Alveolar Echinococcosis Research Articles

ХАРАКТЕРИСТИКА ИЗМЕНЧИВОСТИ ПАРАЗИТАРНЫХ СИСТЕМ ЭХИНОКОККОЗА И МНОГОКАМЕРНОГО ЭХИНОКОККОЗА ЗА МНОГОЛЕТНИЙ ПЕРИОД В КЫРГЫЗСКОЙ РЕСПУБЛИКЕ

Recently, the epidemic situation for echinococcosis in the Kyrgyz Republic (KR) is quite complicated. For the period from 1990 to 2019, according to the results of a retrospective analysis, in the Kyrgyz Republic – the highest prevalence of the population was recorded in 2014 and amounted to 20,20/0000. The lowest prevalence was in 1990 and the indicator was 5,20/0000. There is a tendency towards an increase in the incidence of echinococcosis of the entire population of the Kyrgyz Republic. The average annual growth rate was 3.5%. The mechanisms of cross-infection of a large biodiversity of intermediate hosts in agricultural and natural ecosystems are realized due to fertile strains of E. granulosus, and are mediated through a circle of definitive hosts. Echinococcosis is a complex parasitic system, the structural components of which are cestodes of the genus Echinococcus at different stages of development, as well as animals and humans, which are the hosts of various stages of the parasite’s life cycle. The population of parasites is an integrating link of the parasitic system formed by a specific population of the parasite and the populations of all hosts that support its existence. The parasitic system is based on the interaction between the populations of the parasite and the hosts, developed in the course of evolution. Key words: cystic echinococcosis, alveolar echinococcosis, parasitic system, characteristics of variability, focus, morbidity

Genome-wide profiling of the expression of serum derived exosomal circRNAs in patients with hepatic alveolar echinococcosis.

The patients with hepatic alveolar echinococcosis is poorly detected due to invasive and slow growth. Thus, early diagnosis of hepatic alveolar echinococcosis is so important for patients. Circular RNAs are crucial types of the non-coding RNA. Recent studies have provided serum-derived exosomal circRNAs as potential biomarkers for detection of various diseases. The clinical importance of exosomal circRNAs in hepatic alveolar echinococcosis have never been explored before. Here, we investigated the serum-derived exosomal circRNAs in the diagnosis of hepatic alveolar echinococcosis. Firstly, High-throughput Sequencing was performed using 9 hepatic alveolar echinococcosis and 9 control samples to detect hepatic alveolar echinococcosis related circRNAs. Afterwards, bioinformatic analyzes were performed to identify differentially expressed circRNAs and pathway analyzes were performed. Finally, validation of the determined circRNAs was performed using RT-PCR. The sequencing data indicated that 59 differentially expressed circRNAs; 31 up-regulated and 28 down-regulated circRNA in hepatic alveolar echinococcosis patients. The top 5 up-regulated and down-regulated circRNAs were selected for validation by RT-qPCR assay. As a result of the verification, circRNAs that were significantly up- and down-regulated showed an expression profile consistent with the results obtained. Importantly, our findings suggested that identified exosomal circRNAs could be a potential biomarker for the detection of hepatic alveolar echinococcosis serum and may help to understand the pathogenesis of hepatic alveolar echinococcosis.

Optimization of supercritical-CO2 extraction and pharmacokinetics in SD rats of alkaloids form Sophora moorcroftiana seed

The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box–Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatography coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 μg. The linear range of UPLC-HR-ESI-MS is 0.78–200.00 ng/ml, R2 > 0.99, and the sample recovery is 99–113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clinical applications.

Echinococcosis: a Challenge for Liver Sonography.

The sonographic findings in alveolar echinococcosis (AE) and cystic echinococcosis (CE) are complex and can pose significant differential diagnostic problems. They may present like complicated cysts or malignant tumors in the liver. We will discuss the diagnostic difficulties and pitfalls of these two diseases based on case histories.

