Metabolic mechanism and pharmacological study of albendazole in secondary hepatic alveolar echinococcosis (HAE) model rats.

Albendazole (ABZ) is the primary treatment for alveolar echinococcosis (AE); however, its limited solubility impacts oral bioavailability, affecting therapeutic outcomes. In this study, various ABZ-solubilizing formulations, including albendazole crystal dispersion system (ABZ-CSD), albendazole hydrochloride-hydroxypropyl methylcellulose phthalate composite (TABZ-HCl-H), and albendazole hydroxyethyl sulfonate-hydroxypropyl methylcellulose phthalate composite (TABZ-HES-H), were developed and evaluated. Physicochemical properties as well as liver enzyme activity were analyzed and their pharmacodynamics in an anti-secondary hepatic alveolar echinococcosis (HAE) rat model were investigated. The formulations demonstrated improved solubility, exhibiting enhanced inhibitory effects on microcysts in HAE model rats compared to albendazole tablets. However, altered hepatic drug-metabolizing enzymes in HAE model rats led to increased ABZ levels and reduced ABZ-SO production, potentially elevating drug toxicity. These findings emphasize the importance of dose adjustments in patient administration, considering the impact of alveolar echinococcosis on rat hepatic drug metabolism.

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.

Single-center experience of Ex vivo liver resection and autotransplantation for complex hepatic alveolar echinoccosis.

Objective: To summarize the single-centre experience of Ex vivo Liver Resection and Autotransplantation (ELRA) to treat end-stage hepatic alveolar echinococcosis (HAE). Methods: Retrospective analysis of clinical data and follow-up data of 13 patients admitted to the Affiliated Hospital of Qinghai University from January 2015 to December 1, 2020, with the Ex vivo Liver Resection and Autotransplantation for hepatic alveolar echinococcosis. Result: 13 patients underwent successful total/ semi-ex-vivo liver resection combined with Ex vivo Liver Resection and Autotransplantation with no intra-operative deaths. the median standard liver volume was 1,118 ml (1,085-1,206.5 ml); the median residual liver volume was 634 ml (526.5-1,338 ml); The median weight of the autograft was 845.8 g (619.5-1,020.5 g), the median operation time was 14.5 h (11.5-16.15 h); the median anhepatic period time was 290 min (257-312.5 min). The median intraoperative blood loss was 1,900 ml (1,300-3,500 ml); the median number of erythrocyte suspensions entered was 7.5 u (6-9u). The median length of hospital stay was 32 days (24-40 days). Postoperative complications occurred in 9 patients during hospitalization,with 7 patients graded at grade III or higher by Clavien-Dindo; 4 patients died postoperatively. 1 patient had recurrent abdominal distension with massive thoracoabdominal fluid and coagulation dysfunction 8 months after surgery and was considered to have small liver syndrome. 1 patient developed HAE recurrence during the follow-up, which was considered intraoperative incisional implantation. Conclusion: ELRA is one of the most valuable therapeutic measures for the treatment of end-stage complicated hepatic alveolar echinococcosis. Precise preoperative assessment of liver function, individualized intraoperative duct reconstruction, and precise management of the postoperative disease can achieve better treatment results.

Advances in the pharmacological treatment of hepatic alveolar echinococcosis: From laboratory to clinic.

Hepatic alveolar echinococcosis (HAE) is a zoonotic parasitic disease caused by the larvae of Echinococcus multilocularis. Because of its characteristics of diffuse infiltration and growth similar to tumors, the disability rate and mortality rate are high among patients. Although surgery (including hepatectomy, liver transplantation, and autologous liver transplantation) is the first choice for the treatment of hepatic alveolar echinococcosis in clinic, drug treatment still plays an important and irreplaceable role in patients with end-stage echinococcosis, including patients with multiple organ metastasis, patients with inferior vena cava invasion, or patients with surgical contraindications, etc. However, Albendazole is the only recommended clinical drug which could exhibit a parasitostatic rather than a parasitocidal effect. Novel drugs are needed but few investment was made in the field because the rarity of the cases. Drug repurposing might be a solution. In this review, FDA-approved drugs that have a potential curative effect on hepatic alveolar echinococcosis in animal models are summarized. Further, nano drug delivery systems boosting the therapeutic effect on hepatic alveolar echinococcosis are also reviewed. Taken together, these might contribute to the development of novel strategy for advanced hepatic alveolar echinococcosis.

