion, in contrast to other ethnic populations in which the most common mutation type was sequence variant. Conclusions: This study expands our knowledge of the PHKA2 mutation spectrum of GSD IX. Considering the PHKA2 mutation spectrum in Korean patients with GSD IX, molecular diagnostic methods for deletions should be conducted in conjunction with direct sequence analysis to enable accurate molecular diagnosis of this disease in the Korean population. [ABSTRACT FROM AUTHOR]

Background: IInterstitial 21q deletions can cause a wide spectrum of symptoms depending on the size and the location of the deletion. It has previously been suggested that the long arm of chromosome 21 can be divided into three regions based on the clinical severity of the patients and deletion of the region from 32.3 Mb to 37.1 Mb was more crucial than the deletion of other regions. Case Presentation: In this study we describe a female patient with dysmorphic features, hepatomegaly, thick myocardium and psychomotor delay. Conventional karyotyping was initially interpreted as full monosomy 21, but subsequent chromosome microarray analysis suggested an approximately 18 Mb partial monosomy. Re-evaluation of the karyotype and fluorescence in situ hybridization revealed deletion of the proximal 21q11.2-q22.11 segment and insertion of 21q22.11-qter to 12qter. The deletion of the present case overlaps with two of the proposed regions including part of the proposed crucial region. Conclusions: This report emphasizes the relevance of investigating suspected full monosomies with high resolution methods and FISH in order to investigate the extent of the deletion and the presence of more complex rearrangements. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic lymphohistiocytosis is a life-threatening disease heralded by fever, cytopenia, hepatosplenomegaly, and multisystem organ failure. Its association with genetic mutations, infections, autoimmune disorders, and malignancies is widely reported., Case Presentation: A 3-year-old male Arab Saudi patient with insignificant past medical history and parental consanguinity presented with abdominal distension of moderate severity and persistent fever despite receiving antibiotics. This was accompanied by hepatosplenomegaly and silvery hair. The clinical and biochemical profiles were suggestive of Chédiak-Higashi syndrome with hemophagocytic lymphohistiocytosis. The patient received the hemophagocytic lymphohistiocytosis-2004 chemotherapy protocol and had multiple hospital admissions mainly due to infections and febrile neutropenia. After achieving the initial remission, the patient's disease reactivated and did not respond to reinduction with the hemophagocytic lymphohistiocytosis-2004 protocol. Due to the disease reactivation and intolerance of conventional therapy, the patient commenced emapalumab. The patient was successfully salvaged and underwent an uneventful hematopoietic stem cell transplantation., Conclusions: Novel agents such as emapalumab can be helpful for the management of refractory, recurrent, or progressive disease, while avoiding the toxicities of conventional therapy. Due to a paucity of available data on emapalumab, additional data are needed to establish its role in hemophagocytic lymphohistiocytosis treatment., (© 2023. The Author(s).)

Introduction: Propofol infusion syndrome (PRIS) is a rare, but potentially lethal adverse effect of a commonly used drug. We aimed to review and correlate experimental and clinical data about this syndrome.Methods: We searched for all case reports published between 1990 and 2014 and for all experimental studies on PRIS pathophysiology. We analysed the relationship between signs of PRIS and the rate and duration of propofol infusion causing PRIS. By multivariate logistic regression we looked at the risk factors for mortality.Results: Knowledge about PRIS keeps evolving. Compared to earlier case reports in the literature, recently published cases describe older patients developing PRIS at lower doses of propofol, in whom arrhythmia, hypertriglyceridaemia and fever are less frequently seen, with survival more likely. We found that propofol infusion rate and duration, the presence of traumatic brain injury and fever are factors independently associated with mortality in reported cases of PRIS (area under receiver operator curve = 0.85). Similar patterns of exposure to propofol (in terms of time and concentration) are reported in clinical cases and experimental models of PRIS. Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose.Conclusion: PRIS can develop with propofol infusion <4 mg/kg per hour and its diagnosis may be challenging as some of its typical features (hypertriglyceridaemia, fever, hepatomegaly, heart failure) are often (>95 %) missing and others (arrhythmia, electrocardiographic changes) occur late. [ABSTRACT FROM AUTHOR]

