Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review

Machicado, Claudia; Machicado, Jorge D.; Maco, Vicente; Terashima, Angélica; Marcos, Luis A.

doi:10.1371/journal.pntd.0004962

Cited by 71 publications

(63 citation statements)

References 43 publications

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“…Diagnosis is currently performed through the use of high-sensitive serological and parasitological tools. Although most patients are asymptomatic, patients with acute infection normally present fever and abdominal pain, while patients with chronic infection present biliary colic, cholecystitis and cholangitis [4]. Conversely, there is a limited number of studies to evaluate the natural history of patients affected with fascioliasis to assert chronic inflammation, liver fibrosis stages and carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Fasciola Hepatica Extract Induces Cell Death of Mammalian Cells

Ferreira

Fernandes

Botelho

2018

AIA

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Background Fascioliasis is a neglected tropical disease that affects poor people from poor and developing countries. In the world, it has been estimated that at least 2.6 million people are affected with this disease. The International agency for Research on Cancer, states that O. viverrini and C. sinensis, also liver flukes, are considered as definitive causes of cholangiocarcinoma. However, fascioliasis caused by F. hepatica has not been associated with cancer to date. There are not any known causative associations between this parasite and liver cancer (cholangiocarcinoma). Methods Chine Hamster Ovary (CHO) cells were treated with F. hepatica extracts and cell proliferation was assessed by using the indirect method for estimating cell number based on the mitochondrial activity with MTS cell proliferation reagent. We observed unexpected death of these cells when treated with F. hepatica extracts. Results We now hypothesize that this parasite could be used as a medically-important trematode pathogen in cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Fasciola Hepatica Extract Induces Cell Death of Mammalian Cells

Ferreira

Fernandes

Botelho

2018

AIA

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“…Like other helminths, F. hepatica infection and its excretory/secretory products (ESP) inhibit the development of M1 which facilitates the switch to the M2 phenotype, and modulates the host immune response by inducing potent polarized M2 (Th2) and by downregulating the production of M1 (Th1) macrophages [6,7]. Fascioliasis, which is caused by F. hepatica or F. gigantica afflicts at least 2.6 million people around the world [8,9], causes hepatic pathologies such as liver fibrosis, cirrhosis, and even cancer [10]. Moreover, fascioliasis outbreaks caused by F. gigantica in Yunnan, China further suggested that this pathogen might be zoonotic [11].…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product-Induced M2 to M1 Macrophage Polarization

Luo

Zhang

Sheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are well known regulators of gene expression that play essential roles in macrophage activation and polarization. However, the role of lncRNA in Fasciola gigantica excretory/secretory products (ESP)-induced M2 polarization into M1 macrophages is unclear. Herein, we performed lncRNA profiling of lncRNAs and mRNAs during the ESP-induced macrophage polarization process. Methods: F. gigantica ESP was used to induce peritoneal cavity M2 macrophages in BALB/c mice (5-6 weeks old) in vivo, and these cells were subsequently isolated and stimulated with IFN-γ + LPS to induce M1 cells in vitro. LncRNA and mRNA profiling was performed via microarray at the end of both polarization stages. Results: In total, 2,844 lncRNAs (1,579 upregulated and 1,265 downregulated) and 1,782 mRNAs (789 upregulated and 993 downregulated) were differentially expressed in M2 macrophages compared to M1 macrophages, and six lncRNAs were identified during polarization. We selected 34 differentially expressed lncRNAs and mRNAs to validate the results of microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, particularly peptidase activity and carbohydrate metabolism. Furthermore, coding and non-coding gene (CNC) and mRNA-related ceRNA network analyses were conducted to predict lncRNA expression trends and the potential target genes of these lncRNAs and mRNAs. Moreover, we determined that four lncRNAs and four mRNAs might participate in F. gigantica ESP-induced M2 polarization into M1 macrophages. Conclusions: This study illustrates the basic profiling of lncRNAs and mRNAs during F. gigantica ESP-induced M2 polarization into M1 macrophages and deepens our understanding of the mechanism underlying this process.

