Alveolar Echinococcosis Patients Research Articles

Immunological Characteristics of Hepatic Dendritic Cells in Patients and Mouse Model with Liver Echinococcus multilocularis Infection

The cestode Echinococcus multilocularis, which mainly dwells in the liver, leads to a serious parasitic liver disease called alveolar echinococcosis (AE). Despite the increased attention drawn to the immunosuppressive microenvironment formed by hepatic AE tissue, the immunological characteristics of hepatic dendritic cells (DCs) in the AE liver microenvironment have not been fully elucidated. Here, we profiled the immunophenotypic characteristics of hepatic DC subsets in both clinical AE patients and a mouse model. Single-cell RNA sequencing (scRNA-Seq) analysis of four AE patient specimens revealed that greater DC numbers were present within perilesional liver tissues and that the distributions of cDC and pDC subsets in the liver and periphery were different. cDCs highly expressed the costimulatory molecule CD86, the immune checkpoint molecule CD244, LAG3, CTLA4, and the checkpoint ligand CD48, while pDCs expressed these genes at low frequencies. Flow cytometric analysis of hepatic DC subsets in an E. multilocularis infection mouse model demonstrated that the number of cDCs significantly increased after parasite infection, and a tolerogenic phenotype characterized by a decrease in CD40 and CD80 expression levels was observed at an early stage, whereas an activated phenotype characterized by an increase in CD86 expression levels was observed at a late stage. Moreover, the expression profiles of major immune checkpoint molecules (CD244 and LAG3) and ligands (CD48) on hepatic DC subsets in a mouse model exhibited the same pattern as those in AE patients. Notably, the cDC and pDC subsets in the E. multilocularis infection group exhibited higher expression levels of PD-L1 and CD155 than those in the control group, suggesting the potential of these subsets to impair T cell function. These findings may provide valuable information for investigating the role of hepatic DC subsets in the AE microenvironment and guiding DC targeting treatments for AE.

Epidemiology and Clinical Characteristics of Cerebral Alveolar Echinococcosis in the Tibetan Region of Sichuan, China.

This study aimed to examine the epidemiology and clinical characteristics of cerebral alveolar echinococcosis in the Tibetan region of Sichuan, China. A retrospective analysis of hospitalized cases of cerebral alveolar echinococcosis from six medical units in the Garze Tibetan Autonomous Prefecture, Sichuan Province, from January 2016 to June 2021 was conducted. The study focused on the characteristics, clinical presentation, and imaging features of the disease. Of 119 cerebral alveolar echinococcosis patients, 76 were male and 43 were female. Occupationally, 62 were farmers, 46 were herdsmen, nine were monks, and two were students. The mean age was 43.9 (± 13.9) years. The primary clinical manifestations were dizziness, headaches, and epilepsy. The incidence of cerebral alveolar echinococcosis was most concentrated within 4 years after the diagnosis of hepatic alveolar echinococcosis (77/119, 64.7%). There were 86 cases (72.3%) with multiple intracranial echinococcosis lesions, with an average size of 2.0 cm × 2.5 cm. The imaging features showed that the lesion was mainly concentrated in the anterior circulation blood supply area, and the lesion had multiple aggregated small vesicular structures as its unique imaging feature. Among 98 follow-up cases, 62 could live independently (63.3%); 18 deaths were recorded (18.4%), with an approximate 5-year survival rate of 81.6%. Regular examination of patients with first diagnosis of hepatic alveolar echinococcosis without a combination of echinococcosis in other parts of the body can help monitor and prevent the occurrence of cerebral alveolar echinococcosis, improve the understanding of cerebral alveolar echinococcosis in Tibetan areas of Sichuan.

The expression of CTLA-4 in hepatic alveolar echinococcosis patients and blocking CTLA-4 to reverse T cell exhaustion in Echinococcus multilocularis-infected mice.

Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by the infection of Echinococcus multilocularis (E. multilocularis) larvae. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) produces inhibitory signals and induces T cell exhaustion, thereby inhibiting the parasiticidal efficacy of the liver immune system. Therefore, the purpose of this study is to explore how T-cell exhaustion contributes to AE and whether blocking CTLA-4 could reverse T cell exhaustion. Here we discovered that the expression of CTLA-4 was increased in the infiltrating margin around the lesion of the liver from AE patients by using western blot and immunohistochemistry assay. Multiple fluorescence immunohistochemistry identified that CTLA-4 and CD4/CD8 molecules were co-localized. For in vitro experiments, it was found that the sustained stimulation of E. multilocularis antigen could induce T cell exhaustion, blocking CTLA-4-reversed T cell exhaustion. For in vivo experiments, the expression of CTLA-4 was increased in the liver of E. multilocularis-infected mice, and the CTLA-4 and CD4/CD8 molecules were co-localized. Flow cytometry analysis demonstrated that the percentages of both CD4+ T cells and CD8+ T cells in the liver and peripheral blood were significantly increased and induced T exhaustion. When the mice were treated with anti-CTLA-4 antibodies, the number and weight of the lesions decreased significantly. Meanwhile, the flow cytometry results suggested that blocking CTLA-4 could effectively reverse T cell exhaustion and reactivate immune function. Our work reveals that blocking CTLA-4 could effectively reverse the T cell exhaustion caused by E. multilocularis and could be used as a novel target for the treatment of AE.

Phenotype and function of MAIT cells in patients with alveolar echinococcosis.

Mucosal-associated invariant T (MAIT) cells are a subpopulation of unconventional T cells widely involved in chronic liver diseases. However, the potential role and regulating factors of MAIT cells in alveolar echinococcosis (AE), a zoonotic parasitic disease by Echinococcus multilocularis (E. multilocularis) larvae chronically parasitizing liver organs, has not yet been studied. Blood samples (n=29) and liver specimens (n=10) from AE patients were enrolled. The frequency, phenotype, and function of MAIT cells in peripheral blood and liver tissues of AE patients were detected by flow cytometry. The morphology and fibrosis of liver tissue were examined by histopathology and immunohistochemistry. The correlation between peripheral MAIT cell frequency and serologic markers was assessed by collecting clinicopathologic characteristics of AE patients. And the effect of in vitro stimulation with E. multilocularis antigen (Emp) on MAIT cells. In this study, MAIT cells are decreased in peripheral blood and increased in the close-to-lesion liver tissues, especially in areas of fibrosis. Circulating MAIT exhibited activation and exhaustion phenotypes, and intrahepatic MAIT cells showed increased activation phenotypes with increased IFN-γ and IL-17A, and high expression of CXCR5 chemokine receptor. Furthermore, the frequency of circulating MAIT cells was correlated with the size of the lesions and liver function in patients with AE. After excision of the lesion site, circulating MAIT cells returned to normal levels, and the serum cytokines IL-8, IL-12, and IL-18, associated with MAIT cell activation and apoptosis, were altered. Our results demonstrate the status of MAIT cell distribution, functional phenotype, and migration in peripheral blood and tissues of AE patients, highlighting their potential as biomarkers and therapeutic targets.

Molecular analyses of exosome-derived miRNAs revealed reduced expression of miR-184-3p and decreased exosome concentration in patients with alveolar echinococcosis

Both E. multilocularis and host-derived exosomes are involved in the pathogenic process of alveolar echinococcosis (AE). Exosomes secrete miRNAs that have regulatory roles in host-pathogen interactions in multiple ways. In the present study, we collected and purified supernatants of E. multilocularis cultures, as well as human plasma exosomes. High-throughput sequencing showed the identities of 45 exosomal miRNAs in E. multilocularis. The lengths of these miRNAs ranged from 19 to 25 nucleotides (nt), with the majority (n = 18) measuring 22 nt. Notably, emu-let-7-5p emerged as the most abundant among these miRNAs, with a detected count of 33,097 and also length of 22 nt. Nanoparticle tracking analysis (NTA) showed that the concentration of exosomes in the plasma of AE patients was lower compared to that in the healthy individuals. This result suggested that the concentration of plasma exosomes was able to distinguish AE patients from healthy individuals. Using qRT-PCR to assess the relative expression of 10 miRNAs of E. multilocularis, we showed that the expression of miR-184-3p was downregulated significantly in the exosomes of plasma from AE patients compared to that in the control group. In summary, this study indicates that AE induces a reduction in the concentration of human plasma exosomes, as well as downregulating miR-184-3p in infected individuals.

