Schistosomal liver fibrosis and hepatocellular carcinoma - case series of patients submitted to liver transplantation

ABSTRACT Schistosomiasis affects approximately 207 million people in 76 countries. The association between hepatocellular carcinoma and Schistosoma mansoni infection has been investigated. Studies using animal models suggest that the parasite may accelerate the oncogenic process when combined with other factors, such as hepatitis C virus infection or exposure to a carcinogen. Herein, we report a case series of six hepatocellular carcinoma patients from Northeast Brazil, with negative serology for both hepatitis B and C virus, submitted to liver transplantation, whose explant showed evidence of schistosomal liver fibrosis. Since all patients enrolled in this study were submitted to liver transplantation, we were able to access the whole explanted liver and perform histopathological analysis, which is often not possible in other situations. Although 50% of them showed signs of liver failure, no cirrhosis or any liver disease other than schistosomal fibrosis had been detected. These uncommon findings suggest that Schistosoma mansoni infection might predispose to hepatocellular carcinoma development, regardless of the absence of other risk factors.

Schistosoma mansoni associated glomerulopathy with IgA mesangial deposits: case report / Glomerulopatia esquistossomótica com depósitos mesangiais de IgA: relato de caso

Abstract Introduction: Renal involvement is a severe form of schistosomiasis and occurs in 10% to 15% of patients with the hepatosplenic form of the disease. Nephrotic syndrome is the most common clinical presentation. It is a complication caused by immune complexes (IC), it is rare to appear in the Brazilian context with a immunoglobulin A (IgA) deposits. When installed the renal injury by Schistosoma mansoni, classically presents as membranoproliferative glomerulonephritis (mesangiocapillary) with lobular accentuation. Objective: To report a case of schistosomiasis nephropathy that appeared 7 years after treatment of hepatosplenic schistosomiasis with histologic pattern of mesangial proliferative glomerulonephritis with IgA deposits in mesangium. Clinically developed with progressive decrease of proteinuria with angiotensin receptor blocker (ARB). Method: It was reported a case of a 36 years old patient, brown, with classical sintoms of nephrotic syndrome (proteinuria > 3.5 g/24h, hypoalbuminemia and hypercholesterolemia), however with hepatosplenic schistosomiasis history 7 years ago and portal hypertension. Patient underwent renal biopsy which showed IgA deposits in mesangial, being more intense than immunoglobulin G (IgG), accompanied by C1q and C3, with 4/13 glomeruli sclerotic, standard light mesangial glomerulonephritis renal injury with IgA deposits. Patient began taking ARB with progressive improvement in proteinuria. Conclusion: Patients with glomerulonephritis by schistosoma don't show improvement of disease progression with antiparasitic treatment. However the anti-proteinuric treatment can slow the progression of end stage kidney disease.

Resumo Introdução: O acometimento renal é uma forma grave da esquistossomose e ocorre em 10% a 15% dos pacientes com a forma hepatoesplênica da doença. A síndrome nefrótica é a apresentação clínica mais comum. Trata-se de uma complicação causada por imunocomplexos (IC), sendo rara no contexto brasileiro apresentar-se com depósitos de imunoglobulina A (IgA). Quando instalada a lesão renal pelo Schistosoma mansoni, apresenta-se classicamente como glomerulonefrite membranoproliferativa (mesangiocapilar), com acentuação lobular. Objetivo: Relatar caso de glomerulopatia esquistossomótica que se apresentou 7 anos após tratamento de esquistossomose hepatoesplênica com padrão histológico de glomerulonefrite proliferativa mesangial com depósitos de IgA em mesângio. Clinicamente, evoluiu com diminuição progressiva de proteinúria com bloqueador do receptor de angiotensina (BRA). Método: Foi relatado caso de paciente com 36 anos, parda, com quadro clássico de síndrome nefrótica (proteinúria > 3,5 g/24h, hipoalbuminemia e hipercolesterolemia), no entanto, com histórico de esquistossomose hepatoesplênica há 7 anos e com hipertensão portal. Paciente foi submetida à biópsia renal, que apresentou depósitos de IgA em mesângio, sendo mais intensos que imunoglobulina G (IgG), acompanhados de C1q e C3, com 4/13 glomérulos esclerosados, padrão de lesão renal de glomerulopatia mesangial leve com depósitos de IgA. Paciente iniciou uso de BRA, com melhora progressiva da proteinúria. Conclusão: Pacientes com glomerulopatia por schistosoma não apresentam melhora da progressão da doença com tratamento antiparasitário. Entretanto, o tratamento antiproteinúrico pode retardar a progressão da doença renal crônica terminal.

Cellular immunodeficiency related to chronic dermatophytosis in a patient with Schistosoma mansoni infection: can schistosomiasis induce immunodeficiency?

