Location and extent of cavernous transformation of the portal vein dictates different visceral side revascularization in Meso-Rex bypass.

BACKGROUND: As an emerging standard of care for portal vein cavernous transformation (PVCT), Meso-Rex bypass (MRB) has been complicated and variated. The study aim was to propose a new classification of PVCT to guide MRB operations. METHODS: Demographic data, the extent of extrahepatic PVCT, surgical methods for visceral side revascularization, intraoperative blood loss, operating time, changes in visceral venous pressure before and after MRB, postoperative complications and the condition of bypass vessels after MRB were extracted retrospectively from the medical records of 19 patients. RESULTS: The median age of the patients (13 males and 6 females) was 32.5 years, while two patients were underage. Causes of PVCT can be summarized as follows: thrombophilia such as dysfunction of antithrombin III or proteins C; secondary to abdominal surgeries; secondary to abdominal infection or traumatic intestinal obstruction, and unknown causes. Intraoperatively, the median operation time was 9.5 h (7-13 h), and the intraoperative blood loss was 300 mL (100-1,600 mL). Ten cases used autologous blood vessels while 10 used allogeneic blood vessels. The vascular anastomosis was divided into the following types according to the site and approach: Type (T) 1-PV pedicel type, T2-confluence type, T3-major visceral vascular type; and T4-collateral visceral vascular type. Furthermore, the visceral venous pressure before and after MRB dropped significantly from 36 cmH2O (28-44) to 24.5 cmH2O (15-31) (P < 0.01). Postoperatively, one patient had delayed wound healing, two developed biochemical pancreatic fistulae, one experienced lymphatic leakage, the former caused by heat damage of the pancreatic tissues, the latter by cutting lymphatic vessels in the mesentery or removing the local lymph nodes during the process of separating the superior mesenteric vein, and one was re-operated on for an intervening intestinal fistulae. Postoperative enhanced CT scans revealed a significant improvement in abdominal varix in the patients with patent bypass, and at the 1-year postoperative follow-up, enhanced CT scans of six patients showed that the long axis of the spleen was reduced by ≥ 2 cm. CONCLUSIONS: MRB can effectively reduce visceral venous pressure in patients with PVCT. It is feasible to determine the PVCT type according to the extent of involvement and to choose individualized visceral side revascularization performances.

NIR-II fluorescence microscopic bioimaging for intrahepatic angiography and the early detection of Echinococcus multilocularis microlesions.

Hepatic alveolar echinococcosis (HAE) is caused by the metacestode of Echinococcus multilocularis, which shows characteristics of malignant tumors with high mortality. However, traditional diagnostic imaging methods are still not sufficient for the recognition of HAE microlesions in the early stages. Near-infrared-II (900-1700 nm, NIR-II) fluorescence microscopic imaging (NIR-II-FMI) has shown great potential for biomedical detection. A novel type of negative target imaging method based on NIR-II-FMI with the assistance of indocyanine green (ICG) was explored. Then, NIR-II-FMI was applied to the early detection of HAE for the first time. The negative targeting NIR-II fluorescence imaging of HAE-infected mice at different stages with the assistance of ICG under 808 nm of laser irradiation was obtained. Especially, HAE microlesions at the early stage were detected clearly. Moreover, clear intrahepatic angiography was achieved under the same NIR-II-FMI system.

Differential Gene Expression Profiling in Alveolar Echinococcosis Identifies Potential Biomarkers Associated With Angiogenesis.

Background: Alveolar echinococcosis (AE) is a worldwide zoonosis caused by Echinococcus multilocularis. Alveolar echinococcosis is a severe chronic parasitic disease that exhibits a tumor-like growth, with the potential for invasion and distant metastasis; however, the molecular mechanism underlying this condition remains unclear. Methods: Transcriptome analyses were performed to detect differentially expressed genes (DEGs) in samples from patients with AE with invasion and distant metastasis. The results were further verified by immunohistochemistry. Results: A total of 1796 DEGs were identified, including 1742 upregulated and 54 downregulated DEGs. A subsequent functional analysis showed that the significant DEGs were involved in the angiogenesis process. Immunohistochemical analysis confirmed the reliability of the transcriptomic data. Conclusions: These results suggest that angiogenesis is a possible mechanism underlying the tumor-like biological behavior observed during E multilocularis infection. Genes related to this process may play important roles in AE invasion and distant metastasis.