Identification and exploration of a new M2 macrophage marker MTLN in alveolar echinococcosis

The pathogen of alveolar echinococcosis (AE) is Echinococcus multilocularis (E. multilocularis), which has the characteristics of diffuse infiltration and growth and has a high mortality rate. At present, the role of macrophages in AE infection has attracted more and more attention, but the new biomarkers and polarization mechanisms of macrophages are rarely studied. In this study, CIBERSORT and WGCNA algorithms were used to establish a weighted gene co-expression network, and MTLN was identified as a biological marker of M2-type macrophages, which participated in energy metabolism of macrophages and mediated inflammatory response, but the role of MTLN in AE was not studied. In this study, liver tissue samples from AE patients were collected and immunofluorescence co-localization showed the relationship between MTLN and macrophage distribution. E. multilocularis infected mouse model was established to analyze the expression of MTLN, liver fibrosis, and inflammatory reaction after E. multilocularis infection. The cell experiment simulated the liver microenvironment of E. multilocularis infected human body and analyzed the expression of MTLN by QRT-PCR and western blot in vitro. The data showed that liver fibrosis occurred in AE patients, and MTLN was activated near the focus. After E. multilocularis infected mice, the expression of MTLN increased with time. In the cell experiment, after the antigen of E. multilocularis protoscolex stimulated normal liver cells, the expression of MTLN increased 48 h, at this time, M2 was up-regulated and M1 was down-regulated. Therefore, MTLN may be the key gene to regulate the polarization of M2 macrophages and cause fibrosis.

Genetic diversity of Echinococcus multilocularis specimens isolated from Belgian patients with alveolar echinococcosis using EmsB microsatellites analysis

The genetic diversity of Echinococcus multilocularis (E. multilocularis) specimens isolated from patients with alveolar echinococcosis (AE), is a major field of investigation to correlate with sources of infection, clinical manifestations and prognosis of the disease. Molecular markers able to distinguish samples are commonly used worldwide, including the EmsB microsatellite. Here, we report the use of the EmsB microsatellite polymorphism data mining for the retrospective typing of Belgian specimens of E. multilocularis infecting humans. A total of 18 samples from 16 AE patients treated between 2006 and 2021 were analyzed through the EmsB polymorphism. Classification of specimens was performed through a dendrogram construction in order to compare the similarity among Belgian samples, some human referenced specimens on the EWET database (EmsB Website for the Echinococcus Typing) and previously published EmsB profiles from red foxes circulating in/near Belgium. According to a comparison with human European specimens previously genotyped in profiles, the 18 Belgian ones were classified into three EmsB profiles. Four specimens could not be assigned to an already known profile but some are near to EWET referenced samples. This study also highlights that some specimens share the same EmsB profile with profiles characterized in red foxes from north Belgium, the Netherlands, Luxembourg and French department near to the Belgian border. Furthermore, Belgian specimens present a genetic diversity and include one profile that don't share similarities with the ones referenced in the EWET database. However, at this geographical scale, there is no clear correlation between EmsB profiles and geographical location. Further studies including additional clinical samples and isolates from foxes and rodents of south Belgium are necessary to better understand the spatial and temporal circumstances of human infections but also a potential correlation between EmsB profiles and parasite virulence.

[Clinical Features and Surgical Outcomes of 15 Cases of Intracranial Alveolar Echinococcosis].