Alterations in the Gut Microbiota of Tibetan Patients With Echinococcosis.

There are two main types of echinococcosis, namely alveolar echinococcosis (AE) and cystic echinococcosis (CE). They are zoonotic parasitic diseases caused by the metacestodes of Echinococcus multilocularis and Echinococcus granulosus. In order to explore the gut microbiome composition of patients with echinococcosis, we analyzed fecal samples of seven patients with AE, six patients with CE, and 13 healthy individuals from the Qinghai-Tibetan Plateau, China. Using metagenomic next-generation sequencing, we identified fecal bacteria in the patients with AE and CE. The gut microbiota was analyzed by next-generation metagenomic sequencing (mNGS) to compare patients with either AE or CE against healthy individuals. We found there were some differences between them in abundant bacteria. Our results led to five findings: (1) Between patients with echinococcosis and healthy individuals, the differential bacteria were from four phyla: Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria. (2) Rothia mucilaginosa, Veillonella dispar, Veillonella atypica, Streptococcus parasanguinis, Streptococcus salivarius, and Alistipes finegoldii were abundant in the feces of patients with AE. (3) Bacteroides dorei, Parabacteroides distasonis, Escherichia sp_E4742, and Methanobrevibacter smithii were abundant in the feces of the patients with CE. (4) At the phylum and class level, compared to the AE group, the healthy group was characterized by higher numbers of Actinobacteria. (5) At the family level, Lachnospiraceae and Eubacteriaceae were more abundant in the feces of healthy individuals than in AE patients. The genera Coprococcus, Eubacterium, and Bilophia were more abundant in the healthy group, while the genus Rothia was more abundant in the AE group. The results of this study enrich our understanding of the gut microbiome composition of patients with AE and CE in the Qinghai-Tibetan Plateau.

Prediction and identification of epitopes in the Echinococcus multilocularis thrombospondin 3 antigen.

BACKGROUND: Alveolar echinococcosis is an epidemic disease caused by the parasitism of Echinococcus multilocularis (Em) larvae in the intermediate or final host. OBJECTIVE: To identify and analyze B-cell and T-cell (Th1, Th2, and Th17) epitopes of the Em antigen protein thrombospondin 3 (TSP3). METHODS: The amino acid sequence of TSP3 was obtained, and the secondary structural characteristics of TSP3 were predicted using bioinformatics software to further predict its potential T-cell and B-cell epitopes. The spleen lymphocytes of BALB/c mice, which were immunized with the TSP3 protein, were collected for co-culture with B-cell and T-cell antigen small peptides. The B-cell epitopes and T-cell epitope subtypes Th1, Th2, and Th17 were identified as having good immunogenicity. RESULTS: After identification, it was found that the predominant epitopes of B cells existing in TSP3 were T18-33, T45-55, and T110-122. Furthermore, the predominant epitopes of T cells existing in TSP3 were T33-42, T45-55, T80-90, and T110-122 in the T1 subtype, T45-55, T68-77, and T92-104 in the Th2 subtype, and T53-63 and T80-90 in the Th17 subtype. CONCLUSIONS: Six T-cell and eight B-cell dominant epitopes of the TSP3 antigen were revealed; these results may be applied in the development of a dominant epitope vaccine.

The Correlation Between Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio with Hepatic Echinococcosis.

