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1
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Ahmed SAA, Gad SEM, Eida OM, Makhlouf LM. Anti-fibrotic Effect of Oral Versus Intraperitoneal Administration of Gold Nanoparticles in Hepatic Schistosoma mansoni-Infected Mice. Acta Parasitol 2024; 69:190-202. [PMID: 37964174 PMCID: PMC11001733 DOI: 10.1007/s11686-023-00730-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 10/12/2023] [Indexed: 11/16/2023]
Abstract
BACKGROUND Schistosomiasis significantly impacts public health, as it causes severe morbidity. Infections caused by Schistosoma mansoni (S. mansoni) can be treated with gold nanoparticles (AuNPs). This study aims to determine the most effective route of AuNPs administration and the magnitude of its anti-fibrotic effect. METHODS In the five groups' in vivo assay design, AuNPs were administered intraperitoneally (1 mg/kg) and orally (1 mg/100 g) to S. mansoni-infected mice. Biochemical parameters (serum levels of albumin and liver enzymes alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. The histological changes of the liver in distinct groups were evaluated using Hematoxylin and Eosin, Masson's trichrome, and immunohistochemical stains. RESULTS Infection with S. mansoni was associated with substantial changes in the histological architecture of liver tissue and abnormal levels of hepatic function tests (albumin, AST, and ALT). Schistosoma infected hepatocytes exhibited an abnormal microscopic morphology, granuloma formation and aggressive fibrosis. AuNPs restored the liver histological architecture with a highly significant anti-fibrotic effect and significantly corrected hepatic function test levels. Intraperitoneal administration of AuNPs resulted in the most significant anti-fibrotic effect against hepatic S. mansoni infection as observed in all histological sections with Masson's trichrome being the best stain to represent this fact. CONCLUSION For treating S. mansoni-induced chronic liver fibrosis, intraperitoneal administration of AuNPs is a successful and effective route of administration that can be recommended.
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Affiliation(s)
| | - Samer Eid Mohamed Gad
- Department of Parasitology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt
| | - Omima Mohamed Eida
- Department of Parasitology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt
| | - Laila Mohamed Makhlouf
- Department of Parasitology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt
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2
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Liu Y, Zhang P, Li J, Li H, Zhou C, Zhang Y, Ming Y. Association between serum lipid profile and liver fibrosis in patients infected with Schistosoma japonicum. Parasit Vectors 2022; 15:268. [PMID: 35906693 PMCID: PMC9336000 DOI: 10.1186/s13071-022-05359-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 06/10/2022] [Indexed: 12/15/2022] Open
Abstract
Background Liver fibrosis is thought to have a close relationship with lipid profile. The possible association between lipids and liver fibrosis of different etiologies has been widely explored. However, the association between lipids and liver fibrosis in patients infected with Schistosoma japonicum remains unclear. In the present study we undertook a preliminary exploration of the association between lipid profile and liver fibrosis, and developed a new predictive index for liver fibrosis in S. japonicum-infected patients. Methods A total of 1503 patients diagnosed with S. japonicum at Xiangyue Hospital, China were enrolled in this retrospective study. The patients were divided into two groups, i.e., those with and those without liver fibrosis, by two experienced schistosomiasis specialists, according to the results of liver ultrasound examination. Demographic, clinical, and laboratory data were collected. Multivariable logistic models were used to estimate the independent associations between lipid profile and liver fibrosis. Receiver operating characteristic (ROC) curves were