To investigate the surgical treatment strategy of intracranial alveolar echinococcosis (AE) and the clinical outcomes. The clinical and follow-up data of 15 intracranial AE patients who underwent surgical treatment in the Departments of Neurosurgery of Sichuan Provincial People's Hospital (SPPH) and People's Hospital of Aba Tibetan and Qiang Autonomous Prefecture (a branch hospital of SPPH) between March 2017 and January 2021 were retrospectively analyzed. Full follow-up data were available for each of the 15 cases. The clinical and imaging characteristics, general surgical information, and surgical outcomes were analyzed. In the 15 patients, there were a total of 50 intracranial lesions, with an average of (3.3±3.1)/case. Four cases had solitary intracranial lesions, while 11 cases had multiple lesions, with the number of intracranial lesions per case ranging from 2 to 13. All patients with solitary intracranial lesions received total resection. In 6 patients with multiple intracranial lesions, only the largest lesion was surgically removed, and in 5 patients, 2 to 3 adjacent lesions were surgically removed. All but one patient had extracranial lesions in their liver, lungs, kidneys, adrenal glands, and thoracic vertebrae. The patients were followed up for 12 to 58 months after surgery, with the mean follow-up time being (28.1±13.4) months. Among the 15 cases, 13 showed stable intracranial condition during postoperative follow-up. Intracranial lesions recurred in 2 patients who had deep lesions accompanied by dissemination to the subarachnoid space. Two patients died during follow-up. Microsurgical treatment of intracranial AE is effective, but total surgical resection is difficult to accomplish when patients have echinococcosis lesions located at a depth, especially when the lesions are spreading to the subarachnoid space. The prognosis of patients is closely associated with the extent of lesion invasion and the control of systemic hydatid lesions, especially those in the liver.

Integrative analysis of serum-derived exosomal lncRNA profiles of alveolar echinococcosis patients

Alveolar echinococcosis is a severe zoonotic disease caused by the pseudotumoral intrahepatic development of the larval stage of the tapeworm Echinococcus multilocularis. The diagnosis of alveolar echinococcosis is hard since it has features of liver cancer. LncRNAs are among the non-coding RNAs that have received the most attention in recent biomarker studies. Here, we aimed to identify the serum-derived exosomal lncRNAs associated with alveolar echinococcosis in humans with RNA-seq. After RNA isolation from exosomes, we performed RNA-seq to determine the lncRNAs. We found 8 target genes in the cis direction and a total of 6468 gene targets for lncRNAs were identified in the trans direction. Totally 621 mRNA transcripts were found as differentially expressed between the controls and patients. 278 of them were up-regulated and 343 were down-regulated. Moreover, 234 lncRNAs were found as differentially expressed between the controls and patients. 58 of them were up-regulated, and 176 of them were down-regulated. The top five biological pathways regulated by identified lncRNAs were detected in this study. As a result, it is thought that these results will contribute to lncRNA-based biomarker studies that can be used in the early diagnosis of alveolar echinococcosis in humans.

Management of biliary obstruction in patients with newly diagnosed alveolar echinococcosis: a Swiss retrospective cohort study.

Alveolar echinococcosis, an orphan zoonosis affecting the liver, is of increasing concern worldwide. Most symptomatic cases present at an advanced and inoperable stage, sometimes with biliary obstruction prompting biliary tract interventions. These are, however, associated with a high risk of infectious complications. The aim of this retrospective study was to compare the effectiveness and safety of conservative and interventional treatment approaches in patients with newly diagnosed alveolar echinococcosis and biliary obstruction. Alveolar echinococcosis patients treated at two referral centres in Switzerland, presenting with hyperbilirubinaemia (total bilirubin >1.5 Upper Limit of Normal) at diagnosis were included, unless another underlying aetiology, i.e. common bile duct stones or decompensated cirrhosis, was identified. Patients were divided into two groups, according to whether they initially received a biliary tract intervention. The primary endpoint was normalisation of bilirubin levels within a 6-month period. Secondary endpoints included, among others, the occurrence of early and late biliary complications, the need for biliary tract interventions during follow-up and overall duration of hospital stays for treatment initiation and for biliary complications. 28 patients were included in this study, of whom 17 received benzimidazole therapy alone and 11 additionally received a biliary tract intervention. Baseline characteristics did not differ between groups. All but one patient in each group achieved the primary endpoint (p=0.747). Biliary tract intervention was associated with faster laboratory improvement (t1/21.3 vs 3.0 weeks), but also with more frequent early biliary complications (7/11 vs 1/17, p=0.002) and longer initial hospital stay (18 days vs 7 days, p=0.007). Biliary obstruction in patients with newly diagnosed alveolar echinococcosis can be treated effectively with benzimidazole therapy alone. Biliary tract intervention, on the other hand, is associated with a high complication rate and should probably be reserved for patients with insufficient response to benzimidazole therapy.

