Dataset Information

Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis.

ABSTRACT:

Background

Schistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n?=?55) correlate with the severity of their periportal fibrosis.

Methodology/principal findings

Blood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR). The blood coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa (ATIIa), plasminogen activator inhibitor 1 (PAI-1) and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n?=?29), including raised serum transaminases (p<0.001) and lower levels of albumin (p?=?0.0156). Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001) and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001). Additionally, patients with more advanced fibrosis (n?=?38) had lower levels of protein C compared to those with only central fibrosis (p?=?0.0124). The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001), and D-dimer levels 2.2 times higher (p<0.001) with 13 of the 55 patients having levels above the cut-off.

Conclusion/significance

This study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and advanced periportal fibrosis have hyperfibrinolysis, as judged by excessive levels of D-dimer, which may predispose them to gastrointestinal bleeding.

SUBMITTER: Leite LA

PROVIDER: S-EPMC3715409 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis.

Leite Luiz Arthur Calheiros LA Pimenta Filho Adenor Almeida AA Martins da Fonseca Caíque Silveira CS Santana dos Santos Bianka B Ferreira Rita de Cássia dos Santos Rde C Montenegro Silvia Maria Lucena SM Lopes Edmundo Pessoa EP Domingues Ana Lúcia Coutinho AL Owen James Stuart JS Lima Vera Lúcia de Menezes VL

PLoS neglected tropical diseases 20130718 7

<h4>Background</h4>Schistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55) correlate with the severity of their periportal fibrosis.<h4>Methodology/principal find ...[more]

PMID: 23875049

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Project description:Schistosomiasis is a parasitic disease that affects about 166 million people around the world. It is estimated that 5%-10% of individuals with schistosomiasis develop severe forms of the disease, which are characterized by pulmonary hypertension, ascites, periportal fibrosis, and other significant complications. The chronic phase of the disease is associated with a Th2 type immune response, but evidence also suggests there are roles for Th1 and Th17 in the development of severe disease. The aim of this study was to evaluate the CD4+ T lymphocyte profile of patients with different degrees of periportal fibrosis secondary to schistosomiasis. These individuals had been treated for schistosomiasis, but since they live in a S. mansoni endemic area, they are at risk of reinfection. They were evaluated in relation to the degree of periportal fibrosis and classified into three groups: without fibrosis or with incipient fibrosis (WF/IFNE), n=12, possible periportal fibrosis/periportal fibrosis, n=13, and advanced periportal fibrosis/advanced periportal fibrosis with portal hypertension, n=4. We observed in the group without fibrosis a balance between the low expression of Th2 cytokines and high expression of T reg cells. As has already been described in the literature, we found an increase of the Th2 cytokines IL-4, IL-5, and IL-13 in the group with periportal fibrosis. In addition, this group showed higher expression of IL-17 and IL-10 but lower IL-10/IL-13 ratio than patients in the WF/IFNE group. Cells from individuals who present any level of fibrosis expressed more TGF-β compared to the WF/IFNE group and a positive correlation with left lobe enlargement and portal vein wall thickness. There was a negative correlation between IL-17 and the thickness of the portal vein wall, but more studies are necessary in order to explore the possible protective role of this cytokine. Despite the fibrosis group having presented a higher expression of pro-fibrotic molecules compared to WF/IFNE patients, it seems there is a regulation through IL-10 and T reg cells that is able to maintain the low morbidity of this group.

Project description:BackgroundHepatosplenic schistosomiasis (HSS) is a disease caused by chronic infection with Schistosma spp. parasites residing in the mesenteric plexus; portal hypertension causing gastrointestinal bleeding is the most dangerous complication of this condition. HSS requires complex clinical management, but no specific guidelines exist. We aimed to provide a comprehensive picture of consolidated findings and knowledge gaps on the diagnosis and treatment of HSS.Methodology/principal findingsWe reviewed relevant original publications including patients with HSS with no coinfections, published in the past 40 years, identified through MEDLINE and EMBASE databases. Treatment with praziquantel and HSS-associated pulmonary hypertension were not investigated. Of the included 60 publications, 13 focused on diagnostic aspects, 45 on therapeutic aspects, and 2 on both aspects. Results were summarized using effect direction plots. The most common diagnostic approaches to stratify patients based on the risk of variceal bleeding included the use of ultrasonography and platelet counts; on the contrary, evaluation and use of noninvasive tools to guide the choice of therapeutic interventions are lacking. Publications on therapeutic aspects included treatment with beta-blockers, local management of esophageal varices, surgical procedures, and transjugular intrahepatic portosystemic shunt. Overall, treatment approaches and measured outcomes were heterogeneous, and data on interventions for primary prevention of gastrointestinal bleeding and on the long-term follow-up after interventions were lacking.ConclusionsMost interventions have been developed on the basis of individual groups' experiences and almost never rigorously compared; furthermore, there is a lack of data regarding which parameters can guide the choice of intervention. These results highlight a dramatic need for the implementation of rigorous prospective studies with long-term follow-up in different settings to fill such fundamental gaps, still present for a disease affecting millions of patients worldwide.

