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.

Treatment of Cavernous Transformation of Portal Vein Caused by Hepatic Cystic Echinococcosis Using Ex Vivo Liver Resection and Autotransplantation.

BACKGROUND Hepatic cystic echinococcosis (HCE) is a frequently overlooked parasitic liver disease, for which the commonly recommended treatment is radical resection. However, this approach is often associated with severe comorbidities such as HBV/HCV, cirrhosis, and hepatic carcinoma, among others. CASE REPORT In this report, we present a case successfully managed by ex vivo liver resection and autologous liver transplantation (ELRA). In the described case, ex vivo resection was not feasible due to recurrent lesions and infections invading the portal vein, which resulted in portal vein cavernous transformation. CONCLUSIONS Through this paper, we aim to detail the treatment process, showcasing the feasibility and advantages of ELRA. Additionally, we propose a novel approach for the treatment of this disease, while emphasizing the importance of radical resection surgery to prevent long-term complications.

[Expression of neutrophil extracellular traps and phagocytic functions among patients with hepatic alveolar echinococcosis].

OBJECTIVE: To investigate the expression of neutrophil extracellular traps (NETs) and phagocytic function in the peripheral blood of patients with hepatic alveolar echinococcosis (HAE), and to examine their correlations with clinical inflamma tory indicators and liver functions. METHODS: A total of 50 patients with HAE admitted to Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qinghai University from August 2022 to June 2023 were enrolled, while 50 age- and gender-matched healthy individuals from the Centre for Healthy Examinations of the hospital during the same period served as controls. The levels of NETs markers neutrophil myeloperoxidase (MPO) and neutrophil elastase (NE) were measured using enzyme-linked immunosorbent assay (ELISA). Peripheral blood neutrophils were isolated using density gradient centrifugation, stimulated in vitro using phorbol 12-myristate 13 acetate (PMA), and the levels of MPO and citrullination histone H3 (CitH3) released by neutrophils were quantified using flow cytometry. The phagocytic functions of neutrophils were examined using flow cytometry. In addition, the correlations of MPO and NE levels with clinical inflammatory indicators and liver biochemical indicators were examined using Spearman correlation analysis among HAE patients. RESULTS: The peripheral blood plasma MPOï¼»(417.15 ± 76.08) ng/mL vs. (255.70 ± 80.84) ng/mL; t = 10.28, P < 0.05ï¼½, NEï¼»(23.16 ± 6.75) ng/mL vs. (11.92 ± 3.17) ng/mL; t = 10.65, P < 0.05ï¼½and CitH3 levelsï¼»(33.93 ± 18.93) ng/mL vs. (19.52 ± 13.89) ng/mL; t = 4.34, P < 0.05ï¼½were all significantly higher among HAE patients than among healthy controls, and a lower phagocytosis rate of neutrophils was detected among HAE patients than among healthy controlsï¼»(70.85 ± 7.32)% vs. (94.04 ± 3.90)%; t = 20.18, P < 0.05ï¼½, and the ability to produce NETs by neutrophils was higher among HAE patients than among healthy controls following in vitro PMA stimulation. Pearson correlation analysis showed that the phagocytosis rate of neutrophils correlated negatively with platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6) level and C-reactive protein (CRP) level (rs = -0.515 to -0.392, all P values < 0.05), and the MPO and NE levels positively correlated with inflammatory markers NLR, PLR, CRP and IL-6 (rs = 0.333 to 0.445, all P values < 0.05) and clinical liver biochemical indicators aspartic transaminase, alanine aminotransferase, direct bilirubin and total bilirubin among HAE patients (rs = 0.290 to 0.628, all P values < 0.001). CONCLUSIONS: Excessive formation of NETs is found among HAE patients, which affects the phagocytic ability of neutrophils and results in elevated levels of inflammatory indicators. NETs markers may be promising novel biomarkers for early diagnosis, monitoring, and severity assessment of liver disease.

Cholangiohydatidosis. Clinical features, postoperative complications and hospital mortality. A systematic review.