used to assess the discriminative ability of the new index in predicting liver fibrosis in patients with schistosomiasis. Results Logistic regression analysis showed that high-density lipoprotein (HDL) [adjusted odds ratio (aOR), 95% confidence interval (CI) 7.334, 5.051–10.649; P < 0.001], low-density lipoprotein (LDL) (aOR, 95% CI 0.434, 0.370–0.509; P < 0.001), hemoglobin (HB) (aOR, 95% CI 0.979, 0.971–0.987; P < 0.001) and platelets (PLT) (aOR, 95% CI 0.996, 0.994–0.999; P < 0.001) were independently associated with liver fibrosis in patients with schistosomiasis. ROC analysis indicated that the combination of HDL, LDL and HB levels [(HDL × 100)/(LDL × HB)] had a higher area under the ROC curve (AUC = 0.773), and thus may better predict liver fibrosis than the aspartate transaminase-to-platelet ratio index (AUC = 0.608) and fibrosis index based on four factors (AUC = 0.624). Conclusions To the best of our knowledge, this is the first study to report that HDL, LDL, HB and PLT levels are independently associated with liver fibrosis in patients with schistosomiasis. (HDL × 100)/(LDL × HB) outperformed the aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors in terms of ROC, and thus could be a new predictive index for liver fibrosis. These findings may help clinicians to more easily and effectively diagnose liver fibrosis in patients with schistosomiasis. Graphical abstract ![]()
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Affiliation(s)
- Yang Liu
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China
| | - PengPeng Zhang
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China.,Engineering and Technology Research Center for Transplantation Medicine, National Health Commission, Changsha, 410013, China
| | - JunHui Li
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China.,Engineering and Technology Research Center for Transplantation Medicine, National Health Commission, Changsha, 410013, China
| | - Hao Li
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China
| | - Chen Zhou
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China
| | - Yu Zhang
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China
| | - YingZi Ming
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China. .,Engineering and Technology Research Center for Transplantation Medicine, National Health Commission, Changsha, 410013, China.
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3
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Liao MJ, Li J, Dang W, Chen DB, Qin WY, Chen P, Zhao BG, Ren LY, Xu TF, Chen HS, Liao WJ. Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China. World J Gastroenterol 2022; 28:3503-3513. [PMID: 36158257 PMCID: PMC9346453 DOI: 10.3748/wjg.v28.i27.3503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/23/2022] [Accepted: 06/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Noninvasive, practical, and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.
AIM To develop a precise noninvasive test to stage liver fibrosis and cirrhosis.
METHODS With liver biopsy as the gold standard, we established a new index, [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)/platelet (109/L) (AGPR)], to predict liver fibrosis and cirrhosis. In addition, we compared the area under the receiver operating characteristic curve (AUROC) of AGPR, gamma-glutamyl transpeptidase to platelet ratio, aspartate transaminase to platelet ratio index, and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis.
RESULTS Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage (P < 0.001). In the training cohort, the AUROC of AGPR was 0.83 (95%CI: 0.78-0.87) for predicting fibrosis (≥ F2), 0.84 (95%CI: 0.79-0.88) for predicting extensive fibrosis (≥ F3), and 0.87 (95%CI: 0.83-0.91) for predicting cirrhosis (F4). In the validation cohort, the AUROCs of AGPR to predict ≥ F2, ≥ F3 and F4 were 0.83 (95%CI: 0.77-0.88), 0.83 (95%CI: 0.77-0.89), and 0.84 (95%CI: 0.78-0.89), respectively.
CONCLUSION The AGPR index should become a new, simple, accurate, and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.