Detection of Asian genetic components in autochthonous human Echinococcus multilocularis infections from endemic Warmia-Masuria (north-eastern Poland)

Alveolar echinococcosis is a life-threatening zoonotic disease caused by the larval stage of the cestode Echinococcus multilocularis. People are aberrant intermediate hosts accidentally infected with the parasite eggs via faecal-oral route, usually by the consumption of unwashed fruit and vegetable or direct contact with definitive hosts. The recently reported presence of Asian admixture in E. multilocularis tapeworms from Polish red foxes prompted the question of metacestode descent in the human population. In this study, a Maximum Likelihood tree based on partial sequences of E. multilocularis mitochondrial genes cox1, cob, and nad2 coupled with a hierarchical clustering analysis of microsatellite EmsB profiles and supplemented by Sammon's nonlinear mapping with k-means clustering revealed Asian genetic components, to date associated only with the sylvatic cycle, in two autochthonous samples from alveolar echinococcosis patients living in endemic Warmia-Masuria, north-eastern Poland. The red fox is the most likely source of contamination in the environment shared by people and wildlife that led to these infections. Our results confirm that Asian genetic variants participate in the synanthropic cycle in north-eastern Poland and indicate that they may be present in the human population in other areas where Asian genetic variants were detected in red foxes.

18FDG-PET/CT-Scans and Biomarker Levels Predicting Clinical Outcome in Patients with Alveolar Echinococcosis-A Single-Center Cohort Study with 179 Patients.

Background: Alveolar echinococcosis (AE) is a severe larval tapeworm infection with a variable clinical course of the disease. Reliable imaging techniques and biomarkers are needed to predict the course of the disease. Methods: 179 AE patients that received PET/CT scans between 2008 and 2012 were retrospectively included. From stored blood samples taken on the day of the scan, levels of IgE, parasite-specific serology, amyloid A, C-reactive protein, soluble interleukin 2 receptor, cytokeratin fragments, eosinophilic cell count, and eosinophil cationic protein were measured. Additionally, the current clinical outcome (cured, stable, or progressive disease) after a median duration of 8 years after baseline examination was assessed. Ultimately, an ordinal logistic regression was conducted to evaluate which imaging parameters and biomarkers independently influence the clinical outcome. Results: In general, patients in need of medical treatment or with progressive disease, advanced PNM stages, and positive PET/CT scans exhibited higher levels of the respective biomarkers. However, only the parasite-specific serological markers and total IgE levels differed significantly between clinical groups, WHO PNM stages, and the results of the PET/CT scan. In the multivariate analysis, PET/CT results were a strong predictor of the clinical outcome (OR 8.908, 95%CI 3.019-26.285; p < 0.001), and age at baseline was a moderate predictor (OR 1.031, 95%CI 1.003-1.060; p = 0.029). Conclusions: The PET/CT scan is, preferably in combination with parasite-specific serology and IgE levels, a valuable tool in the clinical management of AE and is able to predict the course of the disease.

Understanding Alveolar echinococcosis patients' psychosocial burden and coping strategies-A qualitative interview study.