BACKGROUND: Cholangiohydatidosis (CH) is an evolutionary complication of hepatic cystic echinococcosis, associated with increased morbidity and mortality. The aim of this study was to describe the available evidence regarding clinical characteristics of CH, postoperative complications and hospital mortality. METHODOLOGY/PRINCIPAL FINDINGS: Systematic review. Studies related to CH with no language or publication restriction were included. Sensitive searches were performed in Trip Database, SciELO, BIREME-BVS, WoS, PubMed, EMBASE and SCOPUS. MeSH and free terms were used, including articles up to April 2023. The main outcome variables were postoperative complications and hospital mortality; the secondary ones were publication year, origin and design of primary studies, main clinical manifestation, anatomical location and type of cysts, hospital stay, surgical procedure performed, reinterventions; and methodological quality of primary studies, which was assessed using MInCir-T and MInCir-P scales. Descriptive statistics, calculation of weighted averages and their comparison by least squares logistic regression were applied. 446 studies were retrieved from the searches performed, 102 of which met the inclusion and exclusion criteria. The studies analyzed represent 1241 patients. The highest proportion of articles was published in the last decade (39.2%). Reports are mainly from Turkey (28.4%), Greece (9.8%), Morocco and Spain (8.8% each). With a weighted mean of 14.3 days of hospital stance; it was verified that 26.2% of patients developed postoperative complications (74,3% Clavien y Dindo III y IV), 6.7% needed re-interventions, and 3.7% died. When comparing the variables age, postoperative complications, hospital mortality, and reinterventions in two periods of time (1982-2006 vs. 2007-2023), no statistically significant differences were found. When applying the MInCir-T and MInCir-P scales, the methodological quality of the primary studies was 9.6±1.1 and 14.5±4.3 points, respectively. CONCLUSION/SIGNIFICANCE: CH is associated with severe postoperative complications and significant hospital mortality, independent of the development of therapeutic support associated with the passage of time.

Predictive factors of occult cystobiliary fistulas during conservative treatment of hepatic hydatid cyst: a prospective study.

BACKGROUND: Occult cystobiliary fistula (CBF) is a common complication of hepatic hydatid cyst (HHC). It is often the cause of high morbidity of conservative treatment of HHC. This study aimed to determine the predictive factors of occult CBF to establish the indications for the investigation and treatment of these CBFs. METHODS: This was a prospective study that included all operated HHCs over a 3-year period. HHCs complicated with large CBFs were not included in the study. Systematic cholecystectomy and methylene blue test for all cysts were performed. RESULTS: A total of 46 patients operated on with 113 cysts were included in this study. The median cyst size was 6.7 cm (IQR, 1-38). A total of 114 CBFs were detected in 51 cysts (45.1%). The postoperative course was simple in 95.0% of cases. The specific morbidity rate was 2.7%. In a bivariate study, absence of mass and abdominal pain on palpation, hemoglobin level >11.55 g/dL, negative hydatid serology, cyst size, absence of calcifications, vascular compression, existence of a single cyst, and localization at segment VIII were predictive factors of occult CBF. At the end of the multivariate study, cyst size was determined to be the only predictive factor for occult CBF. A threshold of 3 cm was used. CONCLUSION: Cyst size is a major predictive factor for occult CBF.

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.

Cystic Echinococcosis of the Liver: Correlation Between Intra-Operative Ultrasound and Pre-Operative Imaging.

Background: Imaging plays an essential role in the management of hepatic hydatid cysts (HCE). The objective of our study was to determine the correlation between pre-operative ultrasound, computed tomography (CT), and intra-operative ultrasound (IOUS) in studying the characteristics and complications of HCE. Patients and Methods: This was a prospective, descriptive, and analytical study conducted in the General Surgery Department of Habib Bourguiba Hospital in Sfax. The study included patients with HCE who underwent conservative surgery between April 2017 and June 2022. Results: We enrolled 49 patients with 94 cysts. At the end of our study, IOUS allowed for better detection of HCE (98.8%) regardless of the number of cysts per patient. IOUS and CT were accurate in studying the location of cysts (κ = 1), whereas pre-operative abdominal ultrasound was less efficient (κ = 0.870). IOUS was the best examination for detecting exocysts (κ = 0.961), studying daughter cysts (κ = 0.823), and exploring vascular relations, but it was less effective (κ = 0.523) in detecting calcifications. Regarding classifications, ultrasound and CT had similar results. However, IOUS was most reliable in differentiating between CE3b and CE4 types (κ = 0.653). Ultrasound, CT, and IOUS were not sensitive in detecting latent HCE suppurations and cystobiliary fistulas. Conclusions: Performing IOUS is essential to prevent recurrences and reduce post-operative morbidity.