Preliminary study on differentially expressed proteins in a mouse model of secondary alveolar echinococcosis based on data independent acquisition proteomics

To identify the differentially expressed proteins in different liver tissues in the mouse model of alveolar echinococcosis using high-resolution mass spectrometry with data independent acquisition (DIA), and to identify the key proteins contributing to the pathogenesis of alveolar echinococcosis. Protoscoleces were isolated from Microtus fuscus with alveolar echinococcosis and the experimental model of alveolar echinococcosis was established in female Kunming mice aged 6 to 8 weeks by infection with Echinococcus multilocularis protoscoleces. Mice were divided into the experimental and control groups, and animals in the experimental group was injected with approximately 3 000 protoscoleces, while mice in the control group were injected with the same volume of physiological saline. Mouse liver specimens were sampled from both groups one year post-infection and subjected to pathological examinations. In addition, the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the experimental group and the normal liver specimens (the normal group) were sampled from mice in the control group for DIA proteomics analysis, and the differentially expressed proteins were subjected to bioinformatics analysis. A total of 1 020 differentially expressed proteins were identified between the lesion group and the normal group, including 671 up-regulated proteins and 349 down-regulated proteins, and 495 differentially expressed proteins were identified between the peri-lesion group and the normal group, including 327 up-regulated proteins and 168 down-regulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these differentially expressed proteins were involved in peroxisome, peroxisome proliferator-activated receptor (PPAR) and fatty acid degradation pathways, and the peroxisome and PPAR signaling pathways were found to correlate with liver injury. Several differentially expressed proteins that may contribute to the pathogenesis of alveolar echinococcosis were identified in these two pathways, including fatty acid binding protein 1 (Fabp1), Acyl-CoA synthetase long chain family member 1 (Acsl1), Acyl-CoA oxidase 1 (Acox1), Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and Acetyl-Coenzyme A acyltransferase 1B (Acaa1b), which were down-regulated in mice in the experimental group. A large number of differentially expressed proteins are identified in the liver of the mouse model of alveolar echinococcosis, and Fabp1, Acsl1, Acox1, Ehhadh and Acaa1b may contribute to the pathogenesis of alveolar echinococcosis.

Imaging Aspects of Hepatic Alveolar Echinococcosis: Retrospective Findings of a Surgical Center in Turkey.

Radiologists should be aware of the findings of alveolar echinococcosis (AE) due to the diagnostic and management value of imaging. We are attempting to define the most common diagnostic imaging findings of liver AE, along with the prevalence and distribution of those findings. The patients’ US, CT, and MRI images were reviewed retrospectively. CT images were acquired with and without the administration of contrast medium. The MRI protocol includes T2-weighted images (WI), diffusion (WI), apparent diffusion coefficient (ADC) maps, and pre- and post-contrast T1WIs. The current study included 61 patients. The mean age of the population was 58.2 ± 9.6 years According to Kratzer’s categorization (US), 139 lesions (73.1%) were categorized as hailstorm. According to Graeter’s classification (CT), 139 (73.1%) lesions were type 1-diffuse infiltrating. The most frequent types were Kodama type 2 and 3 lesions (MRI) (42.6% and 48.7%, accordingly). P2N0M0 was the most frequent subtype. The current study defines the major, characteristic imaging findings of liver AE using US, CT, and MRI. Since US, CT, and MRI have all been utilized to diagnose AE, we believe that a multi-modality classification system is needed. The study’s findings may aid radiologists in accurately and timely diagnosing liver AE.

Evaluation of Eosinophilic Cationic Protein as a Marker of Alveolar and Cystic Echinococcosis.