Alveolar echinococcosis (AE) is a serious parasitic zoonotic disease that resembles malignancy with clinically silent infiltrative growth predominantly involving the liver. AE patients show high levels of comorbid psychological burden and fear of disease progression. This study aimed to examine AE patients' perspective on their disease-related psychosocial burden using qualitative methods. We conducted N = 12 semi-structured interviews with AE patients focusing on their disease-related psychosocial burden, coping strategies, information seeking behavior, and subjective illness concepts. To this end, AE patients from a previous quantitative cross-sectional study were invited to participate. After verbatim transcription, interviews were analyzed thematically. After analysis, data was grouped into five main themes: A) Perceived disease-related burden, B) Coping with disease-related burden, C) Disease-related impact on their social environment, D) Facing the future with the disease, and E) Disease-related information seeking behavior and subjective illness concepts. All participants perceived AE as a severe disease with inextricably linked biological, psychological, and social effects. Key positive influences reported included the provision of information and access to informal and formal support, including the ability to lead active personal and professional lives for as long as possible. Self-directed, web-based information seeking often led to increased feelings of hopelessness and anxiety. Our findings underscore the need to consider psychosocial morbidity in AE patient management. To reduce psychological burden, address disease-related apprehensions, and to prevent stigmatization, health professionals need to provide AE patients with comprehensive disease-related information to improve patient and social awareness.

Upregulation of LAG3 modulates the immune imbalance of CD4+ T-cell subsets and exacerbates disease progression in patients with alveolar echinococcosis and a mouse model.

Infection with the cestode Echinococcus multilocularis (E. multilocularis) causes alveolar echinococcosis (AE), a tumor-like disease predominantly affecting the liver but able to spread to any organ. T cells develop functional defects during chronic E. multilocularis infection, mostly due to upregulation of inhibitory receptors such as T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) and programmed death-1 (PD-1). However, the role of lymphocyte activation gene-3 (LAG3), an inhibitory receptor, in AE infection remains to be determined. Here, we discovered that high expression of LAG3 was mainly found in CD4+ T cells and induced regulatory T cells (iTregs) in close liver tissue (CLT) from AE patients. In a mouse model of E. multilocularis infection, LAG3 expression was predominantly found in T helper 2 (Th2) and Treg subsets, which secreted significantly more IL-4 and IL-10, resulting in host immune tolerance and disease progression at a late stage. Furthermore, LAG3 deficiency was found to drive the development of effector memory CD4+ T cells and enhance the type 1 CD4+ T-cell immune response, thus inhibiting metacestode growth in vivo. In addition, CD4+ T cells from LAG3-deficient mice produced more IFN-γ and less IL-4 when stimulated by E. multilocularis protoscoleces (EmP) antigen in vitro. Finally, adoptive transfer experiments showed that LAG3-knockout (KO) CD4+ T cells were more likely to develop into Th1 cells and less likely to develop into Tregs in recipient mice. Our work reveals that high expression of LAG3 accelerates AE disease progression by modulating the immune imbalance of CD4+ T-cell subsets. These findings may provide a novel immunotherapeutic strategy against E. multilocularis infection.

NOTCH signaling inhibition after DAPT treatment exacerbates alveolar echinococcosis hepatic fibrosis by blocking M1 and enhancing M2 polarization.

Alveolar echinococcosis (AE) is a lethal helminthic liver disease caused by persistent infection with Echinococcus multilocularis (E. multilocularis). Although more and more attention has been paid to the macrophages in E. multilocularis infection, the mechanism of macrophage polarization, a critical player in liver immunity, is seldom studied. NOTCH signaling is involved in cell survival and macrophage-mediated inflammation, but the role of NOTCH signaling in AE has been equally elusive. In this study, liver tissue samples from AE patients were collected and an E. multilocularis infected mouse model with or without blocking NOTCH signaling was established to analyze the NOTCH signaling, fibrotic and inflammatory response of the liver after E. multilocularis infection. Changes in polarization and origin of hepatic macrophages were analyzed by flow cytometry. In vitro qRT-PCR and Western blot assays were performed to analyze key receptors and ligands in NOTCH signaling. Our data demonstrated that hepatic fibrosis develops after AE, and the overall blockade of NOTCH signaling caused by DAPT treatment exacerbates the levels of hepatic fibrosis and alters the polarization and origin of hepatic macrophages. Blocking NOTCH signaling in macrophages after E. multilocularis infection downregulates M1 and upregulates M2 expression. The downregulation of NTCH3 and DLL-3 in the NOTCH signaling pathway is significant. Therefore, NOTCH3/DLL3 may be the key pathway in NOTCH signaling regulating macrophage polarization affecting fibrosis caused by AE.