Background: At the present, a shift from drug therapy, especially herbal therapy, to dietary supplementation is a trend in the management of dyslipidemia and related diseases. Therefore, the optimal utilization of herbal resource is important for a sustainable development of herbal medicine. Here, we compared the effects of dietary supplementation with Chinese medicine Schisandrae Chinensis Fructus seed (FSC-S) and the post-ethanol extraction residue of FSC-S (FSC-SpEt) on normal diet-fed (normal) and experimental hypercholesterolemic (HCL) mice. Methods: Male ICR mice (n = 10 in each group), weighing 17-21 g, were fed with normal diet (ND) or high cholesterol/bile salt (1/0.3 %, w/w) diet (HCBD) with or without supplemented with FSC-S, FSC-SpEt), or lipid-lowering agent fenofibrate (FF). Ten days later, serum/hepatic lipid and glucose (GLU) levels, body weight, organ/epididymal fat masses, and food/water intake were measured. Lipid level measurements included those of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), HDL/LDL ratio, LDL/HDL ratio, and non-HDL (N-HDL). Results: Supplementation with FSC-S and FSC-SpEt increased serum TC (by 64 and 25 %, respectively) and LDL (by 60 and 27 %, respectively) in normal mice. FSC-S supplementation elevated serum TC, TG, HDL, LDL, and LDL/HDL ratio (up to 64, 118, 77, 197, and 51 %, respectively) in HCL mice. FSC-SpEt supplementation reduced serum TG (by 15 %) and LDL/HDL ratio (by 18 %), as well as increased serum HDL (by 22 %) and HDL/LDL ratio (by 21 %) in HCBD-fed mice. FSC-S decreased hepatic TC (by 19 %) contents and increased hepatic TG contents by 14 % in normal mice. FSC-S reduced hepatic GLU level in both normal and HCL mice by 24 and 22 %, respectively. Hepatic TC and TG contents were lowered in FSC-SpEt-supplemented normal mice by 16 and 20 %, respectively. The body/fatty masse and food intake were lowered, but the feed efficiency index (FEI), weight gain per unit of food ingested, was increased in FSC-S-supplemented normal and HCL mice. FF supplements reduced serum/hepatic lipids, hepatic GLU contents, and epididymal fat mass, but it induced hepatomegaly and high serum alanine aminotransferase (ALT) activity in normal and/or HCL mice. Conclusion: The ensemble of results indicated that while FSC-SpEt supplementation is beneficial for the treatment of hyperlipidemia/fatty liver, FSC-S is potentially useful for the management of overweight/obesity. [ABSTRACT FROM AUTHOR]

Background: Transport protein particle (TRAPP) is a multiprotein complex involved in endoplasmic reticulum-to-Golgi trafficking. Zebrafish with a mutation in the TRAPPC11 orthologue showed hepatomegaly with steatosis and defects in visual system development. In humans, TRAPPC11 mutations have been reported in only three families showing limb-girdle muscular dystrophy (LGMD) or myopathy with movement disorders and intellectual disability. Methods: We screened muscular dystrophy genes using next-generation sequencing and performed associated molecular and biochemical analyses in a patient with fatty liver and cataract in addition to infantile-onset muscle weakness. Results: We identified the first Asian patient with TRAPPC11 mutations. Muscle pathology demonstrated typical dystrophic changes and liver biopsy revealed steatosis. The patient carried compound heterozygous mutations of a previously reported missense and a novel splice-site mutation. The splice-site change produced two aberrantly-spliced transcripts that were both predicted to result in translational frameshift and truncated proteins. Full-length TRAPPC11 protein was undetectable on immunoblotting. Conclusion: This report widens the phenotype of TRAPPC11-opathy as the patient showed the following: (1) congenital muscular dystrophy phenotype rather than LGMD; (2) steatosis and infantile-onset cataract, both not observed in previously reported patients; but (3) no ataxia or abnormal movement, clearly indicating that TRAPPC11 plays a physiological role in multiple tissues in human. [ABSTRACT FROM AUTHOR]

