Natural History of Hepatosplenic Schistosomiasis (HSS) Non-Cirrhotic Portal Hypertension (NCPH): Influence of Gastrointestinal Bleeding and Decompensation in Prognosis.

BACKGROUND: Hepatosplenic schistosomiasis (HSS) is a peculiar form of non-cirrhotic portal hypertension (NCPH). Although HSS patients present normal hepatic function, some evolve signs of hepatocellular failure and features of decompensated cirrhosis. The natural history of HSS-NCPH is unknown. METHODS: A retrospective study was conducted that evaluated patients who fulfilled clinical-laboratorial criteria for HSS. RESULTS: A total of 105 patients were included. Eleven patients already presented with decompensated disease and had lower transplant-free survival at 5 years than those without (61% vs. 95%, p = 0.015). Among 94 patients without prior decompensation, the median follow-up was 62 months and 44% of them had varicose bleeding (two or more episodes in 27%). Twenty-one patients presented at least one episode of decompensation (10-year probability 38%). Upon multivariate analysis, varicose bleeding and higher bilirubin levels were associated with decompensation. The 10-year probability of survival was 87%. Development of decompensation and age were predictive of mortality. CONCLUSION: HSS is characterized by multiple episodes of GI bleeding, a high probability of decompensation and reduced survival at the end of the first decade. Decompensation is more common in patients with varicose esophageal bleeding and is associated with lower survival.

Sarcopenia, body composition and factors associated with variceal gastrointestinal bleeding and splenectomy in hepatosplenic schistosomiasis mansoni.

BACKGROUND: Sarcopenia is a common complication of cirrhosis and an important predictor of morbimortality. We aimed to determine the prevalence of sarcopenia and its associated factors in hepatosplenic schistosomiasis (HSS) as well as to evaluate whether muscle mass and function are associated with variceal upper gastrointestinal bleeding (VUGIB) and previous splenectomy in subjects without other liver diseases. METHODS: We conducted a cross-sectional study including adults with HSS who underwent clinical, biochemical, anthropometric, muscle strength and physical performance evaluations and were submitted to bioelectrical impedance analysis and abdominal ultrasound. Sarcopenia was diagnosed according to the 2019 European consensus criteria. RESULTS: A total of 66 patients with HSS (62.1% male; mean age 48.8±8.6 y) were included. Overall, six subjects (9.1%) were diagnosed with probable sarcopenia and none had confirmed sarcopenia. Fat-free body mass index (BMI) was independently associated with VUGIB (odds ratio 0.701 [95% confidence interval 0.51 to 0.96]; p=0.025). Compared with patients who did not undergo surgery, individuals who underwent esophagogastric devascularization combined with splenectomy (EGDS) had higher serum lipid levels, fat percentage and frequency of metabolic syndrome, with lower skeletal muscle mass index and hand grip strength. CONCLUSIONS: HSS mansoni seems not to cause sarcopenia. However, a lower fat-free BMI was associated with previous VUGIB and the subgroup of patients who underwent EGDS presented higher lipid levels, fat percentage and frequency of metabolic syndrome and lower muscle mass and function.

Noninvasive predictors of esophageal varices in patients with hepatosplenic schistosomiasis mansoni.

BACKGROUND: No previous study have evaluated transient elastography for predicting esophageal varices in hepatosplenic schistosomiasis. AIM: To investigate noninvasive methods of predicting esophageal varices in patients with hepatosplenic schistosomiasis mansoni. METHODS: Cross-sectional multicentric study included 51 patients with hepatosplenic schistosomiasis. Patients underwent ultrasonography-dopplerfluxometry, upper endoscopy, complete blood cell count and transient elastography (Fibroscan®) for liver and spleen stiffness measurement (LSM and SSM). Noninvasive scores previously established for cirrhotic population were studied: platelet count to spleen diameter ratio (PSR), LSM-spleen diameter to platelet ratio score (LSPS) and varices risk score (VRS). We proposed a version of LSPS and VRS by replacing LSM with SSM and named them SSPS and modified-VRS, respectively. RESULTS: Esophageal varices were detected in 42 (82.4%) subjects. Individuals with varices presented higher SSM (73.5 vs 36.3 Kpa, p = 0.001), splenic vein diameter (10.8 vs 8.0 mm, p = 0.017), SSPS (18.7 vs 6.7, p = 0.003) and modified-VRS (4.0 vs 1.4, p = 0.013), besides lower PSR (332 vs 542, p = 0.038), than those without varices. SSPS was independently associated with varices presence (OR=1.19, 95%CI 1.03-1.37, p = 0.020) after multivariate analysis. In a model excluding noninvasive scores, SSM was independently associated with varices diagnosis (OR=1.09, 95%CI 1.03-1.16, p = 0.004). AUROC was 0.856 (95%CI 0.752-0.961, p = 0.001) for SSM and 0.816 (95%CI 0.699-0.932, p = 0.003) for SSPS (p = 0.551). CONCLUSIONS: Spleen-related variables were predictors of esophageal varices: SSM, splenic vein diameter, SSPS, modified-VRS and PSR. Multivariate models indicated that SSM and SSPS are useful tools for predicting varices in non-cirrhotic portal hypertension by hepatosplenic schistosomiasis and may be used in clinical practice.