Metabolomic profiling of early inactive hepatic alveolar and cystic echinococcosis

Hepatic alveolar echinococcosis (AE) and cystic echinococcosis (CE) are severe helminthic zoonoses and leading causes of parasitic liver damage. They pose a high mortality risk due to invisible clinical signs, especially at the early inactive stage. However, the specific metabolic profiles induced by inactive AE and CE lesions remain largely unclear. Therefore, we used gas chromatography-mass spectrometry-based metabolomic profiling to identify the global metabolic variations in AE and CE patient sera to differentiate between the two diseases and reveal the mechanisms underlying their pathogenesis. In addition, specific serum biomarkers of inactive hepatic AE and CE were screened using receiver operating curves, which can contribute to the clinical diagnosis of both diseases, especially in the earlier phase. These differential metabolites are involved in glycine, serine, tyrosine, and phenylalanine metabolism. Further analysis of key metabolic pathways showed that inactive AE lesions strongly alter amino acid metabolism in the host. CE lesions have an altered metabolism of oxidative stress response. These changes suggest these metabolite-associated pathways can serve as biomarkers to distinguish individuals with inactive AE and CE from healthy populations. This study also investigated the differences in serum metabolic profiles in patients with CE and AE. The biomarkers identified belonged to different metabolic pathways, including lipid, carnitine, androgen, and bile acid metabolism. Taken together, by investigating the different phenotypes of CE and AE with metabolomic profiling, serum biomarkers facilitating early diagnosis were identified.

[Diagnostic delaying factors in hepatic alveolar echinococcosis].

The purpose of this study was to analyze the diagnostic workflow of patients with alveolar echinococcosis (AE) and to identify possible diagnosis-delaying factors. The number and type of diagnostic procedures of patients diagnosed with alveolar echinococcosis were investigated. The disease history was recorded on the basis of questionnaires, the available findings, and data supplements from the hospital information system (SAP). Statistical analyses were performed using SAS version 9.4 and Microsoft Excel version 16.43. The study population of the cross-sectional study included n = 109 patients with confirmed alveolar echinococcosis. The definitive diagnosis of alveolar echinococcosis of the liver was made at 26.5 ± 65.0 (mean ± standard deviation) months (min - max: 0 - 344, median = 3). The majority of patients were diagnosed because of incidental imaging findings of the liver (n = 74/109 (67.9%)). A total of n = 56/74 (75.7%) of all incidental findings were diagnosed in an outpatient setting, while n = 15/74 (20.3%) of cases were diagnosed during inpatient hospitalization. On average, 1.1 ± 1.2 (0-11, median = 1) ionizing imaging modalities were used for each patient. Contrast-enhanced sonography was received by 0.3 ± 0.5 (0-2, median = 0) patients. Almost all patients (n = 104/109 (95.4%) had at least one suspected hepatic or extrahepatic malignancy at some time. Exclusion of suspected malignancy occurred at a mean of 4.1 ± 16.5 months (0 -133.8, median = 1). The diagnostic clarification process of AE patients is lengthy and stressful. The psychological burden of a questionable malignant diagnosis is considerable. Early use of contrast-enhanced sonography and, if necessary, puncture of unclear hepatic masses helps to shorten the difficult diagnostic process.

A rare disease: a single-center experience of cerebral alveolar echinococcosis in 12 operated patients.