Hidatidosis mesentérica y hepática en la costa caribe colombiana. Reporte de caso / Mesenteric and hepatic hydatid disease on the Colombian Caribbean coast. Case report

Introducción. La hidatidosis o equinococosis es una zoonosis parasitaria que se adquiere al ingerir huevos de cestodos del género Echinococcus. El diagnóstico clínico raramente se hace en sitios no endémicos. La mayoría de los pacientes se encuentran asintomáticos y los hallazgos incidentales en los estudios de imágenes o en procedimientos quirúrgicos permiten la sospecha diagnóstica. Caso clínico. Paciente masculino de 70 años, residente en área rural del municipio de Puerto Libertador, departamento de Córdoba, Colombia, quien consultó por masa abdominal en epigastrio y mesogastrio, parcialmente móvil e indolora. Resultados. En cirugía se identificaron lesiones quísticas mesentérica y hepática. Después de la cirugía y mediante estudios de inmunohistoquímica, se confirmó el diagnóstico de quiste hidatídico. El paciente tuvo una evolución satisfactoria. Conclusión. La hidatidosis quística mesentérica y hepática sintomática es una enfermedad rara en sitios no endémicos, donde la cirugía constituye un pilar fundamental en el diagnóstico y tratamiento, sumado al manejo médico farmacológico.

Introduction. Hydatidosis or echinococcosis is a parasitic zoonosis that is acquired by ingesting eggs of cestodes of the genus Echinococcus. Clinical diagnosis is rarely made in non-endemic sites. Most patients are asymptomatic and incidental findings on imaging studies or surgical procedures allow for diagnostic suspicion. Clinical case. A 70-year-old male patient, resident in a rural area of the municipality of Puerto Libertador, department of Córdoba, Colombia, who consulted for an abdominal mass in the epigastrium and mesogastrium, partially mobile and painless. Results. In surgery, mesenteric and hepatic cystic lesions were identified. After surgery and through immunohistochemistry studies, the diagnosis of hydatid cyst was confirmed. The patient had a satisfactory evolution. Conclusion. Symptomatic mesenteric and hepatic cystic hydatidosis is a rare disease in non-endemic sites, where surgery constitutes a fundamental pillar in the diagnosis and treatment in addition to pharmacological medical management.

Diagnosis and treatment experience of atypical hepatic cystic echinococcosis type 1 at a tertiary center in China.

BACKGROUND: Some hydatid cysts of cystic echinococcosis type 1 (CE1) lack well-defined cyst walls or distinctive endocysts, making them difficult to differentiate from simple hepatic cysts. AIM: To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries. METHODS: The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region (China) from January 2018 to September 2023 were retrospectively analyzed. Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis, routine abdominal ultrasound, high-frequency ultrasound, abdominal computed tomography (CT) scan, and laparoscopy. Subsequent to the treatments, these patients underwent reexaminations at the outpatient clinic until October 2023. The evaluations included the diagnostic precision of diverse examinations, the efficacy of surgical approaches, and the incidence of CE recurrence. RESULTS: All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan. Among them, 16 patients were preoperatively diagnosed with atypical CE1, and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound. All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy, of whom 14 patients were intraoperatively confirmed to have CE1, which was consistent with the postoperative pathological diagnosis, one patient was diagnosed with a mesothelial cyst of the liver, and the other was diagnosed with a hepatic cyst combined with local infection. Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts, 4 received aspiration sclerotherapy of hepatic cysts, and 19 received laparoscopic fenestration. These patients were intraoperatively diagnosed with simple hepatic cysts. During the follow-up period, none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices. One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space. CONCLUSION: Abdominal high-frequency ultrasound can detect CE1 hydatid cysts. The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE.

A Novel Technique for the Management of Persistent Biliary Fistulas Developing After Liver Hydatid Cyst Surgeries: Drain Clamping Technique.