Study on the characteristics of 18F-flurodeoxyglucose uptake in the microenvironment of hepatic alveolar echinococcosis / 中华肝胆外科杂志

Objective:To investigate characteristics of the 18F-flurodeoxyglucose ( 18F-FDG) uptake intensity and ranges in distinct hepatic alveolar echinococcosis lesions. Methods:The clinical data of 39 patients with position emission tomography during Jan 2017 to Dec 2019 in the First Affiliated Hospital of Xinjiang Medical University were enrolled. Among them, there were 17 males and 22 females, aging from 15 to 65 years (median 34 years). Lesions were classified into six groups based on heterogenic scales of calcification and liquefaction: A. non-calcified and non-liquefied ( n=7); B. obvious calcified and non-liquefied ( n=7); C. partial calcified and partial liquefied( n=10); D. obvious calcified and partial liquefied ( n=5); E. partial calcified and subtotal liquefied ( n=5); F. obvious calcified and subtotal liquefied ( n=5). Tumor to background ratio (TBR) and width (W) of lesion infiltrative boundary were measured and calculated. Statistical comparison using Mann-Whitney U test as well as correlation analysis was performed. Results:TBR values [ M( Q1, Q3)] for each group were 4.40(3.66, 7.03), 2.55(1.69, 3.60), 3.73(3.37, 5.21), 2.90(2.75, 3.60), 3.80(3.49, 6.36), 2.49(2.21, 3.97), among which A>B, A>D, A>F, C>B, E>B ( U=3.0, 4.0, 4.5, 11.0, 5.0, all P<0.05); From the perspective of the calcification in each group, it was found that the lighter the calcification was, the greater the TBR value was. W values [ M( Q1, Q3)] for each group were [12.5(10.0, 19.5), 11.2(10.5, 12.5), 12.2(10.9, 13.2), 7.8(7.3, 9.3), 10.0(7.3, 13.4), 7.3(6.8, 7.6)] mm, among which A>D, A>F, B>D, B>F, C>D, C>F (all U=0, all P<0.05); According to the degree of calcification and liquefaction of lesions in each group, the lighter the calcification was, the greater the W value was; The heavier the liquefaction was, the smaller the W value was. A mild strength linear correlation has been observed between the TBR value and W value ( r=0.4136, P<0.05). Conclusions:Less calcification and liquefaction implicated higher 18F-FDG uptake intensity and wider range. Radical resection margins and tissue sampling should be individualized based on different lesion features in surgical treatment.

From liver surgery to liver transplant surgery: new developments in autotransplantation.

PURPOSE OF REVIEW: In spite of substantial technical improvements and conceptual revolutions in advanced liver surgery, there are still straitened circumstances that pose difficulties for in-situ liver resections. Ex-vivo liver resection and autotransplantation (ELRA) is a hybrid technique combining experiences from conventional liver surgery and liver transplantation. This technique is becoming more comprehensive and popular among leading centers recently. RECENT FINDINGS: Short-term and long-term outcomes are now the focus of the technique after more than a decade of cumulative progress and technical evolution. As the 5-year survival nowadays reaches over 80%, this technique is believed to be beneficial for advanced tumors. In recent years, ELRA has been applied by more centers on larger scales, and the learning curve was set at 53 cases. Progresses in disease selection, surgical indications, individualized outflow reconstruction, or autograft implantation, management of co-morbidities (e.g., Budd-Chiari syndrome, caval and/or neighboring organ involvements, obstructive jaundice) propelled the development of the technique. SUMMARY: This hybrid liver surgery will benefit for carefully selected patients presented with advanced benign diseases and well-differentiated malignancies.

Single-Cell RNA Sequencing Reveals the Heterogeneity of Infiltrating Immune Cell Profiles in the Hepatic Cystic Echinococcosis Microenvironment.