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Affiliation(s)
- Min-Jun Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Jun Li
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
- Genetics and Precision Medicine Laboratory, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Wei Dang
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Dong-Bo Chen
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People’s Hospital, Beijing 100044, China
| | - Wan-Ying Qin
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Pu Chen
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People’s Hospital, Beijing 100044, China
| | - Bi-Geng Zhao
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Li-Ying Ren
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Ting-Feng Xu
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Hong-Song Chen
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People’s Hospital, Beijing 100044, China
| | - Wei-Jia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
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4
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Santos JC, Pereira CLD, Domingues ALC, Lopes EP. Noninvasive diagnosis of periportal fibrosis in schistosomiasis mansoni: A comprehensive review. World J Hepatol 2022; 14:696-707. [PMID: 35646262 PMCID: PMC9099109 DOI: 10.4254/wjh.v14.i4.696] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 09/14/2021] [Accepted: 03/14/2022] [Indexed: 02/06/2023] Open
Abstract
Schistosomiasis mansoni is a neglected disease and key public health problem, mainly due to its high prevalence, the scarcity of public policies, and the severity of some clinical forms. Periportal fibrosis (PPF) is the commonest complication of chronic schistosomiasis mansoni and its diagnosis requires different techniques. Even though wedge biopsy of the liver is considered the gold standard, it is not justified in non-surgical patients, and percutaneous liver biopsy may be informative but does not have sufficient sensitivity. Noninvasive PPF tests mostly include biological (serum biomarkers or combined scores) or physical assessments (imaging assessment of fibrosis pattern or tissue stiffness). Moreover, imaging techniques, such as ultrasound, computed tomography, magnetic resonance imaging, and elastography are applied not only to support the diagnosis of schistosomiasis, but also to assess and detect signs of portal hypertension and organ damage due to chronic schistosomiasis. A combination between a comprehensive history and physical examination with biomarkers for liver fibrosis and imaging methods seems to offer the best approach for evaluating these patients. In addition, understanding their strengths and limitations will allow a more accurate interpretation in the clinical context and can lead to greater accuracy in estimating the degree of fibrosis in patients with Schistosomiasis mansoni (S. mansoni) infection. This review will discuss the different noninvasive methods that are currently available for the evaluation of PPF in S. mansoni infection, and their application, advantages, and limitations in clinical practice.
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Affiliation(s)
- Joelma Carvalho Santos
- Postgraduate Program in Tropical Medicine, Center of Health Sciences, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
| | - Caroline Louise Diniz Pereira
- Postgraduate Program in Tropical Medicine, Center of Health Sciences, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
| | - Ana Lúcia Coutinho Domingues
- Postgraduate Program in Tropical Medicine, Center of Health Sciences, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
- Gastroenterology Division, Department of Internal Medicine of Center of Health Sciences, Hospital das Clínicas - Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
| | - Edmundo Pessoa Lopes
- Postgraduate Program in Tropical Medicine, Center of Health Sciences, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
- Gastroenterology Division, Department of Internal Medicine of Center of Health Sciences, Hospital das Clínicas - Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil.
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5
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Franco KGS, de Amorim FJR, Santos MA, Rollemberg CVV, de Oliveira FA, França AVC, Santos CNO, Magalhães LS, Cazzaniga RA, de Lima FS, Benevides L, Carregaro V, Silva JS, Brito HLDF, Fernandes DA, da Silva ÂM, de Almeida RP, Bezerra-Santos M, de Jesus AR. Association of IL-9, IL-10, and IL-17 Cytokines With Hepatic Fibrosis in Human Schistosoma mansoni Infection. Front Immunol 2021; 12:779534. [PMID: 34970264 DOI: 10.3389/fimmu.2021.779534]] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 11/15/2021] [Indexed: 02/05/2023] Open
Abstract
This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP-10 μg/ml) or egg (SEA-10 μg/ml) antigens or purified protein derivative of turberculin (PPD-10 μg/ml) or phytohemagglutinin (PHA-1 μg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17, IL10, and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.
