• 16sRNA
• S. japonicum infection
• gut microbiome
• splenectomy

• Splenectomy
• Schistosomiasis japonica/surgery
• Schistosomiasis japonica/microbiology
• Gastrointestinal Microbiome
• Humans
• Female
• Middle Aged
• Male
• Animals
• Adult
• Schistosoma japonicum
• RNA, Ribosomal, 16S/genetics
• Dysbiosis
• Aged

• National Natural Science Foundation of China
• National Natural Science Foundation of China

• Cestodes
• Liver flukes
• Nematodes
• Parasites
• Protozoa
• Trematodes

• Humans
• Animals
• Liver Diseases, Parasitic/epidemiology
• Liver Diseases, Parasitic/parasitology
• Liver Diseases, Parasitic/diagnosis
• Liver Diseases, Parasitic/therapy
• Liver/parasitology
• Endemic Diseases/statistics & numerical data
• Endemic Diseases/prevention & control
• Global Health

• Autoimmune overlap syndrome
• IgG4-related disease
• Primary sclerosing cholangitis
• Secondary sclerosing cholangitis

• Humans
• Cholangitis, Sclerosing/diagnosis
• Cholangitis, Sclerosing/complications
• Diagnosis, Differential
• Bile Ducts
• Autoimmune Diseases
• Phenotype

• bilharzia
• intervention coverage
• mass drug administration
• praziquantel chemotherapy
• schistosomiasis
• uptake

• Calcified Eggs
• Dilation of Bile Duct
• Schistosomiasis

• cestodes
• helminths
• immunity
• nematodes
• non-communicable diseases
• trematodes

• Biomarkers
• Elasticity imaging techniques
• Liver fibrosis
• Parasitic liver diseases
• Schistosoma mansoni
• Ultrasonography

• GABA
• Granuloma diameter
• Granuloma number
• Oxidative stress
• Praziquantel
• Schistosoma mansoni

• Advanced schistosomiasis
• Machine learning
• Prognosis
• XGBoost

Hepatic infections are frequent in clinical practice. Although epidemiological, clinical and laboratory data may suggest hepatic infection in certain cases, imaging is nearly always necessary to confirm the diagnosis, assess disease extension and its complications, evaluate the response to treatment, and sometimes to make differential diagnoses such as malignancies. Ultrasound (US) is usually the first-line investigation, while computed tomography (CT) and magnetic resonance imaging (MRI) provide better characterization and a more precise assessment of local extension, especially biliary and vascular. The purpose of this article is to describe the typical features and main complications of common hepatic infections. Familiarity with the radiological features of this entity can help suggest the correct diagnosis and the need for further studies as well as determine appropriate and timely treatment.

• Hepatic infection
• Liver imaging
• Liver infection

Schistosomiasis is a trematode infection rarely diagnosed in the United States. Intestinal involvement is common with chronic infection and causes abdominal pain, changes in bowel habits, hematochezia, and polyp formation. Chronic, disseminated infection can affect the intestines causing the aforementioned symptoms, but reports of intestinal polyps are rare. Most cases are inflammatory fibrous polyps in the colon. There are very few cases reported in the literature of hamartomatous polyps arising in the small intestine. We present the rare case of a U.S.-born, 35-year-old woman diagnosed with a large duodenal hamartomatous polyp in the setting of intestinal schistosomiasis.

• Animals
• DNA Methylation
• Epigenesis, Genetic
• Female
• Gene Expression Regulation/immunology
• Liver/metabolism
• Liver/parasitology
• Male
• Mice
• Mice, Knockout
• MicroRNAs
• Minor Histocompatibility Antigens/genetics
• RNA, Helminth/genetics
• RNA, Helminth/metabolism
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Receptors, Cytokine/genetics
• Schistosoma mansoni/immunology
• Schistosomiasis mansoni/immunology
• Schistosomiasis mansoni/parasitology

• CNPq

• clinical imaging
• hepatosplenic schistosomiasis
• liver fibrosis
• portal hypertension
• preclinical imaging
• quantitative imaging methods

Macrophages play central roles in inflammatory reactions and initiation of immune responses during infections. More than 80% of total tissue macrophages are described to be located in the liver as liver-resident macrophages, also named Kupffer cells (KCs). While studies in mice have established a central role of liver-resident KCs in regulating liver inflammation, their phenotype and function are not well-characterized in humans. Comparing paired human liver and peripheral blood samples, we observed significant differences in the distribution of macrophage (Mφ) subsets, with lower frequencies of CD14^hiCD16^lo and higher frequencies of CD14^int−hiCD16^int Mφ in human livers. Intrahepatic Mφ consisted of diverse subsets with differential expression of CD49a, a liver-residency marker previously described for human and mice NK cells, and VSIG4 and/or MARCO, two recently described human tissue Mφ markers. Furthermore, intrahepatic CD49a⁺ Mφ expressed significantly higher levels of maturation and activation markers, exhibited higher baseline levels of TNF-α, IL-12, and IL-10 production, but responded less to additional in vitro TLR stimulation. In contrast, intrahepatic CD49a⁻ Mφ were highly responsive to stimulation with TLR ligands, similar to what was observed for CD49a⁻ monocytes (MOs) in peripheral blood. Taken together, these studies identified populations of CD49a⁺, VSIG4⁺, and/or MARCO⁺ Mφ in human livers, and demonstrated that intrahepatic CD49a⁺ Mφ differed in phenotype and function from intrahepatic CD49a⁻ Mφ as well as from peripheral blood-derived monocytes.