Echinococcosis is a neglected zoonotic disease and a worldwide public health problem caused by infection with the larval stages of taeniid cestodes of the genus Echinococcus. In vitro studies have demonstrated a protoscolecidal effect of eosinophilic cationic protein (ECP), a granule protein of eosinophilic granulocytes, against E. granulosus. Therefore, the main objective of this study was to evaluate ECP as a biomarker in the treatment of alveolar echinococcosis (AE) and cystic echinococcosis (CE). Data were collected retrospectively from the Vienna Echinococcosis Cohort over 7 years until December 2020. Altogether, 32 patients (16 AE and 16 CE) were included. In the selected patients, serum ECP values were compared before and after the beginning of an operative and/or benzimidazole (BMZ) therapy. Mean ECP serum levels before intervention were significantly (p < 0.05) elevated at 34.0 ± 22.9 μg/L in AE patients and at 38.6 ± 19.9 μg/L in CE patients compared to the control group. After the intervention, mean ECP levels decreased significantly (p < 0.05) to 20.4 ± 14.6 μg/L in AE patients and to 22.4 ± 8.3 μg/L in CE patients. Furthermore, ECP showed a significant (p < 0.05) correlation of k = 0.56 with PET–CTI. Based on the significant decrease after operative and/or BMZ treatment and the correlation with clinical markers such as PET–CTI, it is recommended to investigate ECP more intensively as a marker of AE and CE in prospective studies with larger cohorts.

Evaluation of Serological Markers in Alveolar Echinococcosis Emphasizing the Correlation of PET-CTI Tracer Uptake with RecEm18 and Echinococcus-Specific IgG.

Human alveolar echinococcosis (AE), which is caused by the cestode Echinococcus (E.) multilocularis, is an epidemiologically relevant issue in modern medicine and still poses a diagnostic and therapeutic challenge. Since diagnosis mainly relies on imaging procedures and serological testing, we retrospectively and comparatively analyzed the performance of an Echinococcus IgG screening ELISA, whole serum IgE, and two specific confirmatory ELISA platforms using the defined E. multilocularis antigens Em2-Em18 (Em2+) and recombinant Em18 (recEm18). With special emphasis on the clinical usefulness of recEm18, we correlated the laboratory results with clinical characteristics and imaging findings in a large and well-characterized cohort of N = 124 AE patients, who were followed over several years after either surgical plus subsequent pharmacological treatment or pharmacotherapy alone. All patients had routinely received PET-CTI every two years. Our data reveal strong correlations for both Echinococcus IgG and recEm18 with tracer uptake in PET-CTI and parasitic lesion size and number, suggesting additional clinical usefulness of recEm18 for certain constellations only, while IgG and Em2+ still appear reasonable and sensitive screening methods for initial diagnosis of AE. With this study, we aim to contribute to further optimizing medical care of AE patients. For instance, it might be reasonable to consider the replacement of some PET-CTI follow-ups by imaging procedures with less radiation exposure or serological means alone. Further studies that clarify the correlation of serological markers with ultrasound criteria might be particularly useful, and further retrospective as well as prospective investigations are justified in this context.

Effectiveness and safety of ultrasound-guided percutaneous microwave ablation for hepatic alveolar echinococcosis

BackgroundMicrowave ablation (MWA) is a popular therapy for liver malignant tumor in recent years. Few studies have been conducted on its use in the treatment of hepatic alveolar echinococcosis (HAE). The study aims to evaluate the efficacy and safety of MWA in the treatment of HAE.MethodsThis study analyzed the data of 45 patients (mean age, 38 ± 2 years; 24 males) diagnosed with HAE and underwent MWA treatment between June 2014 to December 2019. The patients after MWA were examined by CT or MRI [follow-up: 32 months (IQR 23–48.5)] to determine whether the lesions were relapsed and to evaluate the therapeutic effect of MWA. The safety of MWA was evaluated by monitoring postoperative complications. Clinical data, such as patient demographics, imaging features of the lesions, relevant findings of laboratory tests before and after ablation, and information related to ablation, were collected and analyzed. Paired-sample t tests and paired-sample Wilcoxon signed-rank tests were used to compare relevant laboratory indicators before and after MWA.ResultsMWA was applied to 57 HAE lesions in 45 patients. The median size of lesions was 3.42 cm (IQR2.85–4.41). The rate of complete ablation was 100% (57/57). The median follow-up time was 32 months (IQR 23–48.5). The recurrence rate was 13% (6/45), and the median time of recurrence was 22 months. The rate of minor complications was 11.1% (5/45), and there were no major complications and deaths. Compared to preoperative, ALB, RBC, HBG, and PLT were decreased (p < 0.001); ALT, TB, DB, and WBC were increased (p < 0.001); and no statistically difference in PT, APTT, and INR (p > 0.05).ConclusionsMWA might be a safe and effective way to cure HAE. Meanwhile, it provides a new option and a new way of thinking about treatment for patients with HAE.