Human cystic echinococcosis, caused by the larval stage of Echinococcus granulosus sensu lato, has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce a lesion microenvironment; however, cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironments are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, perilesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between perilesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of type 2 innate lymphoid cells (ILC2s) and plasmacytoid dendritic cells (pDCs) were higher in perilesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was upregulated in these cells. Seven subsets of CD4+ T cell populations were found, and there were more regulatory-CD4+ T cells (Treg-CD4+) and Th2-CD4+ T cells in perilesion tissue than in adjacent normal tissue. There was close contact between CD4+ T cells and ILC2s and pDCs, which caused upregulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A/HLA-E, was obviously higher in perilesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the cystic echinococcosis (CE) lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironments at a single-cell level and provides potential target signatures for diagnosis and immunotherapies.

Quantitative evaluation of range and metabolic activity of hepatic alveolar echinococcosis lesion microenvironment using PET/CT and multi-site sampling method.

BACKGROUND: Alveolar echinococcosis (AE) lesion microenvironment (LME) is crucial site where parasite-host interactions happen and of great significance during surgery and obtaining liver samples for basic research. However, little is known about quantification of LME range and its' metabolic activity regarding different lesion characteristics. METHODS: A prospective and retrospective analysis of LME from surgical AE patients was performed. Patients (n = 75) received abdominal computed tomography (CT) and position emission tomography/computed tomography using 18F-fluodeoxyglucose (18F-FDG-PET/CT) within 1 week prior to surgery. Semiquantitatively, calcification was clustered with 0%, < 50% and ≥ 50% degrees at lesion periphery; liquefaction was clustered with 0%, < 50%, 50 ~ 75%, ≥75% degrees at lesion center using volumetric ratio. Tumor to background ratio (TBR) of 18F-FDG standard uptake value (SUV, n = 75) was calculated, and range of 18F-FDG uptake area was measured; Multi-site sampling method (MSS, n = 35) was introduced to obtain histological slides to evaluate immune cell infiltrative ranges. RESULTS: Altogether six major lesion groups have been identified (A: 0% calcified, 0% liquefied; B: ≥50% calcified, 0% liquefied; C: < 50% calcified, < 50% liquefied; D: ≥50% calcified, < 50% liquefied; E: < 50% calcified, 50 ~ 75% liquefied; F: ≥50% calcified, ≥75% liquefied). Statistically, TBR values respectively were 5.1 ± 1.9, 2.7 ± 1.2, 4.2 ± 1.2, 2.7 ± 0.7, 4.6 ± 1.2, 2.9 ± 1.1 in groups A ~ F, and comparisons showed A > B, A > D, A > F, E > B, E > D, E > F, C > B, C > D, C > F (P < 0.05); LME ranges indicated by PET/CT respectively were 14.9 ± 3.9, 10.6 ± 1.5, 12.3 ± 1.1, 7.8 ± 1.6, 11.1 ± 2.3, 7.0 ± 0.4 mm in groups A ~ F, and comparisons showed A > B, A > D, A > F, A > E, C > B, C > D, C > F, E > D, E > F, B > D, B > F (P < 0.05); LME ranges indicated by MSS respectively were 17.9 ± 4.9, 13.0 ± 2.7, 11.9 ± 2.6, 6.0 ± 2.2, 11.0 ± 4.1, 6.0 ± 2.2 mm in groups A ~ F, and comparisons showed A > C, A > D, A > F, B > D, B > F, C > D, C > F (P < 0.05). Generally, less calcifications indicated higher TBR values and wider LME ranges; and, severer liquefactions indicated smaller LME ranges. Additionally, patients with previous medication history had lower TBR values. CONCLUSIONS: PET/CT and MSS method showed distinct TBRs and LME ranges for different calcifications and liquefactions. This study would be able to provide references for both surgical resections of lesions and more accurate sample acquisitions for basic research targeted to immunology.

Identification of infiltrating immune cell subsets and heterogeneous macrophages in the lesion microenvironment of hepatic cystic echinococcosis patients with different cyst viability.