• CD49a
• cell activation
• human liver
• monocytes/macrophages
• tissue residency

L-praziquantel (PZQ) pharmacokinetic data were analyzed from two relative bioavailability Phase 1 studies in adult, healthy subjects with two new oral dispersion tablet (ODT) formulations of L-PZQ administered under various combinations of co-administration with food, water, and/or crushing. Linear mixed effects models adequately characterized the noncompartmental estimates of the pharmacokinetic profiles in both studies. Dose, food, and formulation were found to significantly affect L-PZQ exposure in both studies. The model for AUC was then extrapolated to children 2–5 years old accounting for enzyme maturation and weight. The predicted exposures were compared to an external Phase 1 study conducted by the Swiss Tropical and Public Health Institute using a currently marketed formulation (Cesol 600 mg immediate-release tablets) and found to be substantially lower than observed. A root cause analysis was completed to identify the reason for failure of the models. Various scenarios were proposed and tested. Two possible reasons for the failure were identified. One reason was that the model did not account for the reduced hepatic clearance seen in patients compared to the healthy volunteer population used to build the model. The second possible reason was that PZQ absorption appears sensitive to meal composition and the model did not account for differences in meals between a standardized Phase 1 unit and clinical sites in Africa. Further studies are needed to confirm our hypotheses.

• Complex pharmacokinetics
• Linear mixed effects models
• NONMEM
• Oral dispersion tablet
• Population pharmacokinetics
• Root cause analysis

In chronic schistosomiasis, liver fibrosis is linked to portal hypertension, which is a condition associated with high mortality and morbidity. High mobility group box 1 (HMGB1) was originally described as a nuclear protein that functions as a structural co-factor in transcriptional regulation. However, HMGB1 can also be secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 acts as a multifunctional cytokine that contributes to infection, injury, inflammation, and immune responses by binding to specific cell-surface receptors. HMGB1 is involved in fibrotic diseases. From a clinical perspective, HMGB1 inhibition may represent a promising therapeutic approach for treating tissue fibrosis. In this study, we demonstrate elevated levels of HMGB1 in the sera in experimental mice or in patients with schistosomiasis. Using immunohistochemistry, we demonstrated that HMGB1 trafficking in the hepatocytes of mice suffering from acute schistosomiasis was inhibited by Glycyrrhizin, a well-known HMGB1 direct inhibitor, as well as by DIC, a novel and potential anti-HMGB1 compound. HMGB1 inhibition led to significant downregulation of IL-6, IL4, IL-5, IL-13, IL-17A, which are involved in the exacerbation of the immune response and liver fibrogenesis. Importantly, infected mice that were treated with DIC or GZR to inhibit HMGB1 pro-inflammatory activity showed a significant increase in survival and a reduction of over 50% in the area of liver fibrosis. Taken together, our findings indicate that HMGB1 is a key mediator of schistosomotic granuloma formation and liver fibrosis and may represent an outstanding target for the treatment of schistosomiasis.

• HMGB1
• drugs therapy
• granuloma
• liver fibrosis
• schistosomiasis

• Colorectal cancer
• Complication
• Laparoscopic surgery
• Liver cirrhosis
• Survival

The immune system protects the organism from foreign invaders and foreign substances and is involved in physiological functions that range from tissue repair to neurocognition. However, an excessive or dysregulated immune response can cause immunopathology and disease. A 39-year-old man was affected by severe hepatosplenic schistosomiasis mansoni and by amyotrophic lateral sclerosis. One question that arose was, whether there was a relation between the parasitic and the neurodegenerative disease. IL-17, a proinflammatory cytokine, is produced mainly by T helper-17 CD4 cells, a recently discovered new lineage of effector CD4 T cells. Experimental mouse models of schistosomiasis have shown that IL-17 is a key player in the immunopathology of schistosomiasis. There are also reports that suggest that IL-17 might have an important role in the pathogenesis of amyotrophic lateral sclerosis. It is hypothesized that the factors that might have led to increased IL-17 in the hepatosplenic schistosomiasis mansoni might also have contributed to the development of amyotrophic lateral sclerosis in the described patient. A multitude of environmental factors, including infections, xenobiotic substances, intestinal microbiota, and vitamin D deficiency, that are able to induce a proinflammatory immune response polarization, might favor the development of amyotrophic lateral sclerosis in predisposed individuals.

The portal vein carries blood from the gastrointestinal tract to the liver and in so doing carries microbes as well. The liver may therefore be involved in infections with a myriad number of microbial organisms. While some of these infections most commonly occur in the immunocompromised host, others affect the immune competence. Hepatic infections may be primary in nature or secondary, as part of systemic or contagious disease. The purpose of this chapter is to provide a brief overview of the various infections of the liver in the pediatric patient.

• esophageal varices
• noninvasive
• platelet count/spleen diameter ratio
• portal hypertension
• schistosomiasis

• Animals
• Endocarditis/diagnosis
• Endocarditis/etiology
• Endocarditis/parasitology
• Humans
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/etiology
• Liver Cirrhosis/parasitology
• Male
• Middle Aged
• Schistosoma japonicum
• Schistosomiasis japonica/complications
• Schistosomiasis japonica/diagnosis

• Animals
• Child
• China
• Female
• Humans
• Longitudinal Studies
• Male
• Observer Variation
• Parasite Egg Count
• Prospective Studies
• Schistosoma japonicum/isolation & purification
• Schistosomiasis/diagnostic imaging
• Schistosomiasis/parasitology
• Schistosomiasis/physiopathology
• Ultrasonography

• R01 AI050612 NIAID NIH HHS
• R01 AI-50612-5 NIAID NIH HHS