Liver stiffness is able to differentiate hepatosplenic Schistosomiasis mansoni from liver cirrhosis and spleen stiffness may be a predictor of variceal bleeding in hepatosplenic schistosomiasis.

BACKGROUND: Ultrasonography is limited for differentiating portal hypertension due to liver cirrhosis from that secondary to hepatosplenic schistosomiasis (HSS). We aimed to investigate the role of transient elastography (TE) in differentiating HSS mansoni from cirrhosis and the factors associated with liver and spleen stiffness (LS and SS) in HSS. METHOD: A cross-sectional study was conducted including patients with HSS mansoni (n=29) and liver cirrhosis due to non-alcoholic steatohepatitis (n=23). All patients underwent TE and those with HSS were assessed by the Niamey protocol. RESULTS: HSS subjects presented lower median LS (9.6 vs 21.3 Kpa, p<0.001) and liver controlled attenuation parameter (229 vs 274 dB/m, p=0.010) than cirrhosis subjects, in addition to higher SS (73.5 vs 42.2 Kpa, p=0.002). The area under the receiver operating characteristic curve for detecting cirrhosis by LS was 0.947 (95% CI 0.89 to 1.00, p<0.001), with an optimal cut-off of 11.75 Kpa. In HSS subjects, higher SS was associated with the presence of the following: diabetes mellitus (p=0.036), metabolic syndrome (p=0.043), esophageal varices (p=0.001), portal vein thrombosis (p=0.047) and previous variceal bleeding (p=0.011). In HSS patients without portal vein thrombosis, variceal bleeding was associated with higher SS (p=0.018). Niamey categories were not associated with LS (p=0.676) or SS (p=0.504). CONCLUSION: TE can play a role in differentiating HSS from cirrhosis, especially by LS. SS may be further investigated for predicting complications in HSS.

Schistosome-Associated Pulmonary Arterial Hypertension: A Review Emphasizing Pathogenesis.

Schistosomiasis, especially due to Schistosoma mansoni, is a well-recognized cause of pulmonary arterial hypertension (PAH). The high prevalence of this helminthiasis makes schistosome-related PAH (Sch-PAH) one of the most common causes of this disorder worldwide. The pathogenic mechanisms underlying Sch-PAH remain largely unknown. Available evidence suggests that schistosome eggs reach the lung via portocaval shunts formed as a consequence of portal hypertension due to hepatosplenic schistosomiasis. Once deposited into the lungs, the eggs elicit an immune response resulting in periovular granuloma formation. Immune mediators drive transforming growth factor-ß (TGF-ß) release, which gives rise to pulmonary vascular inflammation with subsequent remodeling and development of angiomatoid and plexiform lesions. These mechanisms elicited by the eggs seem to become autonomous and the vascular lesions progress independently of the antigen. Portopulmonary hypertension, which pathogenesis is still uncertain, may also play a role in the genesis of Sch-PAH. Recently, there have been substantial advances in the diagnosis and treatment of PAH, but it remains a difficult condition to recognize and manage, and patients still die prematurely from right-heart failure. Echocardiography is used for screening, and the formal diagnosis requires right-heart catheterization. The experience in treating Sch-PAH is largely limited to the phosphodiesterase type 5 inhibitors, with evidence suggesting that these vasodilators improve symptoms and may also improve survival. Considering the great deal of uncertainty about Sch-PAH pathogenesis, course, and treatment, the aim of this review is to summarize current knowledge on this condition emphasizing its pathogenesis.

Quality of Life Assessment Among Patients Living With Hepatosplenic Schistosomiasis and Schistosomal Myeloradiculopathy.