Project description:BackgroundSevere hepatosplenic complications arise in patients with chronic Schistosoma mansoni infection after heavy exposure to disease agents in endemic areas. These complications are rarely reported and, hence, underestimated.Case presentationWe report on eight patients with severe morbidity associated with S. mansoni infection in Ituri Province, northeastern Democratic Republic of Congo (DRC). The patients were identified during a community-based survey in 2017; one patient was seen at the district hospital. After taking the patients' history, a clinical examination and an abdominal ultrasonographical examination were performed. S. mansoni infection was diagnosed in fecal (Kato-Katz technique) and urine (point-of-case circulating cathodic antigen test) samples. These eight patients with severe intestinal and hepatosplenic complications were identified from four villages with high S. mansoni infection prevalence and related morbidity. The patients' ages ranged from 19 to 57 years; four patients were women. Three patients reported hematemesis. Two patients were severely anemic. All patients reported non-specific abdominal symptoms, such as diarrhea (six patients), abdominal pain (seven patients), and blood in the stool (five patients), as well as weight loss (two patients). Abdominal ultrasonography revealed ascites in four patients. All patients had portal hypertension with hepatomegaly (seven patients) or splenomegaly (five patients). Of the six patients with a discernable liver parenchyma pattern, five displayed pattern F and three patient displayed pattern E. Liver parenchyma was not visible for two patients with severe ascites. An S. mansoni infection was confirmed in six patients, with infection intensity ranging from light to heavy. All S. mansoni positive patients were treated with praziquantel (40 mg/kg body weight) and referred to the district hospital for follow-up. One patient with severe ascites died two weeks after we saw her. Due to security and accessibility reasons, the villages could not be visited again and the patients were lost to follow-up.ConclusionsOur observations of patients with severe schistosomiasis document the severe degree of endemicity of S. mansoni in the province and suggest an urgent need for adequate schistosomiasis control measures that target vulnerable population groups and address severe complications.

Project description:BackgroundSchistosomiasis is endemic to several parts of the world. Among the species that affect humans, Schistosoma mansoni is one of the most common causes of illness. In regions where schistosomiasis mansoni is endemic, reinfection is responsible for the emergence of hepatosplenic schistosomiasis (HSS) with portal hypertension in about 10% of infected individuals. Regardless of its etiology, portal hypertension may bring about the formation of arteriovenous fistulas and pulmonary vascular dilation, thus constituting a pulmonary shunt and its presence has been associated with the occurrence of neurological complications. The objective of this study was to identify pulmonary shunt using TTCE in patients with HSS and esophageal varices, and to compare the abdominal ultrasound and endoscopy findings among patients with and without pulmonary shunt.Methodology/principal findingsIn this case series, a total of 461 patients with schistosomiasis mansoni were prospectively evaluated using abdominal ultrasound and endoscopy and 71 presented with HSS with esophageal varices. Fifty seven patients remained in the final analysis. The mean age of the patients was 55 ± 14 years, and 65% were female. Pulmonary shunts were observed in 19 (33.3%) patients. On comparing the groups with and without pulmonary shunt, no significant differences were observed in relation to the abdominal ultrasound and endoscopic findings. When comparing the two subgroups with pulmonary shunts (grade 1 vs grades 2 and 3), it was observed that the subgroup with shunt grades 2 and 3 presented with a significantly higher frequency of an enlarged splenic vein diameter (>0.9 cm), and an advanced pattern of periportal hepatic fibrosis (P = 0.041 and P = 0.005, respectively). None of the patients with pulmonary shunts had severe neurological complications.Conclusions/significanceOur findings suggest that in HSS with esophageal varices the pulmonary shunts may be present in higher grades and that in this condition it was associated with ultrasound findings compatible with advanced HSS.

Project description:BackgroundSymptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection.Methodology/principal findingsSerum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7-11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells.Conclusions/significanceS. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.

Dataset Information

Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis.

Background

Methodology/principal findings

Conclusion/significance

Publications

Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis.

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