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Affiliation(s)
- Karine Garcez Schuster Franco
- Image and Graphic Methods Unit, University Hospital, Federal Sergipe University, Aracaju, Brazil
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
| | - Fabio Jorge Ramalho de Amorim
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Mário Adriano Santos
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
| | - Carla Virgínia Vieira Rollemberg
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Fabricia Alvisi de Oliveira
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Alex Vianey Callado França
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
- Hepatology Service, University Hospital, Federal University of Sergipe, Aracaju, Brazil
| | - Camilla Natália Oliveira Santos
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Lucas Sousa Magalhães
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Rodrigo Anselmo Cazzaniga
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | | | - Luciana Benevides
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Vanessa Carregaro
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - João Santana Silva
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | | | | | - Ângela Maria da Silva
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
- Infectology Service, University Hospital, Federal University of Sergipe, Sergipe, Brazil
| | - Roque Pacheco de Almeida
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
- Immunology Institute of Investigation (III), National Institute of Science and Technology (INCT), Brazilian Research and Technology Council (CNPq), São Paulo, Brazil
| | - Márcio Bezerra-Santos
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
- Department of Morphology, Federal University of Sergipe, São Cristóvão, Brazil
| | - Amélia Ribeiro de Jesus
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
- Immunology Institute of Investigation (III), National Institute of Science and Technology (INCT), Brazilian Research and Technology Council (CNPq), São Paulo, Brazil
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6
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Franco KGS, de Amorim FJR, Santos MA, Rollemberg CVV, de Oliveira FA, França AVC, Santos CNO, Magalhães LS, Cazzaniga RA, de Lima FS, Benevides L, Carregaro V, Silva JS, Brito HLDF, Fernandes DA, da Silva ÂM, de Almeida RP, Bezerra-Santos M, de Jesus AR. Association of IL-9, IL-10, and IL-17 Cytokines With Hepatic Fibrosis in Human Schistosoma mansoni Infection. Front Immunol 2021; 12:779534. [PMID: 34970264 PMCID: PMC8712476 DOI: 10.3389/fimmu.2021.779534] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 11/15/2021] [Indexed: 02/05/2023] Open
Abstract
This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP-10 μg/ml) or egg (SEA-10 μg/ml) antigens or purified protein derivative of turberculin (PPD-10 μg/ml) or phytohemagglutinin (PHA-1 μg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17, IL10, and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.
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Affiliation(s)
- Karine Garcez Schuster Franco
- Image and Graphic Methods Unit, University Hospital, Federal Sergipe University, Aracaju, Brazil
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
| | - Fabio Jorge Ramalho de Amorim
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Mário Adriano Santos
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
| | - Carla Virgínia Vieira Rollemberg
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Fabricia Alvisi de Oliveira
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Alex Vianey Callado França
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
- Hepatology Service, University Hospital, Federal University of Sergipe, Aracaju, Brazil
| | - Camilla Natália Oliveira Santos
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Lucas Sousa Magalhães
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | - Rodrigo Anselmo Cazzaniga
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
| | | | - Luciana Benevides
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Vanessa Carregaro
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - João Santana Silva
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | | | | | - Ângela Maria da Silva
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
- Infectology Service, University Hospital, Federal University of Sergipe, Sergipe, Brazil
| | - Roque Pacheco de Almeida
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
- Immunology Institute of Investigation (III), National Institute of Science and Technology (INCT), Brazilian Research and Technology Council (CNPq), São Paulo, Brazil
| | - Márcio Bezerra-Santos
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
- Department of Morphology, Federal University of Sergipe, São Cristóvão, Brazil
| | - Amélia Ribeiro de Jesus
- Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil
- Laboratory of Molecular Biology, University Hospital, Federal Sergipe University, Aracaju, Brazil
- Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil
- Immunology Institute of Investigation (III), National Institute of Science and Technology (INCT), Brazilian Research and Technology Council (CNPq), São Paulo, Brazil
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Hashim A, Berzigotti A. Noninvasive Assessment of Schistosoma-Related Periportal Fibrosis. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:2273-2287. [PMID: 33448437 DOI: 10.1002/jum.15623] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 12/18/2020] [Accepted: 12/22/2020] [Indexed: 06/12/2023]
Abstract
Schistosomiasis affects nearly 250 million individuals in the world. Hepatosplenic schistosomiasis (HSS) results in periportal fibrosis (PPF) and portal hypertension (pHTN). Ultrasound has been extensively used for the diagnosis of Schistosoma-related PPF and a number of staging methods have been validated for this purpose such as Strickland classification and Niamey protocol. Nevertheless, the application of noninvasive techniques, particularly elastography modalities, has not been well explored. In this review, we describe the various noninvasive diagnostic tools for assessment of Schistosoma-related PPF including US parameters, serum biomarkers, and US-based elastography techniques. While elastography techniques have demonstrated value in the evaluation of HSS, the evidence remains limited with most studies recruiting a small number of patients. Longitudinal studies with larger sample size are required in order to devise robust criteria to accurately assess the performance of noninvasive techniques in the prediction of both regression and progression of the degree of PPF and identify their cost-effectiveness in community screening.