Schistosomiasis is a major public health problem in tropical areas of the world. Health-related quality of life (HRQOL) measurement is being widely used to evaluate the impact of a disease or treatment in several aspects of daily life. However, few studies evaluated the impact of severe forms of schistosomiasis on HRQOL of affected individuals and compared them to healthy controls with a similar socio-demographic background. Our aims were to evaluate the HRQOL in patients with hepatosplenic schistosomiasis (HS) and schistosomal myeloradiculopathy (SMR) and healthy volunteers (HV) and determine if clinical complications of the disease are associated with HRQOL scores. We interviewed and evaluated the HRQOL in 49 patients with HS, 22 patients with SMR, and 26 HV from an outpatient clinic of the Federal University of Minas Gerais University Hospital using the WHOQOL-BREF questionnaire. SMR and HS patients had a significantly lower overall quality of life score when comparing with the HV control group (p = 0.003 and p = 0.005, respectively). Multivariate ordinal regression model adjusted for sex, age, and educational level indicated that HS and SMR patients have three and five times more chances of having a lower quality of life than healthy volunteers (Odds Ratio 3.13 and 5.04, respectively). There was no association between complications of HS disease and quality of life scores. In contrast, worse quality of life was observed in SMR patients that presented back or leg pain, leg paresthesia, and bladder dysfunction. In conclusion, HS and SMR significantly impact the overall quality of life of the affected individuals, reinforcing the importance of efforts to control and eradicate this debilitating disease and suggesting that multidisciplinary clinical management of schistosomiasis patients would be more appropriate and could potentially improve patient's quality of life.

EDTA-dependent pseudothrombocytopenia in patients with hepatosplenic schistosomiasis mansoni: a clinical management alert.

BACKGROUND: Hepatosplenic schistosomiasis mansoni (HS) is associated with thrombocytopenia. Accurate platelet counts are required for identification and management of HS patients. EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is an in vitro phenomenon of anticoagulant-activated platelet agglutination resulting in low platelet counts by automated methods. The prevalence of EDTA-PCTP in schistosomiasis is unknown and only one case has been described. Our aims were to determine the prevalence of EDTA-PTCP in HS and evaluate alternative methods to overcome this analytical error. METHODS: Blood samples from 56 HS patients and 56 healthy volunteers were collected, and platelet counts were obtained using standard microscopy and automated (electric impedance) methods. Automated platelet counts and the presence of platelet clumps in blood smears were evaluated in samples collected in EDTA or sodium citrate tubes 20 and 180 min after blood collection. RESULTS: EDTA-PTCP was more frequent in HS patients than healthy volunteers (8.92% vs 0.00%, p<0.0285). Platelet clumps and PTCP were also observed in samples collected in sodium citrate tubes, refuting its use as an alternative method. CONCLUSIONS: Automated platelet counts in blood samples from HS patients should be performed right after blood collection in EDTA tubes and verified by manual counts in blood smears.

Aquaporin-2 and NKCC2 expression pattern in patients with hepatosplenic schistosomiasis.

OBJECTIVE: Schistosoma mansoni infection is considered a public health problem. Glomerular involvement in schistosomiasis is a well-documented complication, especially in hepatosplenic schistosomiasis (HSS). However, renal tubular function is poorly understood. The aim of this study was to investigate, through urinary exosomes, tubular transporters functionally in HSS patients. METHODS: Cross-sectional study of 20 HSS patients who had isolated exosomes from urine samples. Protease inhibitor was added in the urine samples who were immediately frozen at -80 °C for further exosomes isolation. After urine had thawed, urinary exosomes were obtained using extensive vortexing, centrifugation and ultracentrifugation steps of urine. Urinary transporters expression from exosomes was evaluated by western blot, including NHE3, AQP2 and NKCC2. Charge amounts for gel electrophoresis were adjusted by urinary creatinine concentration of each patient to avoid urinary concentration bias. All protein expression of HSS patients was relative to healthy controls. RESULTS: The expression of aquaporin-2 (AQP2) was lower in HSS patients than in controls (46.8 ± 40.7 vs. 100 ± 70.2%, P = 0.03) and the expression of the NKCC2 co-transporter was higher (191.7 ± 248.6 vs. 100 ± 43.6%, P = 0.02). CONCLUSIONS: The decrease of AQP2 and the increase of NKCC2 expression in HSS patients seem to be involved with the inability of urinary concentration in these patients. These data show renal tubular abnormalities in HSS patients without manifest clinical disease.