In this study, we have evaluated 12 patients with cerebral alveolar echinococcosis (AE). All patients underwent surgery for cerebral AE. We aimed to demonstrate the relationship between the demographic properties of patients and surgical outcomes as well as surgical suggestions about surgical approaches. Patients were analyzed according to demographic properties, hepatic/ pulmonary AE lesion existence, symptoms, neurological and radiological examination, histopathological findings, and outcome after treatment. Preoperative diagnosis based on the history of the patient, neurological examination, serological tests, and radiology. When enhanced radiological imaging like MR-Tractography and intraoperative neuromonitoring is combined with precision surgical methods cerebral AE is treatable. Ten of twelve cerebral AE patients had favorable outcomes after surgery. AE of the brain is a rare but life-threatening parasitic disease. Wherever the primary focus is, surgery for cerebral involvement of AE is challenging but safe with appropriate surgical techniques and the help of radiological examination.

Application of hepatic lobe hyperplasia techniques in the treatment of advanced hepatic alveolar echinococcosis: a single-centre experience

BackgroundThis study was designed to investigate clinical efficiency and application indications of hepatic lobe hyperplasia techniques for advanced hepatic alveolar echinococcosis (AE) patients.MethodsA retrospective case series covering 19 advanced hepatic AE patients admitted to the First Affiliated Hospital of Xinjiang Medical University from September 2014 to December 2021 and undergoing hepatic lobe hyperplasia techniques due to insufficient remnant liver volume were analyzed. Changes of liver function, lesions volume, remnant liver volume, total liver volume before and after operation have been observed.ResultsAmong the patients, 15 underwent portal vein embolization (PVE). There was no statistical difference in total liver volume and lesions volume before and after PVE (P > 0.05). However, the remnant liver volume was significantly increased after PVE (P < 0.05). The median monthly increase rate in future liver remnant volume (FLRV) after PVE stood at 4.49% (IQR 3.55–7.06). Among the four patients undergoing two-stage hepatectomy (TSH), FLRV was larger than that before the first stage surgery, and the median monthly increase rate in FLRV after it stood at 3.34% (IQR 2.17–4.61). Despite no statistical difference in total bilirubin (TBil), albumin (Alb), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) in all patients with PVE, four patients who underwent TSH showed a decrease in ALT, AST and GGT. During the waiting process before the second stage operation, no serious complications occurred in all patients.ConclusionsFor patients suffering from advanced hepatic AE with insufficient FLRV, PVE and TSH are safe and feasible in promoting hepatic lobe hyperplasia.

Indoleamine 2,3-dioxygenase 1 signaling orchestrates immune tolerance in Echinococcus multilocularis-infected mice.

The cestode Echinococcus multilocularis larva infection causes lethal zoonotic alveolar echinococcosis (AE), a disease posing a great threat to the public health worldwide. This persistent hepatic tumor-like disease in AE patients has been largely attributed to aberrant T cell responses, of which Th1 responses are impeded, whilst Th2 and regulatory T cell responses are elevated, creating an immune tolerogenic microenvironment in the liver. However, the immune tolerance mechanisms are not fully understood. Dendritic cells (DCs) are key cellular components in facilitating immune tolerance in chronic diseases, including AE. Here, we demonstrate that indoleamine 2,3-dioxygenase 1-deficient (IDO1-/-) mice display less severe AE as compared to wild-type (WT) mice during the infection. Mechanistically, IDO1 prevents optimal T cells responses by programming DCs into a tolerogenic state. Specifically, IDO1 prevents the maturation and migration potential of DCs, as shown by the significantly enhanced expression of the antigen-presenting molecule (MHC II), costimulatory molecules (CD80 and CD86), and chemokine receptors (CXCR4 and CCR7) in infected IDO1-/- mice as compared to infected wild-type mice. More importantly, the tolerogenic phenotype of DCs is partly reverted in IDO1-/- mice, as indicated by enhanced activation, proliferation, and differentiation of both CD4+ and CD8+ - T cells upon infection with Echinococcus multilocularis, in comparison with WT mice. Interestingly, in absence of IDO1, CD4+ T cells are prone to differentiate to effector memory cells (CD44+CD62L-); in contrast, CD8+ T cells are highly biased to the central memory phenotype (CD44+CD62L+). Overall, these data are the first to demonstrate the essential role of IDO1 signaling in inducing immunosuppression in mice infected with Echinococcus multilocularis.