Human cystic echinococcosis (CE) is characterized by lesion microenvironment formation through gathering various immune cells, including macrophages. However, immune cell subsets and heterogeneous macrophages in CE lesion microenvironment are poorly defined. Massive infiltrating immune cells formed lesion microenvironment, among which CD4+T cells and CD19+B cells were predominant and CD68+ macrophages were more evident in patients with active cysts. Different degrees of liver fibrosis was observed in Peri-Lesion (PL) liver samples, which was more evident in patients with active cysts. Expression of both M1 and M2 macrophage markers was significantly increased in PL liver samples. Importantly, elevation of M1 macrophage markers was more obvious in patients with inactive cysts, whereas M2 macrophage markers represented dominant macrophage phenotype in patients with active cysts. Additionally, macrophage-derived MIF, TGF-ß1 and ECM1 were also expressed at higher level in CE lesion microenvironment of patients with active cysts. Moreover, MIF was evidently enhanced in the serum of hepatic CE patients, which was also predominant in patients with active cysts. Correlation analysis demonstrated positive correlation between expression of macrophage-derived cytokines and liver fibrosis degree. Heterogeneous macrophages may play significant roles in liver fibrosis of CE lesion microenvironment through producing pro-fibrogenic cytokines.

Th1/Th2/Th17 cytokine profile in hepatic cystic Echinococcosis patients with different cyst stages.

AIMS: The study aimed to investigate possible correlation between expression level of Th1/Th2/Th17-type profile and cyst viability in the systemic and local immunity of hepatic cystic Echinococcosis (CE) patients. METHODS AND RESULTS: Expression of Th1-type interleukin (IL)-2, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, Th2-type IL-4, IL-6, IL-10 and Th17-type IL-17A was examined in the serum and liver samples of hepatic CE patients with different cyst stages. Compared with healthy controls, Th1/Th2/Th17-type cytokines were significantly increased in the serum of hepatic CE patients. Moreover, expression of these cytokines was also at higher level in the inflammatory cell band of peri-lesion liver (PL) tissues than that in the adjacent normal (AN) liver tissues. Interestingly, elevation of Th1-type and Th17-type cytokines was more evident in PL tissues of patients with inactive cysts. Relatively, Th2-type cytokines were predominant in PL tissues of patients with active cysts. CONCLUSION: Our findings provide new insights that Th1/Th2/Th2-type cytokine profile was associated with cyst stages. In hepatic CE patients with inactive cysts, Th1 and Th17-type cytokines were predominant. Comparatively, Th2-type cytokines were more evident in hepatic CE patients with active cysts, which may provide basis for the immune response diversity in hepatic CE patients with different cyst stages.

Double versus single T-tube drainage for frank cysto-biliary communication in patients with hepatic cystic echinococcosis: a retrospective cohort study with median 11 years follow-up.

BACKGROUND: Partial peri-cystectomy (PPC) is one of the major surgical approaches for hepatic cystic echinococcosis (CE) and has been practiced in most centers worldwide. Cysto-biliary communication (fistula, leakage, rupture) is a problematic issue in CE patients. T-tube is a useful technique in situations where an exploration and decompression are needed for common bile duct (CBD). However, postoperative biliary complications for cystic cavity still remains to be studied in depth. METHODS: A retrospective cohort analysis of CE cases in our single center database from 2007 March to 2012 December was performed. Patients (n = 51) were divided into two cohorts: double T-tube drainage (one at CBD for decompression and one at the fistula for sustaining in cystic cavity, n = 23) group and single T-tube drainage cohort (only one at CBD for decompression, n = 28). Short-/long-term postoperative complications focusing on biliary system was recorded in detail and they were followed-up for median 11 years. RESULTS: Overall biliary complication rates for double and single T-tube drainages were 17.4% vs. 39.3% (P > 0.05). Short-term complications ranged from minor to major leakages, cavity infection and abscess formation, and prevalence was 17.4% vs. 21.4% (P > 0.05) respectively for double and single T-tube groups; most importantly, double T-tube drainage group had obvious advantages regarding long-term complications (P < 0.05), which was biliary stricture needing surgery and it was observed only in single T-tube drainage group. CONCLUSIONS: Double T-tube drainage had better outcomes without procedure-specific postoperative biliary complications than single T-tube drainage. Meanwhile, we recommend long-term follow-up when comparing residual cavity related biliary complications in CE patients as it could happen lately.

[Simultaneous combined radical surgery for hepatic and renal alveolar echinococcosis: an analysis of 10 clinical cases].