OBJECTIF: L'infection à Schistosoma mansoni est considérée comme un problème de santé publique. L'atteinte glomérulaire dans la schistosomiase est une complication bien documentée, en particulier dans la schistosomiase hépatosplénique (SH). Cependant, la fonction tubulaire rénale est mal connue. Le but de cette étude était d'étudier, par le biais d'exosomes urinaires, les transporteurs tubulaires fonctionnellement chez les patients atteints de SH. MÉTHODES: Il s'agit d'une étude transversale sur 20 patients atteints de SH qui avaient des exosomes isolés d'échantillons d'urine. Un inhibiteur de protéase a été ajouté dans les échantillons d'urine qui ont été immédiatement congelés à -80°C pour un isolement supplémentaire des exosomes. Après décongélation de l'urine, des exosomes urinaires ont été obtenus en utilisant des étapes étendues de vortex, de centrifugation et d'ultracentrifugation d'urine. L'expression des transporteurs urinaires d'exosomes a été évaluée par western blot, y compris NHE3, AQP2 et NKCC2. Les quantités de charge pour l'électrophorèse sur gel ont été ajustées par la concentration de créatinine urinaire de chaque patient pour éviter un biais de concentration urinaire. Toute expression protéique des patients atteints de SH était relative à celle de témoins sains. RÉSULTATS: L'expression de l'aquaporine-2 (AQP2) était plus faible chez les patients SH que chez les témoins (46,8 ± 40,7 vs 100 ± 70,2%, P = 0,03) et l'expression du co-transporteur NKCC2 était plus élevée (191,7 ± 248,6 vs 100 ± 43,6%, P = 0,16). CONCLUSIONS: La diminution de l'AQP2 et l'augmentation de l'expression de NKCC2 chez les patients SH semblent être impliquées dans l'incapacité de concentration urinaire chez ces patients. Ces données montrent des anomalies tubulaires rénales chez les patients SH sans maladie clinique manifeste.

Morbidity of schistosomiasis mansoni in a low endemic setting in Ouro Preto, Minas Gerais, Brazil

Abstract INTRODUCTION: Despite the advances of disease control programs, severe forms of schistosomiasis are prevalent. The prevalence of the disease in areas frequented by tourists urges for permanent prevention and control. The aim of this study was to describe the morbidity of schistosomiasis in the district of Antônio Pereira, Ouro Preto, Minas Gerais, Brazil. METHODS: The proportion of positives was defined by Kato-Katz coproscopy and urinary POC-CCA rapid test. Hepatosplenic form was diagnosed using abdominal ultrasound. RESULTS: Out of 180 participants,97 were examined by Kato-Katz, with 4 (4.1%) being positive. Thirty-four (22.1%) out of 154 were positive by POC-CCA. Five (2.8%) of 177 examined by ultrasound had hepatosplenic form. One of them had undergone splenectomy. One (0.6%)participant had myeloradiculopathy. CONCLUSIONS: Severe forms of schistosomiasis are still prevalent in low endemic areas and should be thoroughly investigated.

Sensitivity and specificity of the circulating cathodic antigen rapid urine test in the diagnosis of Schistosomiasis mansoni infection and evaluation of morbidity in a low- endemic area in Brazil

Abstract INTRODUCTION: The Kato-Katz technique is the standard diagnostic test for Schistosoma mansoni infection in rural areas. However, the utility of this method is severely limited by the day-to-day variability in host egg excretion in the stool. In high-transmission areas, the point-of-care circulating cathodic antigen (POC-CCA) urine assay has proven to be a reliable test. However, investigations of the reliability of the POC-CCA assay in low-transmission regions are under way. This study aimed to evaluate the sensitivity and specificity of the POC-CCA assay and the morbidity of schistosomiasis in a low-endemic area in Brazil. METHODS: Pains City is a low-transmission zone for schistosomiasis. A total of 300 subjects aged 7-76 years were randomly selected for the POC-CCA cassette test. For S. mansoni diagnosis, three stool samples on six slides were compared with one urine sample for each subject. The sensitivity and specificity in the absence of a gold standard were calculated using latent class analysis. Clinical examinations and abdominal ultrasounds were performed in 181 volunteers to evaluate morbidity associated with schistosomiasis. RESULTS: The sensitivity and specificity of the Kato-Katz technique were 25.6% and 94.6%, respectively. By contrast, the sensitivity and specificity of the POC-CCA assay were 68.1% and 72.8%, respectively. Hepatosplenic schistosomiasis was diagnosed in two patients (1.1%). CONCLUSIONS: Overall, the POC-CCA urine assay proved to be a useful test for diagnosing S. mansoni in a low-endemic area in Brazil. Severe clinical forms of schistosomiasis can be present even in such low-endemic areas.

Increased Hepatic Arterial Blood Flow Measured by Hepatic Perfusion Index in Hepatosplenic Schistosomiasis: New Concepts for an Old Disease.