OBJECTIVE: To explore the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with hepatic hydatid diseases. METHODS: The clinical data of 420 patients with hydatid disease who were treated in our hospital from October 2015 to October 2018 were collected from the database of our hospital. According to the postoperative pathological diagnosis, 200 patients were assigned into the alveolar echinococcosis (AE) group, and 220 patients were assigned into the cystic echinococcosis (CE) group. A total of 160 healthy examinees were enrolled as the control group. The main observation indexes included preoperative PLR and NLR. Pearson's correlation was used to analyze the correlation between PLR and NLR with clinical indicators in HE patients, and the receiver operator characteristic (ROC) curve was used to evaluate the clinical values of PLR and NLR in diagnosing different types of hydatid diseases. RESULTS: The results revealed that the expressions of PLR and NLR were significantly higher in the AE group than in the CE and control groups (P<0.05). The results of multiple linear regression analysis revealed that PLR was positively correlated with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase (P<0.05). NLR was correlated with albumin content (P<0.05). ROC curve analysis results revealed that the area under the curve (AUC) of PLR and NLR for AE was 0.800 and 0.700 respectively, and the AUC for CE was 0.78 and 0.75 respectively. CONCLUSION: The NLR and PLR of AE patients were higher than those of CE patients, and the high inflammation of CE patients may be correlated to the reproductive mode of Echinococcus multilocularis. PLR and NLR have certain diagnostic values for disease classification, but PLR has higher specificity when compared with NLR.

Nutritional status and screening tools to detect nutritional risk in hospitalized patients with hepatic echinococcosis.

BACKGROUND: Echinococcosis is a chronic consumptive liver disease. Little research has been carried out on the nutritional status of infected patients, though liver diseases are often associated with malnutrition. Our study investigated four different nutrition screening tools, to assess nutritional risks of hospitalized patients with echinococcosis. METHODS: Nutritional Risk Screening 2002 (NRS 2002), Short Form of Mini Nutritional Assessment (MNA-SF), Malnutrition Universal Screening Tool (MUST), and the Nutrition Risk Index (NRI) were used to assess 164 patients with alveolar echinococcosis (AE) and 232 with cystic echinococcosis (CE). Results were then compared with European Society for Clinical Nutrition and Metabolism (ESPEN) criteria for malnutrition diagnosis. RESULTS: According to ESPEN standards for malnutrition diagnosis, 29.2% of CE patients and 31.1% of AE patients were malnourished. The malnutrition risk rates for CE and AE patients were as follows: NRS 2002 - 40.3% and 30.7%; MUST - 51.5% and 50.9%; MNA-SF - 46.8% and 44.1%; and NRI - 51.1% and 67.4%. In patients with CE, MNA-SF and NRS 2002 results correlated well with ESPEN results (k = 0.515, 0.496). Area-under-the-curve (AUC) values of MNA-SF and NRS 2002 were 0.803 and 0.776, respectively. For patients with AE, NRS 2002 and MNA-SF results correlated well with ESPEN (k = 0.555, 0.493). AUC values of NRS 2002 and MNA-SF were 0.776 and 0.792, respectively. CONCLUSION: This study is the first to analyze hospitalized echinococcosis patients based on these nutritional screening tools. Our results suggest that NRS 2002 and MNA-SF are suitable tools for nutritional screening of inpatients with echinococcosis.

TITLE: État nutritionnel et outils de dépistage pour détecter le risque nutritionnel chez les patients hospitalisés atteints d'échinococcose hépatique. ABSTRACT: Contexte : L'échinococcose est une maladie hépatique consommatrice chronique. Il existe peu de recherches sur l'état nutritionnel des patients infectés, bien que les maladies du foie soient souvent associées à la malnutrition. Notre étude a examiné quatre différents outils de dépistage nutritionnel, pour évaluer les risques nutritionnels des patients hospitalisés atteints d'échinococcose. Méthodes : Les méthodes Nutritional Risk Screening 2002 (NRS 2002), Short Form of Mini Nutritional Assessment (MNA-SF), Malnutrition Universal Screening Tool (MUST) et Nutrition Risk Index (NRI) ont été utilisées pour évaluer 164 patients atteints d'échinococcose alvéolaire (EA) et 232 avec échinococcose kystique (EK). Les résultats ont ensuite été comparés aux critères de la Société européenne pour la nutrition clinique et le métabolisme (ESPEN) pour le diagnostic de la malnutrition. Résultats : Selon les normes ESPEN pour le diagnostic de la malnutrition, 29,2 % des patients avec EK et 31,1 % des patients avec EA étaient malnutris. Les taux de risque de malnutrition pour les patients EK et EA étaient, respectivement : NRS 2002 - 40,3 % et 30,7 % ; MUST - 51,5 % et 50,9 % ; MNA-SF - 46,8 % et 44,1 % ; NRI - 51,1 % et 67,4 %. Chez les patients atteints d'EK, les résultats de MNA-SF et NRS 2002 étaient bien corrélés aux résultats ESPEN (k = 0,515, 0,496), et les valeurs de l'aire sous la courbe (ASC) du MNA-SF et du NRS 2002 étaient respectivement de 0,803 et 0,776. Pour les patients atteints d'EA, les résultats NRS 2002 et MNA-SF étaient bien corrélés avec ESPEN (k = 0,555, 0,493), et les valeurs de l'ASC du NRS 2002 et du MNA-SF étaient respectivement de 0,776 et 0,792. Conclusion : Cette étude est la première à analyser les patients hospitalisés atteints d'échinococcose à partir de ces outils de dépistage nutritionnel. Nos résultats suggèrent que les méthodes NRS 2002 et MNA-SF sont des outils appropriés pour le dépistage nutritionnel des patients hospitalisés atteints d'échinococcose.