BACKGROUND: External biliary fistula, where the residual cyst is associated with the biliary tree, is one of the most common complications after liver hydatid cyst surgery. Surgical procedures become a consideration for patients in whom the biliary fistula persists despite all endoscopic procedures. However, reoperation for biliary fistula after hydatid cyst surgery leads to additional complications and increases morbidity and mortality. AIM: This study aims to treat persistent biliary fistulas that develop after liver hydatid cyst surgery using a simple noninvasive technique. MATERIALS AND METHODS: External drainage surgery was performed on 295 patients with liver hydatid cysts. Endoscopic treatment methods were used in patients who developed biliary fistula after surgery. Despite all endoscopic treatment methods, 14 patients developed persistent biliary fistulas. These patients were subsequently treated using the drain clamping technique. FINDINGS: All persistent fistulas occluded in 11.86 days (with a range of 8-20 days). No complications were observed in the one-year follow-up visits. CONCLUSION: Drain clamping, a novel approach to the treatment of persistent biliary fistulas developed despite all available endoscopic methods, can be safely used. This technique resulted in a complete recovery in patients without the need for surgical procedures.

Severe Hypernatremia During Hydatid Cyst Surgery: An Anusual Cause Of Acute Abdomen.

Treatment of liver hydatid cysts is still in most cases surgical. To avoid the recurrence of hydatid cysts injection of scolicidal products inside the cystic cavity is an important step in the surgical procedure. Many scolicidal solutions are used. Hypertonic Saline Solution (HSS) is widely used by surgeons; however, there is a risk of hypertonic saline resorption and acute hypernatremia. Iatrogenic hypernatremia can be life-threatening. We report three cases of hypernatremia secondary to HSS injection for hydatid cyst disease treatment. The objective of this study was to discuss the clinical features, and treatment of this rare complication.

Gossypiboma mimicking hepatic hydatid cyst after 22 years: a case report.

Gossypiboma is a non-absorbable material that is forgotten during surgery. These are medicolegal pathology that leads to diagnostic confusion from abscess to tumor. We present the case of gossypiboma detected in laparotomy in a 57-year-old male patient who had a history of operation due to a hydatid cyst 22 years ago and was referred to our center due to hydatid recurrence. The case should suggest a history of surgical gossypiboma, especially in asymptomatic patients. In this preventable pathology, the strategy during sur-gery and the careful and proper attitude of the surgical team are the main determinants.

Computed tomographic appearance of canine hepatic alveolar echinococcosis.

Alveolar echinococcosis (AE) is caused by Echinococcus multilocularis, affecting dogs as accidental intermediate hosts. CT is increasingly used for abdominal imaging in small animals, providing valuable information, particularly for large masses and limited ultrasound accessibility. This study describes CT findings of hepatic lesions in 13 dogs with AE. All cases displayed well-defined cavitary lesions in the liver. Lesions showed minimal to no contrast uptake in the periphery, no uptake centrally, irregular internal walls, and soft tissue septa. Eight of 13 cases exhibited large cavitary masses (mean diameter 18.7 cm) with thick walls and feathery mineralization. Three of 13 cases had multiple smaller cavitary lesions with thin walls and without mineralization (mean diameter 8.4 cm). Two of 13 cases presented with both lesion types. These findings suggest two typical CT appearances correlated with AE: large thick-walled- and smaller thin-walled lesions. These groups may represent different stages of AE, with smaller lesions merging and progressing into larger ones. In conclusion, CT provides valuable information in evaluating hepatic lesions in dogs with AE. Large cavitary, thick-walled liver lesions with feathery wall mineralization, irregular inner margination, septation, and no central contrast uptake strongly indicate hepatic AE in dogs, differentiating it from other masses.

Viability predictive factors of the daughter vesicles in hepatic cystic echinococcosis.