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Affiliation(s)
- Ahmed Hashim
- Hepatology Department, Royal Free Hospital, London, UK
| | - Annalisa Berzigotti
- University of Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland
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Zhao L, Li L, Ren H, Zou Y, Zhang R, Wang S, Xu H, Zhang J, Liu F. Association between serum alkaline phosphatase and renal outcome in patients with type 2 diabetes mellitus. Ren Fail 2021; 42:818-828. [PMID: 32781868 PMCID: PMC7472471 DOI: 10.1080/0886022x.2020.1804402] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
This retrospective study included 299 patients with type 2 diabetes mellitus and biopsy-confirmed diabetic nephropathy (DN) to investigate the prognostic value of alkaline phosphatase (ALP) for renal outcome. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for the serum ALP level on renal outcome, which was defined as end-stage renal disease (ESRD) or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. The median baseline ALP was 80 IU/L with an interquartile range of 64–97 IU/L. Serum ALP was negatively associated with eGFR but positively associated with proteinuria and renal interstitial fibrosis. During a median follow-up period of 23 months, ESRD or a 50% declined in the eGFR occurred in 156 (52.2%) patients. The highest quartile of ALP was significantly associated with poor renal outcome, as defined above (HR 2.38, 95% confidence interval [CI] 1.09–5.17), when adjusted for sociodemographics, baseline eGFR, proteinuria, liver function parameters, parathyroid hormone levels, and renal pathological findings. Each standard deviation higher in the natural log-transformed ALP was associated with a 25% increased risk for poor renal outcome. Additionally, there was a graded increase in the risk for poor renal outcome with higher ALP in patients with nephrotic-range proteinuria. However, no significant associations were observed between serum ALP levels and renal outcome in patients with non-nephrotic-range proteinuria. In conclusion, an elevated ALP level was independently associated with poor renal outcome in patients with type 2 diabetes mellitus and nephrotic-range proteinuria after multivariate adjustment.
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Affiliation(s)
- Lijun Zhao
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Lin Li
- Division of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Honghong Ren
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Yutong Zou
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Rui Zhang
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Shanshan Wang
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Huan Xu
- Division of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jie Zhang
- Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, Chengdu, Sichuan, China
| | - Fang Liu
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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Gunda DW, Mtui EF, Manyiri PM, Majinge DC, Kilonzo SB, Mazigo HD, Kidenya BR. Schistosoma mansoni-related periportal fibrosis; can we use APRI and PSDR levels in the real-time selection of patients for targeted endoscopy in a resource-limited setting? A case-control study. BMC Gastroenterol 2021; 21:219. [PMID: 33985430 PMCID: PMC8117578 DOI: 10.1186/s12876-021-01802-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 05/03/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Schistosoma mansoni related hepatic fibrosis is usually associated with hemodynamic alteration with increased mortality due to bleeding varices. The diagnosis of varices before bleeding imposes a big challenge in resource-limited countries using endoscopy. Published evidence on the utility of non-invasive clinical tools in predicting the presence of varices among patients with S. mansoni related periportal fibrosis is still inadequate including Aspartate to platelet ratio index (APRI) and Platelet to splenic diameter ratio (PSDR) levels. This study describes the determinants of portal varices and assesses the potential utility of the APRI and PSDR level in the discrimination of portal varices among patients with S. mansoni related periportal fibrosis (PPF). METHODS A case-control study using cross-sectional data was done among patients with Schistosoma mansoni related periportal fibrosis at Bugando Medical Centre, in Mwanza Tanzania. The derivation cohort included patients enrolled between 2015 and 2019 and the validation cohort included patients enrolled from 2019 till March 2021. Socio-demographic, laboratory, ultrasound, and upper digestive endoscopic information were analyzed using STATA 13. The prevalence and determinants of varices were determined by logistic regression. The sensitivity and specificity of independent factors were determined to assess their utility in discriminating the presence of portal varices in patients with PPF. RESULTS In total, 250 patients were included in the derivation cohort, 109 (43.6%; 95% CI 37.3-49.9) of them had varices. The odds of having varices were independently increased among patients with higher APRI levels than 1.51, (AOR: 5.8; 95% CI 3.1-11.1; p < 0.001) and PSDR levels that were lower than 5700 (AOR: 5.9; 95% CI 3.2-11.2; p < 0.001). Both APRI and PSDR levels had significantly high sensitivity and specificity in predicting the presence of esophageal varices. However, the combined values of APRI and PSDR had higher specificity than any of the two markers. Of the 200 patients in the validation cohort 94 (47.0%; 95% CI 40.0-54.2) had varices, the discriminative power of the final model and the predictive ability of both APRI, PSDR, and APRI-PSDR combined levels were highly maintained. CONCLUSIONS This study indicates that varices are a common encounter among patients with S. mansoni related periportal fibrosis and it is independently associated with higher APRI and lower PSDR levels suggesting that these tools are potential discriminators of varices in this subgroup of patients. The reproducibility of these results should further be assessed longitudinally as potential non-invasive tools in selecting patients at high risk of having esophageal varices who could benefit from the targeted endoscopic intervention in a resource-limited setting like ours.