BACKGROUND: Portal vein obstructive lesions associated with hypertrophy of the hepatic artery territory are observed in Schistosoma mansoni schistosomiasis. Liver perfusion scintigraphy is a method used for evaluation of hepatic perfusion changes in liver diseases. It has been suggested that, like in cirrhosis, where compensatory increase in perfusion through the hepatic artery is documented, perfusion changes occur in hepatosplenic schistosomiasis (HSS). AIMS: This study aims to determine changes in liver hemodynamics using hepatic perfusion scintigraphy and correlate them with clinical and laboratory variables and ultrasound findings in HSS. METHODS: Nineteen patients with schistosomiasis underwent ultrasound evaluation of degree of liver fibrosis, splenic length, and splenic and portal vein diameter, digestive endoscopy, and quantification of platelets. Subsequently, perfusion scintigraphy with measurement of hepatic perfusion index (HPI) was performed. RESULTS: It was observed that patients with hepatosplenic schistosomiasis had significantly higher HPI compared with normal individuals (p = 0.0029) and that this increase correlated with splenic length (p = 0.038) and diameter of esophageal varices (p = 0.0060). Angioscintigraphy showed high accuracy for predicting presence of large esophageal varices. CONCLUSIONS: Angioscintigraphy could show that patients with HSS had increased HPI, featuring greater liver "arterialization," as previously described for cirrhotic patients. Correlations were also observed between HPI and longitudinal splenic length, caliber of esophageal varices, caliber of portal vein, and blood platelet count. Angioscintigraphy is a promising technique for evaluation of hepatosplenic schistosomiasis.

Participação da via do Hedgehog na fibrose hepática da esquistossomose mansoni humana e murina experimental / Participation via the Hedgehog in liver fibrosis of human schistosomiasis and experimental murine

INTRODUÇÃO/OBJETIVO: A esquistossomose mansonica é causa importante de fibrose hepática e hipertensão porta em regiões tropicais, e a patogênese da fibrose não está bem esclarecida. Como a via do hedgehog e um dos seus genes alvos,a osteopontina, estão envolvidos em fibroses hepáticas de outras etiologias o objetivo foi investigar a ativação destas vias na esquIsitossomose humana e murina experimental, no intuito de verificar o seu envolvimento no desenvolvimento da forma hepatoesplênica da esquistossomose mansonica (FHE). MATERIAL E MÉTODOS: 87 biópsias em cunha de fígados de pacientes com FHE submetidos a cirurgia e fragmentos de fígado de camundongos suiços infectados com Schistosoma mansoni foram submetidos a métodos imunohistoquímicos e de biologia molecular para avaliar a expressão de ligantes hedgehog (Ihh, Shh), receptor Patched, fatores de transcrição Gli 1 e 2 e osteopontina. Osteopontina sérica e ligante Shh do hedgehog foram avaliados em camundongos suíços infectados e os de osteopontina em camundongos CBA/J infectados e em pacientes com FHE e forma hepatointestinal da esquistossomose. In vitro foi avaliado o efeito de antígeno solúvel do ovo (SEA) em células de Kuppfer, células estreladas, macrófagos, colangiócitos e células endoteliais sinusoidais hepáticas. A relação com a via da IL-13 foi avaliada em camundongos geneticamente deficientes ou hiperexpressando a citocina. Foi avaliado in vitro se a IL-13 induz ligantes hedghog ou ativação da via em células de Kuppfer. RESULTADOS: Os resultados mostraram: (a) aumento expressão de ligantes Ihh, de fatores de transcrição Gli2 e de osteopontina no fígado de camundongos suíços infectados com Schistosoma mansoni, aumento de shh e osteopontina no plasma de camundongos suíços e de osteopontina no plasma de camundongos CBA/J infectados com S. mansoni; (b) aumento na expressão de Ihh, Shh, Gli1 e 2, receptor Patched e de osteopontina no fígado de pacientes com esquistossomose e aumento da osteopontina sérica em pacientes com a FHE; (c) A expressão de ligantes hedgehog e de Gli2 foi observada em macrófagos, células estreladas, ductos biliares e células endoteliais, e a de osteoponina em ductos biliares,macrófagos e células estreladas/miofibroblastos; (d) correlação positiva entre ativação do hedgehog (Gli2 e osteopontina) e fibrose, no modelo murino experimental e nos pacientes; nestes a correlação também foi observada com o grau de fibrose classificada pelo ultrassom e com a hipertensão porta; (e) Inibição in vitro do hedgehog com ciclopamina e vismodegib ou por nocauteamento condicional de receptor Smoothened bloqueou a ativação alternativa de macrófagos e inibiu a angiogênese a partir de células endoteliais sinusoidais hepáticas; (f) que o bloqueio da via da IL-13 reduziu e a hiperexpressão aumentou a ativação da via do hedgehog e IL-13 diretamente induziu, in vitro,produção de ihh em células de Kupffer de camundongos e de humanos, demonstrando a inter-relação das duas vias...