Comparison of the Efficacy of Anatomic and Non-anatomic Hepatectomy for Hepatic Alveolar Echinococcosis: Clinical Experience of 240 Cases in a Single Center

BackgroundHepatic alveolar echinococcosis (AE) is a zoonotic parasitic disease. There are more than 16,000 new cases each year, approximately 60 million people are threatened, and the annual direct economic loss is RMB 3 billion. The prevalence of AE in some areas of the Qinghai–Tibet Plateau is as high as 6.0%. Radical resection, including anatomic and non-anatomic hepatectomy, for advanced AE can significantly prolong the survival time of patients. However, there is no literature compared the efficacy of anatomic and non-anatomic hepatectomy. Therefore, by comparing various clinical evaluation indices between anatomic and non-anatomic hepatectomy, this study explored the short-term and long-term efficacy of these two surgical methods for AE.MethodsThe clinical data of patients with AE who underwent radical hepatectomy at Qinghai Provincial People's Hospital from January 2015 to January 2021 were retrospectively analyzed. The patients were divided into two groups by surgical method, that were, non-anatomic hepatectomy group and anatomic hepatectomy group. We compared these two groups focusing on basic preoperative data, such as age, sex, lesion size, and liver function parameters; main intraoperative evaluation indices, such as operation time, intraoperative porta hepatis occlusion time, intraoperative blood loss, and blood transfusion; and postoperative recovery evaluation indicators, such as postoperative liver function, incidence of surgical complications, and AE recurrence.ResultsA total of 240 patients were enrolled in this study, including 123 in anatomic hepatectomy group and 117 in non-anatomic hepatectomy group. There were no significant differences (P > 0.05) between baseline characteristics. Anatomic hepatectomy group was advantageous than non-anatomic hepatectomy group regarding intraoperative blood loss (P < 0.001), blood transfusion (P < 0.001), and porta hepatis occlusion time (P < 0.001). There were statistically significant differences in postoperative liver function (aspartate aminotransferase: P < 0.001; alanine aminotransferase: P < 0.001), surgical complications (P < 0.001), and AE recurrence rate (P = 0.003). The median survival of patients in the anatomic hepatectomy group was 66 months, compared to 65 months in the non-anatomic hepatectomy group (χ2 = 4.662, P = 0.031).ConclusionsAnatomic hepatectomy was not only safe for AE but also showed better short-term and long-term superiority than non-anatomic hepatectomy.

Echinococcus multilocularis specific antibody, systemic cytokine, and chemokine levels, as well as antigen-specific cellular responses in patients with progressive, stable, and cured alveolar echinococcosis: A 10-year follow-up.