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Affiliation(s)
- Daniel W. Gunda
- Department of Internal Medicine, Catholic University of Health and Allied Sciences, 1464 Mwanza, Tanzania
- Department of Internal Medicine, Bugando Medical Centre, 1370 Mwanza, Tanzania
| | - Elizabeth F. Mtui
- Department of Internal Medicine, Catholic University of Health and Allied Sciences, 1464 Mwanza, Tanzania
| | - Paulina M. Manyiri
- Department of Internal Medicine, Bugando Medical Centre, 1370 Mwanza, Tanzania
| | - David C. Majinge
- Department of Internal Medicine, Bugando Medical Centre, 1370 Mwanza, Tanzania
| | - Semvua B. Kilonzo
- Department of Internal Medicine, Catholic University of Health and Allied Sciences, 1464 Mwanza, Tanzania
- Department of Internal Medicine, Bugando Medical Centre, 1370 Mwanza, Tanzania
| | - Humphrey D. Mazigo
- Department of Parasitology, Catholic University of Health and Allied Sciences, 1464 Mwanza, Tanzania
| | - Benson R. Kidenya
- Department of Biochemistry and Molecular Biology, Catholic University of Health and Allied Sciences, 1464 Mwanza, Tanzania
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10
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Pereira CLD, Santos JC, Arruda RM, Rodrigues ML, Siqueira ES, Lemos RS, Batista AD, Domingues ALC, Lopes EP. Evaluation of Schistosomiasis Mansoni Morbidity by Hepatic and Splenic Elastography. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:1235-1243. [PMID: 33618959 DOI: 10.1016/j.ultrasmedbio.2021.01.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 01/14/2021] [Accepted: 01/21/2021] [Indexed: 12/13/2022]
Abstract
In patients with Mansoni schistosomiasis, it is fundamental to evaluate the disease morbidity, which is reflected by the severity of periportal fibrosis (PPF) and parameters of portal hypertension, as analyzed by ultrasonography (US). This study aimed to evaluate the morbidity of schistosomiasis by hepatic and splenic point shear-wave elastography (pSWE) and relate this to US parameters. The PPF pattern, the diameter of the portal and splenic veins and the size of the spleen were evaluated by US. Then, liver and spleen pSWEs were assessed in 74 patients using the same equipment. As the PPF pattern progressed, the splenic pSWE values significantly increased. Significant correlations between splenic pSWE, the longitudinal and transverse lengths of the spleen and the diameters of the portal and splenic veins were observed. These findings, however, were not observed through hepatic pSWE. In conclusion, the splenic pSWE has the potential for assessing morbidity in schistosomiasis mansoni.
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Affiliation(s)
- Caroline Louise Diniz Pereira
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Brazil
| | - Joelma Carvalho Santos
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Brazil
| | | | - Milena Lima Rodrigues
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Brazil
| | | | - Roberto Souza Lemos
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Brazil
| | | | - Ana Lúcia Coutinho Domingues
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Brazil; Gastroenterology Service, Hospital das Clínicas, UFPE, Recife, Brazil
| | - Edmundo Pessoa Lopes
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Brazil; Gastroenterology Service, Hospital das Clínicas, UFPE, Recife, Brazil.