Purpose: To test the diagnostic power of Pocket Size Imaging Device (PSID) in detecting early signs of right heart (RH) involvement in regular smokers (RS) free of overt cardiac involvement. Methods: One-hundred-forty-three regular smokers and 51 healthy controls, comparable for age and sex, underwent physical exam (PE), PSID exam and standard echocardiography. Based on a simplified Boston score, ≥1 of clinical signs (jugular venous distension, hepatomegaly, peripheral pitting oedema and abnormal pulmonary sounds) were considered indicative of RH involvement. A composite score (1 to 4) obtained by summing the points of four quantitative RH abnormalities detectable by PSID (inferior vena cava [IVC] dilatation, reduced IVC respiratory variation, right ventricular dilatation and right atrial dilatation), was generated and ≥1 of PSID abnormal signs was considered indicative of RH involvement. Results: Boston score was not significantly different between the two groups. By using PSID, smokers exhibited greater IVC diameter (p < 0.0001), right atrial diameter (p < 0.002) and higher PSID score (p < 0.005) than controls. Compared to PE, the additional diagnostic power of PSID (≥1 abnormal sign of both Boston and PSID score) was 44.9 % in smokers. By dividing smokers in tertiles according to number of cigarettes per day, the third tertile showed the largest values of both IVC and right atrial dimension. Differences were confirmed by standard echocardiography. Reproducibility of PSID measurements and concordance of linear measurements between PSID and standard echo measurements was very good except for concordance of right ventricular basal diameter. Conclusions: PSID detects early ultrasound signs of RH involvement in regular otherwise healthy smokers in comparison with PE. [ABSTRACT FROM AUTHOR]

Background: Thorax is the common place to develop Castleman disease (CD), but there is no systemic clinical analysis for intrathoracic CD. Methods: We conducted a retrospective analysis of 48 intrathoracic CD patients with definite pathological diagnosis who were hospitalized between 1992 and 2012 in a Chinese tertiary referral hospital. Results: The study included 16 cases with unicentric CD (UCD) and 32 cases with multicentric CD (MCD). UCD were younger than MCD (30.5y vs 41.6ys, P < 0.05). MCD were more symptomatic (50% vs 96.9%, P < 0.001) and sicker than UCD, including more fever, hepatomegaly and/or splenomegaly and hypoalbuminemia. All of UCD showed solitary mass in various sites and two of them were complicated by small pleural effusion. In the MCD group, their chest CT showed obvious lymphadenopathy in the hilum and/or mediastinum (100%), diffuse parenchymal lung shadows (43.75%), pleural effusion (40.6%), mass in the mediastinum (6.25%) or hilum (3.12%) and bronchiolitis obliterans (BO) (3.12%). Besides LIP-like images, multiple nodules of different size and sites, patchy, ground-glass opacities and consolidation were showed in their chest CT. Surgery were arranged for all UCD for diagnosis and treatment and all were alive. In MCD group, superficial lymph nodes biopsies (21 cases), surgery biopsy (9 cases) and CT-guided percutaneous lung biopsy (2 cases) were performed. Hyaline vascular (HV) variant were more common in the UCD group (75% vs 37.5%, P < 0.05). In MCD group, 28 cases were prescribed with chemotherapy, one refused to receive therapy and the rest three were arranged for regular follow-up. Among MCD, 18 cases was improved, 7 cases was stable, 4 cases lost follow-up and 3 cases died. Conclusions: Intrathoracic MCD was more common than UCD in our hospital. MCD was older, more symptomic and sicker than UCD. HV variant were more common in UCD. All of UCD showed mass in various intrathoracic locations and surgery resection was performed for all and all were alive. Mass, pleural effusion, BO and diffuse pulmonary shadows, including LIP-like images, multiple nodules of different size and sites, patchy, GGO and consolidations were showed in our MCD. Most of MCD cases were arranged with chemotherapy and their prognosis were worse than UCD's. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare but life-threatening disease with confusing clinical manifestations, rapidly deteriorating health, high morbidity and mortality. Methods: To improve the recognition as well as understanding of this disorder, we analyzed clinical characteristics and prognostic factors from 85 adult patients diagnosed with HLH in our hospital from April 2005 to June 2014. Results: Patients with HLH displayed variable clinical markers across a wide spectrum. These included fever and hyperferritinemia (100%), elevated lactate dehydrogenase (LDH) (98.8%), two or three cytopenia (92.2%), splenomegaly (72.9%), hypofibrinogenemia (69.4%), hypertriglyceridemia (64.7%), hemophagocytosis (51.7%), and hepatomegaly (24.7%). Patients with active Epstien-Barr Virus (EBV) infection had a median overall survival (OS) of 65 days. Those displaying malignancy had very poor survival (median OS: 40 days). However, patients in rheumatic and non-EBV infection groups had relatively superior prognosis (not reached). Univariate analysis showed that Fibrinogen (Fbg) <1.5 g/L, platelet number (PLT) <40 × 109/L and LDH ⩾1000 U/L were factors that negatively affected survival (P = 0.004, 0.000, 0.002). Multivariate analysis showed that PLT <40 × 109/L was the independent adverse factor (HR = 0.350, 95% CI: 0.145-0.844, P = 0.019). Conclusions: HLH had very complex clinical manifestations and high death rate. Patients with active EBV infection, malignancy, Fbg <1.5 g/L, PLT <40 × 109/L and LDH ⩾1000 U/L had high risk of death as well as inferior survival, and these patients require systemic targeted treatments as early as possible. [ABSTRACT FROM AUTHOR]