BackgroundThe infestation with Echinococcus multilocularis larvae may persist in humans for up to decades without evident clinical symptoms. Longitudinal investigations are needed to understand the dynamic immunological processes in alveolar echinococcosis (AE) patients associated with an active and progressive, a stable or a regressive course of disease.Methodology/Principal findingsThis study evaluated the E. multilocularis specific antibody responses, systemic cytokine, and chemokine serum levels over a 10-year follow-up period, as well as cellular responsiveness in AE patients. Our results demonstrate a rapid decrease in antibodies against E. multilocularis specific antigen Em2+. Especially in cured patients, these antibodies remained negative, making them a significant predictor for cured AE. E. multilocularis specific IgG4, and indirect hemagglutination IHA decreased later in time, after around 5 years. While total IgE did not show significant dynamics over the course of disease, E. multilocularis specific IgE decreased after one to two years, and increasing levels were a significant predictor of progressive disease. There was no significant change in systemic IL-8, IL-9, CCL18 or CCL20 serum levels over time. Univariate analysis across groups indicated lower IL-8 levels in cured patients; however, this result could not be confirmed by multivariate analysis. Levels of CCL17 decreased during treatment, especially in cured patients, and thus might serve as a predictive or risk factor for progressive disease. Levels of IL-10 and CCL13 decreased during disease, especially after five and ten years of intervention. The E. multilocularis antigen (EmAg) inducible cellular productions of MCP1(CCL13), TARC(CCL17) and PARC(CCL18) were lowest in patients with cured AE and infection-free controls, while the EmAg inducible cellular production of IFN-γ increased after cure. Significant positive cytokine and chemokine correlations were observed in AE patients for IL-9, IL-10, CCL13(MCP-4), CCL17(TARC) and CCL20(LARC)(for all p<0.001). E. multilocularis specific IgG4 response correlated positively with TARC (p<0.001). Both markers enhanced over time in progressive disease and decreased after cure. The levels of IL-8, IL-10, MCP4 and LARC enhanced with AE regression.Conclusions/SignificanceRepeated biomarker surveys are advisable to evaluate progression or regression of disease during longitudinal follow-up and such analyses can support imaging techniques and improve staging of AE patients.

Echinococcus granulosus Protoscolex DM9 Protein Shows High Potential for Serodiagnosis of Alveolar Echinococcosis.

Alveolar echinococcosis (AE) caused by infection with E. multilocularis metacestode, represents one of the most fatal helminthic diseases. AE is principally manifested with infiltrative, proliferating hepatic mass, resembling primary hepatocellular carcinoma. Sometimes metastatic lesions are found in nearby or remote tissue. AE diagnosis largely depends on imaging studies, but atypical findings of imaging features frequently require differential diagnosis from other hepatic lesions. Serological tests may provide further evidence, while obtaining reliable AE materials is not easy. In this study, alternative antigens, specific to AE were identified by analyzing E. granulosus protoscolex proteins. An immunoblot analysis of E. granulosus protoscolex showed that a group of low-molecular-weight proteins in the range from 14 kDa to 16 kDa exhibited a sensitive and specific immune response to AE patient sera. Partial purification and proteomic analysis indicated that this protein group contained myosin, tubulin polymerization promoting protein, fatty-acid binding protein, uncharacterized DM9, heat shock protein 90 cochaperone tebp P-23, and antigen S. When the serological applicability of recombinant forms of these proteins was assessed using enzyme-linked immunosorbent assay, DM9 protein (rEgDM9) showed 90.1% sensitivity (73/81 sera tested) and 94.5% specificity (172/181 sera tested), respectively. rEgDM9 showed weak cross-reactions with patient sera from the transitional and chronic stages of cystic echinococcosis (3 to 5 stages). rEgDM9 would serve as a useful alternative antigen for serodiagnosis of both early- and advanced-stage AE cases.

An Excretory Protein of Echinococcus multilocularis Inhibits Complement Classical Pathway Activation.