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11
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Barreto AVMS, Domingues ALC, Diniz GTN, Cavalcanti AMS, Lopes EP, Montenegro SML, Morais CNL. The Coutinho index as a simple tool for screening patients with advanced forms of Schistosomiasis mansoni: a validation study. Trans R Soc Trop Med Hyg 2021; 116:19-25. [PMID: 33728455 DOI: 10.1093/trstmh/trab040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 01/07/2021] [Accepted: 02/24/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Periportal fibrosis (PPF) is the major pathological consequence of Schistosoma mansoni infection. The Coutinho index-the alkaline phosphatase (ALP) to platelet ratio ([ALP/upper limit of normality {ULN}]/platelet count [106/L] x 100)-was validated. Validation consisted of modest laboratory tests to predict advanced PPF. METHODS A total of 378 individuals from an endemic area of Brazil with a previous history of the disease and/or a positive parasitological examination were evaluated. We used ultrasound examination as the gold standard for classification of the PPF pattern and measured the biological markers of the index. RESULTS Forty-one individuals (10.8%) without PPF, 291 (77%) with moderate PPF and 46 (12.2%) with advanced PPF, were identified. ALP and platelet count were used for the index. The cut-off point ≥0.228 predicted the presence of fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.56, sensitivity of 68.6% and specificity of 46.3%. There was an absence of PPF in 46.3% of individuals without fibrosis and the presence of PPF in 68.5% of cases with moderate and advanced ultrasound fibrosis. The identification of advanced fibrosis with a cut-off point ≥0.316 revealed an AUROC curve of 0.70, sensitivity of 67.4% and specificity of 68.3%, thus confirming the advanced phase in 65.2% of cases compared with ultrasound. CONCLUSION The Coutinho index was able to predict advanced PPF in most individuals. It is valid as a new tool, uses routine laboratory tests and therefore is more accessible for screening patients with a severe form of the disease in endemic areas.
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Affiliation(s)
- Ana V M S Barreto
- Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife-Pernambuco, 50670-420, Brasil
| | - Ana L C Domingues
- Centro de Ciências Médicas, Universidade Federal de Pernambuco, Recife-Pernambuco, 50670-901, Brasil
| | - George T N Diniz
- Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife-Pernambuco, 50670-420, Brasil
| | - Ana M S Cavalcanti
- Laboratório Central de Saúde Pública, Secretaria Estadual de Saúde, Recife-Pernambuco, 52171-011, Brasil
| | - Edmundo P Lopes
- Centro de Ciências Médicas, Universidade Federal de Pernambuco, Recife-Pernambuco, 50670-901, Brasil
| | - Silvia M L Montenegro
- Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife-Pernambuco, 50670-420, Brasil
| | - Clarice N L Morais
- Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife-Pernambuco, 50670-420, Brasil
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12
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Mewamba EM, Nyangiri OA, Noyes HA, Egesa M, Matovu E, Simo G. The Genetics of Human Schistosomiasis Infection Intensity and Liver Disease: A Review. Front Immunol 2021; 12:613468. [PMID: 33659002 PMCID: PMC7917240 DOI: 10.3389/fimmu.2021.613468] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 01/22/2021] [Indexed: 12/15/2022] Open
Abstract
Schistosomiasis remains the fourth most prevalent parasitic disease affecting over 200 million people worldwide. Control efforts have focussed on the disruption of the life cycle targeting the parasite, vector and human host. Parasite burdens are highly skewed, and the majority of eggs are shed into the environment by a minority of the infected population. Most morbidity results from hepatic fibrosis leading to portal hypertension and is not well-correlated with worm burden. Genetics as well as environmental factors may play a role in these skewed distributions and understanding the genetic risk factors for intensity of infection and morbidity may help improve control measures. In this review, we focus on how genetic factors may influence parasite load, hepatic fibrosis and portal hypertension. We found 28 studies on the genetics of human infection and 20 studies on the genetics of pathology in humans. S. mansoni and S. haematobium infection intensity have been showed to be controlled by a major quantitative trait locus SM1, on chromosome 5q31-q33 containing several genes involved in the Th2 immune response, and three other loci of smaller effect on chromosomes 1, 6, and 7. The most common pathology associated with schistosomiasis is hepatic and portal vein fibroses and the SM2 quantitative trait locus on chromosome six has been linked to intensity of fibrosis. Although there has been an emphasis on Th2 cytokines in candidate gene studies, we found that four of the five QTL regions contain Th17 pathway genes that have been included in schistosomiasis studies: IL17B and IL12B in SM1, IL17A and IL17F in 6p21-q2, IL6R in 1p21-q23 and IL22RA2 in SM2. The Th17 pathway is known to be involved in response to schistosome infection and hepatic fibrosis but variants in this pathway have not been tested for any effect on the regulation of these phenotypes. These should be priorities for future studies.