Background: Avian reoviruses (ARVs) cause a range of disease presentations in domestic, captive and free-living bird species. ARVs have been reported as a cause of significant disease and mortality in free-living corvid species in North America and continental Europe. Until this report, there have been no confirmed cases of ARV-associated disease in British wild birds. Case presentation: Sporadic individual magpie (Pica pica) mortality was detected at a single site in Buckinghamshire, England, April-September 2013. An adult female magpie was found moribund and subsequently died. Post-mortem examination identified hepatomegaly and splenomegaly as the most severe macroscopic abnormalities. Histopathological examination revealed extensive hepatic and splenic necrosis. Transmission electron microscopy (TEM) identified virions of a size (circa 78 nm diameter) and morphology consistent with ARV in both the liver and the small intestinal (SI) contents. Nucleic acid extracted from pooled liver and spleen was positive on both a pan-reovirus nested PCR targeting the RNA-dependent RNA polymerase gene and a PCR using primers specific to the ARV sigma C protein gene. Virus isolated from the liver and the SI contents was characterised by a syncytial-type cytopathic effect, a reovirus-like appearance on TEM and sequence identical to that from PCR of tissues. In situ hybridisation confirmed co-localisation of ARV with lesions in the liver and spleen, implicating ARV as the causative agent. Splenic lymphoid atrophy and necrotic stomatitis associated with Aspergillus fumigatus infection were consistent with generalised immunosuppression and resultant opportunistic infection. Conclusions: The pathology and comprehensive virus investigations in this case indicate ARV as the primary pathogen in this magpie, with concurrent secondary infection subsequent to immunosuppression, as has been observed with reoviral infections in other bird species. ARV should be considered as a differential diagnosis for magpie, and potentially other corvid, disease and mortality incidents. This is the first demonstration of ARV-associated mortality in a wild bird in Britain. The prevalence and significance of ARV infection in British wild birds, and its implications for poultry and captive bird health, are currently unknown. [ABSTRACT FROM AUTHOR]

Polycystic liver disease (PLD) is the result of embryonic ductal plate malformation of the intrahepatic biliary tree. The phenotype consists of numerous cysts spread throughout the liver parenchyma. Cystic bile duct malformations originating from the peripheral biliary tree are called Von Meyenburg complexes (VMC). In these patients embryonic remnants develop into small hepatic cysts and usually remain silent during life. Symptomatic PLD occurs mainly in the context of isolated polycystic liver disease (PCLD) and autosomal dominant polycystic kidney disease (ADPKD). In advanced stages, PCLD and ADPKD patients have massively enlarged livers which cause a spectrum of clinical features and complications. Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ. Renal failure due to polycystic kidneys and non-renal extra-hepatic features are common in ADPKD in contrast to VMC and PCLD. In general, liver function remains prolonged preserved in PLD. Ultrasonography is the first instrument to assess liver phenotype. Indeed, PCLD and ADPKD diagnostic criteria rely on detection of hepatorenal cystogenesis, and secondly a positive family history compatible with an autosomal dominant inheritance pattern. Ambiguous imaging or screening may be assisted by genetic counseling and molecular diagnostics. Screening mutations of the genes causing PCLD (PRKCSH and SEC63) or ADPKD (PKD1 and PKD2) confirm the clinical diagnosis. Genetic studies showed that accumulation of somatic hits in cyst epithelium determine the rate-limiting step for cyst formation. Management of adult PLD is based on liver phenotype, severity of clinical features and quality of life. Conservative treatment is recommended for the majority of PLD patients. The primary aim is to halt cyst growth to allow abdominal decompression and ameliorate symptoms. Invasive procedures are required in a selective patient group with advanced PCLD, ADPKD or liver failure. Pharmacological therapy by somatostatin analogues lead to beneficial outcome of PLD in terms of symptom relief and liver volume reduction. [ABSTRACT FROM AUTHOR]