IntroductionAlveolar echinococcosis is a lethal zoonosis caused by Echinococcus multilocularis (E.m) larvae. The mechanism by which E.m evades host immune attacks and ensures long-term survival remains unexplained. The complement system is a cascade of sequentially activated complement proteins that results in opsonization-related phagocytosis or membrane lysis of invading organisms. Excretory/secretory proteins (ESPs) of parasites are the main antigens that induce the immune response and play important roles in the long-term survival.MethodsWe investigated the possibility that E.m inhibits complement activation through ESPs and examined the potential related mechanism. A haemolysis assay was used to determine if and how in vitro culture medium of E.m containing ESPs can inhibit complement activation. Potential ESPs were annotated using bioinformatics methods, and one ESP was subsequently expressed as a recombinant protein with a eukaryotic expression system. The ability of this protein to inhibit complement activation was also tested by haemolysis assay.ResultsThese assays showed that in vitro culture medium of E.m inhibited activation of the complement classical pathway. EmuJ_000439500 encodes a protein containing seven Sushi domains, which was the only potential E.m-derived complement inhibitor (Em-CI, UniProt: A0A068Y4F2) annotated among the 653 ESPs. Recombinant Em-CI also displayed the ability to inhibit activation of the complement classical pathway.DiscussionThe discovery of Em-CI sheds light on the mechanism by which E.m escapes killing by the complement system and provides potential targets for immunotherapy for parasitic diseases.

Evaluation of a structured treatment discontinuation in patients with inoperable alveolar echinococcosis on long-term benzimidazole therapy: A retrospective cohort study

ObjectivesAlveolar echinococcosis (AE) is an orphan zoonosis of increasing concern in endemic areas, including Europe. It frequently presents in an advanced, inoperable stage, that requires life-long parasitostatic benzimidazole therapy. In some patients, long-term therapy leads to negative anti-Em18 antibody ELISA and PET. It is disputed, whether these patients are truly cured and treatment can be safely discontinued. Our aim was to retrospectively assess long-term outcome of 34 patients with inoperable AE who participated in a previous study to determine feasibility of benzimidazole treatment cessation.MethodsRetrospective analysis of medical charts was undertaken in all 34 AE patients who participated in our previous study. Of particular interest were AE recurrence or other reasons for re-treatment in patients who stopped benzimidazole therapy and whether baseline clinical and laboratory parameters help identify of patients that might qualifiy for treatment cessation. Additionally, volumetric measurement of AE lesions on contrast-enhanced cross-sectional imaging was performed at baseline and last follow-up in order to quantify treatment response.Results12 of 34 patients stopped benzimidazole therapy for a median of 131 months. 11 of these patients showed stable or regressive AE lesions as determined by volumetric measurement. One patient developed progressive lesions with persistently negative anti-Em18 antibody ELISA but slight FDG-uptake in repeated PET imaging. At baseline, patients who met criteria for treatment cessation demonstrated higher lymphocyte count and lower total IgE.ConclusionTreatment cessation is feasible in inoperable AE patients, who demonstrate negative anti-Em18 antibody ELISA and PET on follow-up. Close monitoring including sectional imaging is strongly advised.

Transcriptional effects of electroporation on Echinococcus multilocularis primary cell culture.

Echinococcus multilocularis is the etiological agent of alveolar echinococcosis (AE), a serious parasitic disease in the Northern Hemisphere. The E. multilocularis primary cell cultivation system, together with E. multilocularis genome data and a range of pioneering molecular-based tools have advanced the research on this and other cestodes. RNA interference (RNAi) and microRNA knock-down have recently contributed to the study of the cellular and molecular basis of tapeworm development and host-parasite interaction. These, as well as other techniques, normally involve an electroporation step for the delivery of RNA, DNA, peptides, and small molecules into cells. Using transcriptome data and bioinformatic analyses, we herein report a genome-wide comparison between primary cells of E. multilocularis and primary cells under electroporated conditions after 48h of culture. We observed that ~ 15% of genes showed a significant variation in expression level, including highly upregulated genes in electroporated cells, putatively involved in detoxification and membrane remodeling. Furthermore, we found genes related to carbohydrate metabolism, proteolysis, calcium ion binding and microtubule processing significantly altered, which could explain the cellular dispersion and the reduced formation of cellular aggregates observed during the first 48h after electroporation.