Nomogram Analysis and Internal Validation to Predict the Risk of Cystobiliary Communication in Patients Undergoing Hydatid Liver Cyst Surgery.

PURPOSE: Biliary leakage caused by cystobiliary communication (CBC) is a common clinical concern. This study sought to identify predictors of CBC in hepatic cystic echinococcosis (HCE) patients undergoing hydatid liver cyst surgery and establish nomograms to predict CBC. METHODS: A predictive model was established in a training cohort of 310 HCE patients diagnosed between January 2013 and May 2017. Upon revision of the records of clinical parameters and imaging features of these patients, the lasso regression model was used to optimize feature selection for the CBC risk model. Combined with feature selection, a CBC nomogram was developed with multivariable logistic regression. C-index and calibration plots were used to analyze and evaluate the discrimination and calibration. The net benefit and predictive accuracy of the nomogram were performed via decision curve analysis (DCA) and receiver operating characteristic (ROC) curve. An independent validation cohort of 132 patients recruited from June 2017 to May 2019 was used to evaluate the practicability of the nomogram. RESULTS: Predictors contained four features, namely alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), cyst size and cyst location. The C-index of the nomogram is 0.791 (95% CI, 0.736-0.845), while the C-index verified by bootstrap is 0.746, indicating high prediction accuracy. The area under the curve (AUC) of the CBC in training was 0.766. ROC curve analysis demonstrated high sensitivity and specificity. Decision curve analysis confirmed the CBC nomogram was clinically useful when the intervention was determined at the non-adherence possibility threshold of 8%. CONCLUSION: The nomogram developed using the ALP, GGT, cyst size and cyst location could be used to facilitate the CBC risk prediction in HCE patients.

Prediction and Identification of Epitopes in the Emy162 Antigen of Echinococcus multilocularis.

INTRODUCTION: Alveolar echinococcosis (AE) is a zoonotic disease caused by the parasitism of Echinococcus multilocularis larvae in the intermediate host or the final host. This study aims to identify and analyze the B-cell and T-cell (Th1, Th2 and Th17) epitopes of E. multilocularis antigen Emy162. METHODS: (1) The secondary structural characteristics of the Emy162 protein were predicted by bioinformatics software to further predict the potential T- and B-cell epitopes. (2) The dominant antigen epitopes were detected by ELISA through the reaction of patient serum with small B-cell antigen peptide and assessing the proliferation of splenic lymphocytes of mice immunized with Emy162. (3) The expression of cytokines in splenic lymphocytes of mice stimulated by small T-cell antigen peptides was detected by ELISA, ELISpot and flow cytometry to enable the identification of the T-cell epitopes. RESULTS: (1) The high-scored T-cell epitopes were located at positions E7-13, E36-41, E80-89, E87-96, E97-106 and E129-139, while B-cell epitopes were located at positions E7-13, E19-27, E28-36, E37-48, E78-83, E101-109, E112-121 and E129-139. (2) The three advanced antigen epitopes of Emy162 were E19-27, E112-121 and E129-139. (3) The four Th1 advanced antigen epitopes of Emy162 were E7-13, E36-41, E80-89 and E129-139. The three Th2 advanced antigen epitopes were E36-41, E87-96 and E97-106. The three Th17 advanced antigen epitopes were E36-41, E87-96 and E97-106. CONCLUSION: (1) The Emy162 protein has advanced antigenicity and numerous potential epitopes. Six T-cell and eight B-cell dominant epitopes were revealed using bioinformatics methods. (2) There are three dominant B-cell epitopes, four dominant Th1 epitopes, three dominant Th2 epitopes, and three dominant Th17 epitopes in the Emy162 antigen.