Objective: To examine the feasibility, safety and efficacy of simultaneous combined radical surgery for hepatic and renal alveolar echinococcosis (AE). Methods: Clinical dates of consecutive 10 hepatic and renal AE patients who accepted surgical treatment in the First Affiliated Hospital of Xinjiang Medical University during April 2013 to September 2019 were analyzed retrospectively. There were 8 males and 2 females, aged (42.5±10.3) years (range: 27 to 52 years). Seven of them had previously palliative surgical treatment with poor compliance to post-operative medication. All of the patients had hepatic-renal combined AE lesions, and two of them had left lateral and left renal lesions for each, which sized for (726.4±576.1)cm3 (range: 117.0 to 1 998.0 cm3). Extra-hepatic or renal lesions infiltrated to right diaphragm, inferior vena cava, right adrenal gland, abdominal wall, right psoas muscle, duodenum wall and right pulmonary lobe (respectively were 7, 7, 6, 2, 1, 1, 2 cases). Surgery were performed mainly with simultaneous combined surgery and vascular reconstruction techniques for this series. Hemi-hepatectomy or extended right lobectomy was applied in 8 patients, while 2 other patients received ex vivo liver resection and autotransplantation, additionally, one patient had partial hepatectomy for left lateral lobular lesion. Total right nephrectomy, partial right nephrectomy and partial left nephrectomy were respectively performed on 7, 3 and 1 patient(s). Additionally, extra-hepatic or renal lesions were eradicated followed by relevant repairments or reconstructions. Results: Surgeries went well and there was no intra-or post-operative liver or renal dysfunction occurred. During recovery period, 3 cases experienced with hydrothorax and managed well after drainage and supportive treatment, and one patient developed peri-renal urinary leakage and cured by "J" catheter. The subjects were followed-up for 6 to 81 months (median: 21 months), no death, organ dysfunction, chronic or acute kidney diseases occurred. One case encountered with abdominal hernia at post-operative 7th month and was successfully managed with laparoscopic repair with artificial mesh. No disease recurrence in all patients, which reached clinical cure at last. Conclusion: When complied strictly to indications, simultaneous combined radical surgery could be a feasible, safe and efficient approach for patients with hepatic and renal AE, which is primary or relapsed from previous hepatic AE surgery or interventional therapies as well as neighboring organ AE invasions.

Current progress on lesion classification of hepatic alveolar echinococcosis / 中华肝胆外科杂志

Human alveolar echinococcosis is a chronic infectious disease caused by Echinococcus multilocularis infection. It predominantly injuries the liver and grows like the malignant tumor. The therapeutic options and prognosis depend on types of human alveolar echinococcosis, clinical stages, biological activity, vascular invasion, pathological characteristics, and patient's immune status. However, despite of multiple classification methods, there are still lacking of comprehensive typing schemes. which leads to inappropriate diagnosis and therapy. This research systematically reviewed the recent studies on human alveolar echinococcosis at home and abroad and analyzed the classifications based on ultrasound, computer tomography, magnetic resonance imaging, positron emission computed tomography, serology and pathology, and some novel technologies and summarized the individual advantage and disadvantage for each classification Relationships and their advantages plus disadvantages have been assessed comprehensively. Meanwhile, the possible reference factors or theoretical basis for optimized future classification are proposed, in order to establish a unified classification system to provide guidance for clinical diagnosis and treatment.

Multiple recurrent cystic echinococcosis with abdominal aortic involvement: A case report.

BACKGROUND: Recurrent cystic echinococcosis (CE) with vital organ involvement is a challenge for clinicians. Herein, we report a case of aortic involvement in recurrent retroperitoneal CE lesions following primary splenic CE resection. CASE SUMMARY: A 60-year-old male was admitted due to progressive abdominal pain and poor appetite. He was diagnosed with multiple recurrent CE with abdominal aortic involvement according to preoperative evaluation. During surgical resection, major aortic bleeding accidentally occurred while dissecting the cyst, which was firmly attached to the abdominal aortic wall. Hemostasis attempts were conducted to deal with this emergency situation and maintain circulation. Post-interventional recovery was uneventful, and 2-year follow-up showed no sign of recurrence or any other complications. CONCLUSION: Radical resection of recurrent complicated CE with aortic involvement should be carefully planned and performed to prevent possible severe adverse complications, thereby improving the postoperative outcome.

Direct effects of transforming growth factor-ß1 signaling on the differentiation fate of fetal hepatic progenitor cells.