Abstract: Here, we describe a case of hepatosplenic schistosomiasis that progressed to widespread persistent dermatophytosis. Significant T and B lymphocytopenia was confirmed. T-cell deficit is associated with increased susceptibility to fungal infections of skin and mucous membranes. The accumulation of a large amount of blood cells in the spleen could have played a crucial role in the development of lymphocytopenia in the present case. Alternatively, the schistosomiasis-induced increase in prostaglandin E2 levels could have inhibited the production of interferon-γ, a cytokine fundamental to fungal resistance. This case shows the potential of hepatosplenic schistosomiasis to impair the immune response.

Caput Medusae due to portal hypertension in schistosomiasis mansoni / Cabeza de Medusa debida a la hipertensión portal en esquistosomiasis mansoni

A 62-year-old Brazilian man who lived in endemic areas of tropical diseases had an episode of hematemesis associated with portal hypertension. He used to swim in natural ponds during childhood and developed the hepatosplenic form of schistossomiasis with moderate ascites, in addition to the characteristic features of abdominal Caput Medusae. The aim of the report is highlight the role of chronic liver disease and schistossomiasis

Un hombre natural de Brasil de 62 años de edad que vivía en zonas endémicas de enfermedades tropicales presentó un episodio de hematemesis asociada con hipertensión portal. Frecuentemente se bañaba en los estanques naturales durante la infancia y desarrolló la forma hepatosplénica de la esquistosomiasis con ascitis moderada, además de los rasgos abdominales característicos de la Cabeza de Medusa. El objetivo del informe es poner de relieve el papel de la enfermedad hepática crónica y de la esquistosomiasis

Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

Paciente com cardiopatia chagásica crônica, esquistossomose hepatoesplênica e síndrome da imunodeficiência adquirida: possível resolução espontânea de trombo no ventrículo direito / Patient with chronic Chagas heart disease, hepatosplenic schistosomiasis and acquired immunodeficency syndrome: possible spontaneous resolution of thrombus in the right ventricle

A presença de trombos nas câmaras cardíacas direitas parece aumentar o risco de morte no tromboembolismo. Entretanto, existe discrepância entre a prevalência de trombos intracavitários cardíacos e evidências clínicas de tromboembolismo. Além disso, as características individuais associadas ao elevado risco de mortalidade não estão bem estabelecidas. Este relato descreve o caso de um paciente portador de esquistossomose mansônica, síndrome da imunodeficiência adquirida (SIDA) e doença de Chagas crônica, apresentando grande trombo no ventrículo direito. A evolução foi favorável, sem complicações tromboembólicas e com provável resolução espontânea do trombo.

The presence of right-sided cardiac thrombi seems to increase the risk of death due to thromboembolic events. There is a discrepancy, however, between the prevalence of cardiac thrombus and clinical thromboembolic events. Besides, the individual characteristics associated with a high risk of mortality have not been established. We present here a case report of a patient with mansonic schistosomiasis and acquired immunodeficiency syndrome and chronic Chagas disease, who presents with a large thrombus in the right ventricle. The patient had uneventful evolution without any thromboembolic complications with resolution of right-ventricle thrombus.

Capnografia volumétrica como auxílio diagnóstico não-invasivo no tromboembolismo pulmonar agudo / Volumetric capnography as a noninvasive diagnostic procedure in acute pulmonary thromboembolism

O tromboembolismo pulmonar é uma situação freqüente que pode ser diagnosticada pela cintilografia pulmonar, angiotomografia computadorizada, arteriografia pulmonar e, como método de exclusão, dosagem do dímero-D. Como estes exames nem sempre estão disponíveis, a validação de outros métodos diagnósticos é fundamental. Relata-se o caso de uma paciente com hipertensão pulmonar crônica, agudizada por tromboembolismo pulmonar. Confirmou-se o diagnóstico por cintilografia, angiotomografia computadorizada, arteriografia pulmonar; a dosagem do dímero-D resultou positiva. A capnografia volumétrica associada à gasometria arterial foi realizada na admissão e após o tratamento. As variáveis obtidas foram comparadas com os resultados dos exames de imagem.

Pulmonary thromboembolism is a common condition. Its diagnosis usually requires pulmonary scintigraphy, computed angiotomography, pulmonary arteriography and, in order to rule out other diagnoses, the measurement of D-dimer levels. Due to the fact that these diagnostic methods are not available in most Brazilian hospitals, the validation of other diagnostic techniques is of fundamental importance. We describe a case of a woman with chronic pulmonary hypertension who experienced a pulmonary thromboembolism event. Pulmonary scintigraphy, computed angiotomography and pulmonary arteriography were used in the diagnosis. The D-dimer test result was positive. Volumetric capnography was performed at admission and after treatment. The values obtained were compared with the imaging test results.

Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis

Hepatosplenic schistosomiasis was the first human disease in which the possibility of extensive long standing hepatic fibrosis being degraded and removed has been demonstrated. When such changes occurred, the main signs of portal hypertension (splenomegaly, esophageal varices) progressively disappeared, implying that a profound vascular remodeling was concomitantly occurring. Hepatic vascular alterations associated with advanced schistosomiasis have already been investigated. Obstruction of the intrahepatic portal vein branches, plus marked angiogenesis and compensatory hyperplasia and hypertrophy of the arterial tree are the main changes present. However, there are no data revealing how these vascular changes behave during the process of fibrosis regression. Here the mouse model of pipestem fibrosis was used in an investigation about these vascular alterations during the course of the infection, and also after treatment and cure of the disease. Animals representing the two polar hepatic forms of the infection were included: (1) "isolated granulomas" characterized by isolated periovular granulomas sparsely distributed throughout the hepatica parenchyma; and (2) 'pipestem fibrosis' with periovular granulomas and fibrosis being concentrated within portal spaces, before and after treatment, were studied by means of histological and vascular injection-corrosion techniques. Instances of widespread portal vein obstruction of several types were commonly found in the livers of the untreated animals. These obstructive lesions were soon repaired, and completely disappeared four months following specific treatment of schistosomiasis. Treatment was accomplished by the simultaneous administration of praziquantel and oxamniquine. The most impressive results were revealed by the technique of injection of colored masses into the portal system, followed by corrosion in strong acid. The vascular lesions of non-treated pipestem fibrosis were represented...

Changes of the proximal digestive tract in portal hypertension and their relationship with "Helicobacter pylori", histology and patient's hepatic function

Este trabalho analisa as alteraçöes observadas à endoscopia em pacientes portadores de hipertensäo portal por cirrose e esquistossomose e as correlaciona com os achados histológicos, presença ou näo de H. pylori e funçäo hepática do paciente. Os pacientes cirróticos apresentaram prevalência significativamente mais alta de úlcera péptica, correlaçäo positiva entre presença de gastrite crônica e de H. pylori, assim como relaçäo direta entre o grau das varizes e a presença de gastropatia hipertensiva (GH). Näo houve correlaçäo estatisticamente significativa entre presença de H. pylori e o grupo do paciente, entre a presença de GH e o índice de Child Pagh, nem entre a prevalência de H. pylori e de GH. Finalmente, näo houve diferença significativa na prevalência de gastrite crônica entre os grupos de pacientes

Schistosomiasis: predisposing cause for the formation of hepatic abscesses? : case report

Paciente adulto, natural de regiao endemica para esquistossomose e portador cronico da doenca, apresenta queixa de febre ha sete dias, associada a ictericia e dor lombar em regiao direita. Os exames radiologicos mostraram abscessos hepaticos piogenicos multiplos, cuja causa predisponente e conhecida, segundo trabalhos da literatura, em 100 por cento dos casos. Atraves de parametros clinicos, laboratoriais e radiologicos todas as etiologias classicas foram afastadas. Sabe-se que a esquistossomose pode provocar, como complicacao, a pileflebite, alem de depressao imunologica e reacao granulomatosa com necrose lobular central e maior risco de infeccao. Os autores deste relato de caso sugerem ser a esquistossomose, na sua forma cronica, causa predisponente para formacao de abscessos hepaticos piogenicos multiplos, principalmente em regioes endemicas.

Chronic glomerulonephritis associated with hepatosplenic Schistosomiasis mansoni

Numa série de 36 casos de doença renal em portadores de esquistossomose hépato-esplênica, os tipos histológicos de glomerulonefrite encontrados foram os seguintes: mesângio-capilar (33,2%), proliferativa mensagial (25,0%), esclerose glomerular focal (16,7%) e glomerulonefrite esclerosante (8,3%). Quando estes tipos e números foram comparados com aqueles obtidos de um grupo contrôle de 36 casos de glomerulonefrite sem associaçäo com a esquistossomose hépato-esplênica, näo foram verificadas diferenças estatísticamente significantes, a näo ser em relaçäo à glomerulonefrite proliferativa endocapilar que apareceu muito mais frequentemente no grupo contrôle. Assim sendo, a idéia de que a glomerulonefrite mesângio-capilar está especificamente associada com a esquistossomose näo se consubstanciou. Todavia, quando se consideram juntos os dois grupos de gomerulonefrite com envolvimento predominantemente mesangial (mesângio-capilar e proliferativa mensagial), há uma nítida predominância dos mesmos nos casos associados com a esquistossomose hépato esplênica. Este dado pode estar ligado à existência de imuno-complexos de grande peso molecular, os quais tendem a se depositar no mesângio, como parece ser o caso com as glomerulonefrites associadas com infecçöes parasitárias em geral