BACKGROUND AND AIMS: Schistosomiasis is a major cause of liver fibrosis and portal hypertension in tropical regions, and the pathogenesis of fibrosis is not well established. As hedgehog pathway and one of its target genes, osteopontin, are involved in liver fibrosis of other etiologies our aims were to investigate the activation of these pathways in human and experimental murine schistosomiasis, in an attempt to verify their involvement in the development of hepatosplenic schistosomiasis mansoni (HS). METHODS: 87 wedge liver biopsies of patients with HS submitted to surgery and liver fragments Swiss mice infected with Schistosoma mansoni were submitted to immunohistochemistry and molecular biology methods to evaluate the expression of hedgehog ligands (Ihh, Shh), patched receptor , Gli transcription factors and osteopontin. Serum osteopontin and Shh were evaluated in infected Swiss mice and osteopontin was evaluated in serum of infected CBA/J mice and plasma from patients with hepatointestinal and HS forms of schistosomiasis. The effect of soluble egg antigen (SEA) on Kuppfer cells, stellate cells, macrophages, cholangiocytes and liver sinusoidal endothelial cells was evaluated in vitro. Relationship with IL-13 pathway was evaluated in mice genetically deficient or with hyperexpression of this cytokine. Whether IL-13 induces production of ligands and/or activation of the hedgehog pathway in Kuppfer cells was evaluated in vitro. RESULTS: Results demonstrated: (a) increased expression of Ihh, transcription factor Gli2 and osteopontin in the livers of Swiss mice infected with S. mansoni, increased plasma levels of shh and osteopontin in infected Swiss mice and increased osteopontin in plasma of S. mansoni infected CBA/J mice; (b) increased expression of ihh, shh, Gli1 and 2, patched and osteopontin receptor in the liver of patients with schistosomiasis and increased serum osteopontin in patients with HS; (c) expression of hedgehog ligands and Gli2 was observed in macrophages, stellate cells, endothelial cells and bile duct and expression of osteopontin was detected in macrophages and stellate/myofibroblast cells; (d) positive correlation between activation of the hedgehog (Gli2 and osteopontin) and fibrosis in experimental murine model and in patients; these correlation was also observed with the degree of fibrosis classified by ultrasound and with portal hypertension; (e) in vitro inhibition of hedgehog pathway with cyclopamine or vismogedib or by conditional knockout of Smoothened co-receptor blocked the alternative activation of macrophage and inhibited angiogenesis in liver sinusoidal endothelial cells; (f) reduction of IL-13 pathway or IL-13 over-expression respectively reduced or increased the activation of the hedgehog pathway and IL-13 directly induced in vitro ihh production in Kupffer cells from mice and human, demonstrating a cross-talk between the two pathways...

Participação da via do Hedgehog na fibrose hepática da esquistossomose mansoni humana e murina experimental / Participation via the Hedgehog in liver fibrosis of human schistosomiasis and experimental murine

INTRODUÇÃO/OBJETIVO: A esquistossomose mansonica é causa importante de fibrose hepática e hipertensão porta em regiões tropicais, e a patogênese da fibrose não está bem esclarecida. Como a via do hedgehog e um dos seus genes alvos, a osteopontina, estão envolvidos em fibroses hepáticas de outras etiologias o objetivo foi investigar a ativação destas vias na esquIsitossomose humana e murina experimental, no intuito de verificar o seu envolvimento no desenvolvimento da forma hepatoesplênica da esquistossomose mansonica (FHE). MATERIAL E MÉTODOS: 87 biópsias em cunha de fígados de pacientes com FHE submetidos a cirurgia e fragmentos de fígado de camundongos suiços infectados com Schistosoma mansoni foram submetidos a métodos imunohistoquímicos e de biologia molecular para avaliar a expressão de ligantes hedgehog (Ihh, Shh), receptor Patched, fatores de transcrição Gli 1 e 2...

inglês: BACKGROUND AND AIMS: Schistosomiasis is a major cause of liver fibrosis and portal hypertension in tropical regions, and the pathogenesis of fibrosis is not well established. As hedgehog pathway and one of its target genes, osteopontin, are involved in liver fibrosis of other etiologies our aims were to investigate the activation of these pathways in human and experimental murine schistosomiasis, in an attempt to verify their involvement in the development of hepatosplenic schistosomiasis mansoni (HS). METHODS: 87 wedge liver biopsies of patients with HS submitted to surgery and liver fragments Swiss mice infected with Schistosoma mansoni were submitted to immunohistochemistry and molecular biology methods to evaluate the expression of hedgehog ligands (Ihh, Shh), patched receptor , Gli transcription factors and osteopontin...