Stage-Oriented CT Classification and Intermodal Evolution Model inHepatic Alveolar Echinococcosis.

BackgroundAlveolar echinococcosis (AE) is one of the most dangerous human parasitoses. The main site of disease manifestation is the liver (about 98 %). The Echinococcus Multilocularis Ulm Classification for Computed Tomography (EMUC-CT), presented in 2016, was the first compilation of CT morphological criteria of hepatic AE. Studies based on EMUC-CT made it possible to draw conclusions about the development of the lesions in the course of disease beyond purely diagnostic typing. Among the most important findings of these precursor studies was that EMUC-CT type IV presented as an initial lesion, whereas EMUC-CT type III lesions were mostly associated with an advanced disease constellation. An intermodal view of image morphological criteria provides further multi-layered indications for lesion evolution.MethodWith the “Alveolar Echinococcosis Ulm Classification” (AEUC), a revision of the previous EMUC-CT was carried out with stage-oriented reorganization of the primary morphologies. Furthermore, an intermodal classification scheme for the evolution of hepatic AE lesions based on AEUC, MRI Kodama classification, and aspects of ultrasound could be outlined.ResultsThe first stage-oriented CT classification of hepatic AE “AEUC” is based with respect to its lesion characterization on the separate consideration of two classification pillars, the five “primary morphologies”, AEUC I–V (AEUC II–IV with subcriteria) and the five “patterns of calcification”. In addition, an intermodal classification scheme presents five stages of lesion evolution: “initial stage”, “progressive stage”, “advanced stage”, “transitional stage” and “regressive stage”.ConclusionThe imaging modalities differ with respect to their visualization of lesion criteria. This underlines the need for unimodal classification systems. Staging of an AE lesion can be done more accurately by evaluating different modalities.Key Points:The AEUC provides a stage-oriented CT classification for hepatic AE.Aspects of different modalities allow a more multi-layered view of lesion evolution.More accurate staging can be achieved by combining different modalities.Citation FormatGraeter T, Schmidberger J. Stage-Oriented CT Classification and Intermodal Evolution Model in Hepatic Alveolar Echinococcosis. Fortschr Röntgenstr 2022; 194: 532 – 544

Autocrine osteopontin is involved in maintaining the growth and metastasis of Echinococcus multilocularis

Alveolar echinococcosis is a zoonotic disease that seriously endangers human health. This study aims to investigate the effects of osteopontin on the growth and intra- or extra-hepatic metastasis of Echinococcus multilocularis. Mice were randomly divided into untreated (control group, n = 25), PBS (n = 25), Lv3-NC (n = 25), and Lv-OPN-734 (n = 25) groups. Knockdown OPN by injecting lentivirus through the intraperitoneal portal vein, the metastatic lesions infected with Echinococcus multilocularis and adjacent liver tissues were observed, and the expression of osteopontin and epidermal growth factor receptor pathway-related molecules were studied. Gross observation of specimens suggested that there was no extra- hepatic metastasis, and mild intrahepatic invasion was observed in the Lv-OPN-734 group after 4 months of infection, and lung metastasis occurred in the Lv3-NC group. Western-blot and immunohistochemical staining results showed that the protein expression of OPN, phosphorylation of epidermal growth factor receptor and downstream molecules of the pathway decreased significantly after osteopontin knockdown, whereas the levels of non-phosphorylated proteins did not change significantly. In human tissues, through western-blot and immunohistochemical staining we found that compared with the control group, the expression of OPN in the liver tissues infected with Echinococcus multilocularis were higher than that in the control group. These findings indicate that osteopontin is involved in maintaining the growth and metastasis of Echinococcus multilocularis, suggesting that osteopontin may be a potential target for the treatment of alveolar echinococcosis.