Relationship between platelet-based models and the prognosis of patients with malignant hepatic tumors.

Platelets (PLTs) are involved in tumor growth, metabolism and vascular activation. PLT-based models have been reported to have significant value on the recurrence of malignant hepatic tumors. The present study aimed to investigate the effect of PLT count and 18 PLT-based models on the prognosis of patients with malignant hepatic tumors. The clinical data from 189 patients with malignant hepatic tumors were retrospectively analyzed and used to calculate the scores of the 18 PLT-based models. Receiver operating characteristic curve was used to determine the suitable cut-off values of mortality and recurrence in patients with malignant hepatic tumors. The overall survival and cumulative recurrence rates of patients were calculated using Kaplan-Meier survival curves and the difference was analyzed using log-rank test. Multivariate analysis was performed to determine the independent risk factors of recurrence-free survival and overall survival. In the present study, 11 models were considered as predictors of mortality (P<0.05) and six models were considered as predictors of recurrence (P<0.05). The results from multivariate analysis demonstrated that vascular cancer embolus, uric acid >231 µmol/l, hemoglobin >144 g/l and the Lok index model >0.695 were considered as independent risk factors of mortality (P<0.05). Furthermore, vascular cancer embolus, PLT to lymphocyte ratio (PLR) >175 and fibrosis-4 (FIB-4) >4.82 were independent factors of recurrence (P<0.05). In addition, the results from this study indicated that the Lok-index could be considered as a predictor of the overall survival rate. In conclusion, the FIB-4 and PLR model may be valuable for predicting the recurrence-free rate of patients with malignant hepatic tumors.

Diagnosis and treatment of a case of hepatic mixed echinococcosis infection combined with distant organ metastasis.

Hydatidosis is a zoonotic parasitic disease caused by Echinococcus, which is highly prevalent in pastoral areas. In China, this disease is mainly caused by Echinococcus granulosus and Echinococcus multilocularis. Cystic echinococcosis, which is one of the most common types of echinococcosis, is described as swelling and growth of cystic lesions. Alveolar echinococcosis, which is less common, is invasive. Cases of mixed echinococcosis infection accompanied by extrahepatic organ metastasis are extremely rare. Treatment of these cases is complicated and the prognosis is extremely poor. We report a case of hepatic echinococcosis in a 40-year-old Tibetan man who was treated with the hepatic right tricuspidectomy + left hepatic duct jejunostomy (Roux-en-Y) surgical procedure. This procedure provides a reference for treatment of similar cases of echinococcosis. For patients with multiorgan metastasis, chemotherapy is the first choice. This should be followed by possible surgical treatment for life-threatening lesions of alveolar echinococcosis and subsequent chemotherapy. Individualized treatment accompanied by multidisciplinary treatment and damage control surgery could optimally benefit patients with advanced hepatic echinococcosis.

Primary splenic hydatidosis: a case report.

We herein report a case of primary splenic hydatidosis to provide data regarding the diagnosis, treatment, and epidemiological statistics of this disease. The patient was from a pastoral area and was diagnosed with primary splenic hydatidosis with chronic atrophic gastritis. The patient had no history of surgical treatment of hydatidosis. The diagnosis was mainly based on possible exposure to endemic areas, imaging findings, serological test results, and operative and pathological examination findings. Laparoscopic splenectomy was performed, and regular albendazole therapy was given after the operation. The patient was admitted to the hospital for gastrointestinal bleeding 3 months postoperatively, and she was successfully treated and discharged. No recurrence of hydatid foci has been observed since the follow-up.