Revisiting the concept of hepatosplenic schistosomiasis and its challenges using traditional and new tools

Different aspects of hepatosplenic schistosomiasis are revisited here. Manson's schistosomiasis causes periportal fibrosis and portal hypertension in approximately 6% of infected subjects, usually with preservation of their hepatic function. The assessment of liver involvement is of major importance in determining the prognosis and risk of complications from schistosomiasis, such as upper digestive bleeding secondary to variceal rupture. For many years, the diagnosis of hepatosplenic schistosomiasis and liver fibrosis was made by abdominal palpation and the finding of liver and/or spleen enlargement. However, there is no consensus regarding the clinical parameters of the liver and spleen to be considered in this physical evaluation. For the last three decades, abdominal ultrasound (US) has become the best imaging technique to evaluate liver fibrosis caused by schistosomiasis mansoni. However, US is a subjective procedure and is therefore examiner-dependent. Magnetic resonance imaging (MRI) findings have provided valuable information in addition to ultrasound and clinical examination. The combination of a comprehensive history and physical examination, basic laboratory tests (a stool examination for Schistosoma mansoni eggs and a blood cell count), biomarkers for liver fibrosis/portal hypertension and imaging methods seem to offer the best approach for evaluating patients with this disease. In situations where research is involved or in patients with severe disease, MRI may be considered.

Thrombocytopenia as a surrogate marker of hepatosplenic schistosomiasis in endemic areas for Schistosomiasis mansoni

Introduction This study aimed to evaluate whether a low platelet count is a good surrogate marker of hepatosplenic schistosomiasis (HSS) in a rural area of Brazil. A small district in southeastern Brazil, with a population of 1,543 individuals and a 23% prevalence of schistosomiasis, was selected for this investigation. Methods In July 2012, 384 volunteers were subjected to clinical, ultrasonography (US), and laboratory examinations, including stool sample analysis. The HSS patients were classified into four groups: Group 1 consisted of patients with a spleen >13cm and liver fibrosis; Group 2 consisted of patients with a palpable spleen and spleen>13cm measured by US; Group 3 consisted of patients with a spleen >13cm measured by US; and Group 4 consisted of patients with a palpable spleen. Results Eight patients were in Group 1 (2.1%), twenty-one were in Group 2 (5.5%), eight were in Group 3 (2.1%), and eighteen were in Group 4 (4.7%). A significant difference in the mean platelet counts was observed between the patients with and without HSS (p<0.01). Based on the receiver operating characteristic (ROC) curve (platelet count <143,000/mm3), the sensitivity was greater than 92% in all groups, and the specificity varied from 44.4% to 75%. Conclusions We concluded that in endemic areas, thrombocytopenia demonstrates good sensitivity for detecting HSS and may be used as a screening tool to identify patients with HSS. .

Métodos de imagem no diagnóstico de esquistossomose hepatoesplânica / Imaging techniques in the diagnosis of hepatosplenic schistosomiasis

A esquistossomose constitui grave problema de saúde pública, com mais de 200 milhões de infectados no mundo. Deste total, cerca de 10% desenvolvem a forma hepatoesplênica da doença caracterizada por fibrose periportal e hipertensão porta. No passado, o diagnóstico da esquistossomose hepatoesplênica (EHE) era realizado por métodos invasivos como esplenoportografia e biópsia hepática. O estudo das alterações no sistema porta e da morfologia hepática e esplênica com métodos de imagem representou um avanço significativo no diagnóstico da doença. Os métodos mais utilizados atualmente são a ultrassonografia abdominal, a ressonância nuclear magnética e a tomografia computadorizada de abdomen. O objetivo do presente artigo é abordar as principais contribuições de cada método no diagnóstico da EHE.

Schistosomiasis is a serious public health problem with over 200 million infected worldwide. Nearly 10% of infected individuals develop the hepatosplenic form of the disease characterized by periportal fi brosis and portal hypertension. In the past, the diagnosis of hepatosplenic schistosomiasis (HHS) was performed by invasive methods such as liver biopsy and splenoportography. The study of changes in portal system and morphological aspects of liver and spleen with imaging techniques represented a significant advance in the diagnosis of the disease. The most widely used techniques are abdominal ultrasonography, magnetic resonance imaging and computed tomography of the abdomen. The aim of this article is to discuss the main contribution of each technique in the diagnosis of HHS.