Geographic distribution and prevalence of human echinococcosis at the township level in the Tibet Autonomous Region

BackgroundEchinococcosis, a zoonotic parasitic disease, is caused by larval stages of cestodes in the Echinococcus genus. Echinococcosis is highly prevalent in ten provinces/autonomous regions of western and northern China. In 2016, an epidemiological survey of Tibet Autonomous Region (TAR) revealed that the prevalence of human echinococcosis was 1.66%, which was much higher than the average prevalence in China (0.24%). Therefore, to improve on the current prevention and control measures, it is important to understand the prevalence and spatial distribution characteristics of human echinococcosis at the township level in TAR.MethodsData for echinococcosis cases in 2018 were obtained from the annual report system of echinococcosis of Tibet Center for Disease Control and Prevention. Diagnosis had been performed via B-ultrasonography. The epidemic status of echinococcosis in all townships in TAR was classified according to the relevant standards of population prevalence indices as defined in the national technical plan for echinococcosis control. Spatial scan statistics were performed to establish the geographical townships that were most at risk of echinococcosis.ResultsIn 2018, a total of 16,009 echinococcosis cases, whose prevalence was 0.53%, were recorded in 74 endemic counties in TAR. Based on the order of the epidemic degree, all the 692 townships were classified from high to low degrees. Among them, 127 townships had prevalence rates ≥ 1%. The high prevalence of human echinococcosis in TAR, which is associated with a wide geographic distribution, is a medical concern. Approximately 94.65% of the villages and towns reported echinococcosis cases. According to spatial distribution analysis, the prevalence of human echinococcosis was found to be clustered, with the specific clustering areas being identified. The cystic echinococcosis primary cluster covered 88 townships, while that of alveolar echinococcosis’s covered 38 townships.ConclusionsThis study shows spatial distributions of echinococcosis with different epidemic degrees in 692 townships of TAR and high-risk cluster areas at the township level. Our findings indicate that strengthening the echinococcosis prevention and control strategies in TAR should directed at townships with a high prevalence and high-risk clustering areas.Graphical

Study on the Effect of Quasi-Radical Lesion Resection on the Quality of Life of Patients With Advanced Hepatic Alveolar Echinococcosis

ObjectiveTo retrospectively analyze the effects of radical lesion resection and quasi radical lesion resection on the quality of life of patients with advanced hepatic alveolar echinococcosis.MethodsThrough the existing HIS system of Qinghai Provincial People's Hospital, 104 patients with hepatic alveolar echinococcosis who underwent surgical treatment in our hospital from January 2012 to December 2017 and completed the quality of life questionnaire were selected as the research objects. The above cases were divided into radical group (n = 51) and quasi-radical group (n = 53) according to different surgical methods (degree of radical cure). The quality of life of patients with hydatidosis was measured by interview or telephone follow-up. The preoperative indexes, intraoperative conditions and postoperative recovery indicators of the two groups were observed, such as Child-Puhg grade, PNM classification, scope of hepatectomy, intraoperative bleeding, Clavien grade, incidence of complications, 5-year recurrence rate and total score of quality of life and so on.ResultsThere was no significant difference between the two groups in general data such as age, gender, hydatid size, Child-Puhg grade and preoperative liver function (P > 0.05). However, there was a statistically significant difference in PNM classification between the two groups (P < 0.05). There were significant differences in intraoperative bleeding, postoperative liver function recovery, Clavien grade of complication severity and 5-year recurrence rate between the two groups (P < 0.05). There was no significant difference in postoperative quality of life between the two groups (P > 0.05).ConclusionFor patients with advanced hepatic alveolar echinococcosis whose objective cannot be achieved by conventional hepatectomy, quasi-radical resection of the lesion can not only reduce the risk and difficulty of surgery, but also the quality of life of the patients may be as good as that of radical resection.

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection.

BackgroundEchinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice.MethodsE. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes.ResultsE. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels.Conclusions and significanceAE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.