Aim: To investigate direct roles of TGF-ß1 signaling in the differentiation process of fetal hepatic progenitor cells (HPCs). Materials & methods: Exogenous TGF-ß1 and SB431542 were added into fetal HPCs. Then, SB431542 was intraperitoneally injected into pregnant mice for 8 days. Results: Fetal HPCs treated with TGF-ß1 differentiated into cholangiocytes. However, hepatocyte marker was highly expressed after inhibiting TGF-ß1 signaling. In vivo, hematopoietic cells were gradually replaced with liver cells and TGF-ß1 expression was evidently decreased as fetal liver developed. Inhibition of TGF-ß1 signaling caused increase of ALB+ cells, but CK19 expression was more obvious in control mice livers. Conclusion: TGF-ß1 signaling may play decisive roles in fetal HPCs differentiation into functional hepatocytes or cholangiocytes.

Progress and applications of single-cell sequencing techniques.

Single-cell sequencing (SCS) is a next-generation sequencing method that is mainly used to analyze differences in genetic and protein information between cells, to obtain genetic information on microorganisms that are difficult to cultivate at a single-cell level and to better understand their specific roles in the microenvironment. By sequencing the whole genome, transcriptome and epigenome of a single cell, the complex heterogeneous mechanisms involved in disease occurrence and progression can be revealed, further improving disease diagnosis, prognosis prediction and monitoring of the therapeutic effects of drugs. In this study, we mainly summarized the methods and application fields of SCS, which may provide potential references for its future clinical applications, including the analysis of embryonic and organ development, the immune system, cancer progression, and parasitic and infectious diseases as well as stem cell research, antibody screening, and therapeutic research and development.

Immune Exhaustion of T Cells in Alveolar Echinococcosis Patients and Its Reversal by Blocking Checkpoint Receptor TIGIT in a Murine Model.

BACKGROUND AND AIMS: The cestode Echinococcus multilocularis infection, a serious health problem worldwide, causes alveolar echinococcosis (AE), a tumor-like disease predominantly located in the liver and able to spread to any organs. Until now, there have been few studies that explore how T-cell exhaustion contributes to the parasite's escape from immune attack and how it might be reversed. APPROACH AND RESULTS: In this study, we found that liver T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was significantly enhanced and positively correlated with lesion activity in AE patients. High TIGIT expression in both liver-infiltrating and blood T cells was associated with their functional exhaustion, and its ligand CD155 was highly expressed by hepatocytes surrounding the infiltrating lymphocytes. In co-culture experiments using human blood T cells and hepatic cell line HL-7702, CD155 induced functional impairment of TIGIT+ T cells, and in vitro blockade with TIGIT antibody restored the function of AE patients' T cells. Similar TIGIT-related functional exhaustion of hepatic T cells and an abundant CD155 expression on hepatocytes were observed in E. multilocularis-infected mice. Importantly, in vivo blocking TIGIT prevented T-cell exhaustion and inhibited disease progression in E. multilocularis-infected mice. Mechanistically, CD4+ T cells were totally and CD8+ T cells partially required for anti-TIGIT-induced regression of parasite growth in mice. CONCLUSIONS: This study demonstrates that E. multilocularis can induce T-cell exhaustion through inhibitory receptor TIGIT, and that blocking this checkpoint may reverse the functional impairment of T cells and represent a possible approach to immunotherapy against AE.

The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model.

The local immune mechanisms responsible for the establishment and development of Echinococcus granulosus sensu stricto infection in the liver, have been little explored. We developed a suitable experimental model that mimics naturally infected livers using portal injection of protoscoleces. Opposite to Echinococcus multilocularis infection which is dose-dependent, fully mature hydatid cysts can be established in the liver whatever the injection dose; although most of the infection sites were seen at the establishment phase as inflammatory granulomas associated with fibrosis, they never matured into cysts. At the establishment phase, a strong immune response was composed of T and B cells, with T1-type, T2-type cells and cytokines and IL-10-secreting CD8+ T cells in the liver. At the established phase, results suggested a local production of antibodies by B cells, and an involvement of NK and NKT cells. Infection outcome and local immune response in the liver, were different in the mouse models of Echinococcus granulosus sensu stricto and Echinococcus multilocularis respectively; however, only early specificities at the microenvironment level might explain the major differences found between the lesions induced by the two species. Our quantitative experimental model appears fully appropriate to further study this microenvironment and its relationship with each cestode species.