INTRODUCTION: Management of cystic echinococcosis (CE) requires knowledge of certain aspects related to the survival of Echinococcus granulosus. The viability of daughter vesicles (DV) is a determining factor in guiding therapeutic indications, particularly for transiently active Cysts type CE3b. PURPOSE: To determine the predictive factors of DV viability and its impact on the therapeutic management of CE3b type. MATERIALS AND METHODS: This is a prospective pilot study with an analytical aim on patients with cystic echinococcosis of the liver type CE2 and CE3b, operated in the General Surgery Department of Habib-Bourguiba Academic Hospital, Sfax-Tunisia for 22 months from March 2018 until December 2019. The unit of the study is the DV. A parasitological study of the DV was done in the parasitology laboratory. RESULTS: During the study period, 27 (40.9%) of 66 operated CE Disease from 21 patients containing 248 DV were explored. The median viability of DV protoscoleces was 16.7%. In bivariate analysis, factors for viability of DV protoscoleces were: fever, acute cholangitis, hyperbilirubinemia, left liver location, rock water and bilious echinococcal fluid (EF), cyst size ≥ 43 mm, Intracystic pressure ≥ 35 mmHg, DV size ≥ 6.5 mm, volume, number of DV/cyst ≥ 5, and opaque wall (p < 0.05). Predictive factors for the Non-viability of DV were: CE3b type, purulent EF, gelatinous EF. In multivariate analysis, only CE2 type, cyst size ≥ 43 mm, number of DV/cyst ≥ 5 and DV size ≥ 6.5 mm were factors significantly associated with the viability of DV protoscoleces. CONCLUSION: CE3b cysts without the criteria of viability of DV protoscoleces may become candidates for the 'Wait-and-Watch' procedure.

The trajectory of anti-recEm18 antibody levels determines follow-up after curative resection of hepatic alveolar echinococcosis.

INTRODUCTION: Recurrence after curative resection of hepatic alveolar echinococcosis remains a clinical challenge. The current study tested if assessment of anti-recEm18 allows for postsurgical patient surveillance. METHODS: A retrospective study with patients undergoing liver resection for alveolar echinococcosis (n = 88) at the University Hospital Bern from 2002 to 2020 and at the University Hospital and Medical Center Ulm from 2011 to 2017 was performed. Analysis was directed to determine a potential association of pre- and postoperative values of anti-recEm18 with clinical outcomes. RESULTS: Anti-recEm18 had a linear correlation to the maximum lesion diameter (R2 = 0.558). Three trajectories of anti-recEm18 were identified based on a threshold of 10 AU/ml: "Em18-low" (n = 31), "responders" (n = 53) and "residual disease" (n = 4). The decline of anti-recEm18 in "responders" reached a plateau after 10.9 months at which levels decreased by 90%. The only patient with recurrence in the entire population was also the only patient with a secondary increase of anti-recEm18. CONCLUSION: In patients with preoperative elevated values, anti-recEm18 confirms curative surgery at 12 months follow-up and allows for long-term surveillance.

Prevalence of cystic echinococcosis in relatives of patients undergoing surgery for hepatic cystic echinococcosis in an endemic region.

BACKGROUND: Cystic echinococcosis (CE) is an endemic disease in southern Chile. The aim of this study was to ascertain the prevalence of CE among relatives of patients who underwent surgical intervention for this disease in Cautín, a province of southern Chile. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional study. Relatives of patients who underwent surgery for hepatic echinococcosis (HE), who lived at the same address, during the period 2000-2020 were studied. A total of 288 relatives of 322 patients who underwent surgery for HE participated in a CE screening. All these relatives were interviewed and underwent abdominal ultrasonography, chest X-ray and immunodiagnostic studies (relatives who had been diagnosed with or had undergone surgery for CE were excluded). Descriptive statistics were applied. Prevalence calculation, odds ratio (OR), and their respective 95% confidence intervals (95% CI) were determined. Abdominal or thoracic CE was verified in 42 relatives of subjects operated on for HE (mean age 41±8 years; 73.8% women; 38.1% of cases had two or more cysts), all of them new and asymptomatic cases. CE was detected in the lungs, liver, peritoneum, and spleen in 16.7%; 71.4%; 7.1%; and 4.8%, respectively. The overall prevalence of EQ during the studied time period was 14,6% (17.9% and 12.3% in relatives of first and second degree respectively (OR:1.56; CI 95%: 0.81; 3.01). CONCLUSION/SIGNIFICANCE: There is a high prevalence of CE in relatives of patients undergoing surgery by this disease in the province of Cautín, Chile.