Splenosis after splenectomy and spleen tissue autoimplantation: Late followup study.

AIM: In children suffering from severe hepatosplenic schistosomiasis, the surgical protocol includes splenectomy and autoimplantation of spleen morsels in the major omentum, which has the potential of reducing the overwhelming postsplenectomy infection (OPSI). The purpose of the study was to evaluate the remaining splenosis, with the mean postoperative followup of 12.1 ± 5.6 years; to compare the efficacy of the 2 evaluation tools. MATERIALS AND METHODS: Nineteen patients underwent, when they were children, portal decompression and autoimplantation of spleen. After a mean age of 23.4 ± 5.3 years, they were investigated regarding the number of infections and OPSI. They had undergone hepatosplenic scintigraphy with labeled colloidal SnTc(99m) and abdominal ultrasound. It was considered efficient splenosis when the patients presented with 5 or more spleen nodules. The evaluation was performed by 3 observers. RESULTS: None of the patients had increased infection rate or developed OPSI. Sixteen (84.2%) presented efficient splenosis. CONCLUSIONS: The remaining postoperative splenosis was considered efficient in the majority of patients in the long-term followup; and nuclear medicine was considered the gold standard for splenosis evaluation.

Serum hyaluronan and collagen IV as non-invasive markers of liver fibrosis in patients from an endemic area for schistosomiasis mansoni: a field-based study in Brazil

Non-invasive markers of fibrosis have been used to diagnose liver fibrosis in a variety of diseases. Hyaluronic acid (HA) and collagen IV (C-IV) levels were measured in the sera of patients from an endemic area for schistosomiasis in Brazil to diagnose and to rank the intensity of liver fibrosis. Seventy-nine adult patients with schistosomiasis, in the age range of 21-82 years (49 ± 13.4) were submitted to clinical and ultrasonographic examinations. Ultrasound was employed to diagnose and categorise liver fibrosis according to World Health Organization patterns. Serum HA and C-IV levels were measured using commercial ELISA kits. Ultrasound revealed six patients with intense liver fibrosis, 21 with moderate, 23 with light and 29 without. Serum HA was able to separate individuals with fibrosis from those without (p < 0.001) and light from intense fibrosis (p = 0.029), but C-IV was not (p = 0.692). The HA diagnostic accuracy for fibrosis was 0.89. The 115.4 ng/mL cut-off level diagnosed patients with fibrosis (sensitivity 0.98, specificity 0.64). HA correlated positively with portal hypertension. Periportal fibrosis (subjective evaluation), age and collateral circulation predicted HA increase. In conclusion, we propose that serum HA can be used to identify patients with liver fibrosis in an endemic area for schistosomiasis mansoni in Brazil.

Ultrasound in schistosomiasis mansoni

We reviewed ultrasound features in patients with schistosomiasis mansoni. The alterations that we observed in acute and hepatosplenic schistosomiasis are described. The advantages and disadvantages of using ultrasound patterns in the evaluation of liver fibrosis are discussed. Other diseases that are important in the differential diagnosis of schistosomal liver fibrosis are presented. Ultrasound is an effective and flexible diagnostic tool in the evaluation of a variety of diseases. It presents no harmful effects to patients, allowing non-invasive studies in hospitalized patients and in other facilities.

Schistosomiasis control program in the state of Minas Gerais in Brazil

The Schistosomiasis Control Program (PCE) was implemented in Minas Gerais (MG) in 1984. In 1999, the state started the investigation and control of schistosomiasis in 470 municipalities. The aim of the present paper is to report the evolution of this Program from 1984-2007. The program included a coproscopic survey carried out in the municipalities of known endemic areas using a quantitative method. Positives were treated with praziquantel and given a program of health education. The information for this study was obtained from data collected and stored by the Health State Department. From 2003-2007, 2,643,564 stool examinations resulted in 141,284 positive tests for Schistosoma mansoni (5.3 percent). In the first evaluation after treatment, a decrease in the number of municipalities with prevalence over 10 percent was documented. In one village, selected for a more detailed evaluation, the percentage of positive tests decreased from 14.9 percent in the baseline survey to 5.3 percent after treatment. A reference centre for patients with severe schistosomiasis was created in Belo Horizonte, MG. Based on our findings, we believe that the implementation of PCE in MG is on the right path and in due time these new initiatives will provide desirable results.