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“…m/z 571) and as well as DNA-adducts (m/z 599) [4]. This was expected since these parasites all reside within the bile ducts and fascioliasis can induce DNA damage [10,17]. To reiterate, however, these were fewer of these compounds in F. hepatica compared to Opisthorchis spp.…”

Section: Resultsmentioning

confidence: 99%

“…results in comparable pathology in their definitive hosts including fibrosis, hyperplasia and biliary stasis [3,10,21–23]. However, an association between fascioliasis and cancer remains controversial and not definitely established [10]. Thus, we decided to investigate extracts of adult worms of F. hepatica and compare with data previously obtained for Opisthorchis spp.…”

Section: Discussionmentioning

confidence: 99%

“…Other factors such as DNA repair and cell proliferation key roles players in determining the overall carcinogenic risk [32]. An association between fascioliasis and cancer has only been suggested from in vitro studies and, thus far, there have not been satisfactory reports of human cases of bile duct cancer due to chronic infection with F. hepatica [10,14,33–35]. Therefore, there is a lack of cogent evidence that relate fascioliasis with cancer [10].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

Gouveia

Pakharukova

Sripa

et al. 2019

Preprint

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50 Chronic infections with the flatworm parasites Opisthorchis viverrini, Clonorchis sinensis and 51 Schistosoma haematobium are classified as group 1 biological carcinogens, i.e. definitive causes 52 of cancer. In addition, we reported findings that support the inclusion of Opisthorchis felineus in 53 this list of biological carcinogens. By contrast, infections with close phylogenetic relatives 54 including Fasciola hepatica have not been associated with carcinogenesis. Earlier reports revealed 55 of oxysterol metabolites of Opisthorchis liver fluke origin conjugated with DNA bases, suggesting 56 that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of 57 the infection with these food-borne pathogens. Here we employed liquid chromatography-mass 58 spectrometry (LC-MS/MS) to investigate, compare and contrast spectrograms of soluble extracts 59 from F. hepatica adult worms from bile ducts of cattle with those from O. viverrini and O. felineus 60 from experimentally-infected hamsters. F. hepatica displayed a complex spectrophotometric 61 profile. F. hepatica and Opisthorchis spp. shared several common compounds including oxysterol-62 like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of these Opisthorchis 63 species included far fewer compounds than F. hepatica. These findings support the postulate that 64 oxysterol-like metabolites of parasite origin can initiate carcinogenesis and they point to a 65 molecular basis for the inconsistencies among major groups of liver flukes concerning infection-66 induced malignancy. 67 (202 words) 68 69 70 71 72 73 4 74 Author Summary 75 Several species of trematodes are parasites of the human hepatobiliary tract. Infection with 76 two of these flukes, Clonorchis sinsensis and Opisthorchis viverrini, fresh water fish-borne 77 parasites that occur in East Asia is classified as group 1 carcinogens by the International Agency 78 for Research on Cancer (IARC), i.e. definitive causes of cancer in humans. By contrast, infection 79 with a different liver fluke, Fasciola hepatica, does not lead to malignant transformation of the 80 biliary tract. Given the close phylogeny of all three parasites, this difference in carcinogenicity is 81 intriguing and, if explained, likely of value in novel therapeutic approaches. The importance of the 82 current findings is informative because they present a mass spectrometric analysis and catalog of 83 the similarities and differences between fluke of the genus Opisthorchis and F. hepatica, 84 potentially identifying carcinogenic metabolites of liver fluke origin. These metabolites can be 85 expected to provide deeper understanding of helminth infection induced malignancy. 86 (149 words) 87 88 89 90 91 92 Keywords 93 Fasciola hepatica, Opisthorchis viverrini; Opisthorchis felineus; oxysterols; DNA adducts 94 95 5 96 97 More than 20% of cancer in the developing world are caused by infections [1]. The World 98 Health Organization's International Agency for Research on Cancer (IARC) recognizes ...

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Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review

Cited by 71 publications

References 43 publications

Fasciola Hepatica Extract Induces Cell Death of Mammalian Cells

Fasciola Hepatica Extract Induces Cell Death of Mammalian Cells

Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product-Induced M2 to M1 Macrophage Polarization

Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

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