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Affiliation(s)
- Estelle M. Mewamba
- Molecular Parasitology and Entomology Unit, Faculty of Science, University of Dschang, Dschang, Cameroon
| | - Oscar A. Nyangiri
- College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
| | - Harry A. Noyes
- Centre for Genomic Research, School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Moses Egesa
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Enock Matovu
- College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
| | - Gustave Simo
- Molecular Parasitology and Entomology Unit, Faculty of Science, University of Dschang, Dschang, Cameroon
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13
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BARRETO AVMS. LETTER TO EDITOR ABOUT “NEW INDEX FOR THE DIAGNOSIS OF LIVER FIBROSIS IN SCHISTOSOMIASIS MANSONI”. ARQUIVOS DE GASTROENTEROLOGIA 2019; 56:108-109. [DOI: 10.1590/s0004-2803.201900000-09] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 02/27/2019] [Indexed: 12/12/2022]
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Silva FLD, Del-Rei RP, Fraga DBM, Leony LM, Souza AMGCD, Santos FLN. Alterations in the lipid profiles and circulating liver enzymes in individuals infected by Schistosoma mansoni. Rev Soc Bras Med Trop 2019; 51:795-801. [PMID: 30517533 DOI: 10.1590/0037-8682-0113-2018] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 10/02/2018] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION Portal hypertension and periportal fibrosis commonly occur in severe Schistosoma mansoni infection. Changes in lipid profile and elevated levels of circulating liver enzymes have also been described in infected individuals. The present study sought to assess the alterations in laboratory parameters associated with liver disorder in individuals infected by S. mansoni who visited a private routine laboratory service. Levels of circulating liver enzymes (gamma-glutamyl transferase [γ-GT], aspartate transaminase [AST], alanine transaminase [ALT], and alkaline phosphatase [ALP]) and a lipid panel (total cholesterol [COL], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very low-density lipoprotein [VLDL], and triglycerides [TRI]) were evaluated in both infected and non-infected individuals and relative risk was used to measure associations. METHODS Data were collected for analysis from a total of 1,078 cases identified in 379,600 individuals who submitted samples to the Datalab Laboratory (Salvador, Bahia) between 2004 and 2008. RESULTS S. mansoni infection led to increased circulating levels of γ-GT in both women and men, AST (women), and ALP (men). S. mansoni infection was a protective factor against increased levels of TRI, CHO, and VLDL for individuals aged 19 years or older. The results of our analysis indicate that alterations in lipid metabolism and circulating liver enzymes in asymptomatic S. mansoni-infected individuals might be attributed to eggs lodged in the hepatic sinusoids. CONCLUSIONS Parasitological testing for S. mansoni should be indicated in endemic areas when this pattern of alterations is detected.
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Affiliation(s)
- Fabiana Letícia da Silva
- Laboratório de Análise de Sistemas de Informações em Saúde, Instituto Aggeu Magalhães, Recife, PE, Brasil
| | | | | | - Leonardo Maia Leony
- Laboratório Avançado de Saúde Pública, Instituto Gonçalo Moniz, Salvador, BA, Brasil
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