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Sample records for liver fluke clonorchis

  1. [A Study On The Fine Structure Of Clonorchis Sinensis, A Liver Fluke: 1. The Body Wall And The Nervous System

    PubMed

    Jeong, Kye Heon; Rim, Han Jong; Kim, Chang Whan

    1978-12-01

    A morphological study on the ultrastructures of body wall and the nervous system of Clonorchis sinensis was conducted. For this study, liver flukes were collected from the liver of rabbit six months after the infection with metacercariae obtained from the fresh water fish, Pseudorasbora parva. The collected materials were washed with 0.85% saline solution and then immediately moved to cold 2.5% glutaraldehyde buffered with 0.1 M Millonig's phosphate buffer (pH 7.4). The materials were dissected into appropriate pieces in the fixative about 30 minutes after beginning of the fixation. Two hours later the materials were rinsed several times with the buffer and were fixed with cold, buffered 1% osmium tetroxide(OsO(4)) for 2 hours. The fully fixed tissue blocks were dehydrated in a series of graded concentrations of acetone and were embedded in Epon 812 mixture. Thin sections obtained from Sorvall MT-2 ultramicrotome were stained with uranyl acetate and Reynold's lead citrate. Observations of the sections were carried out with Hitachi HS-7S electron microscope. The following structures are newly identifed in a series of observations. 1. The mid-abdominal integument of the fluke is more thicker(~6 micrometer) than the dorsal side(about 3 micrometer). 2. Although it is so far known that only surface and epithelia of the suckers, pharynx, and the oesophagus are composed of integumental, anuclear layer, it is newly found that epithelium of the excretory pore also consists of integumental, anuclear layer. 3. There are lot of microvilli in the dorsal outer surface of the oral sucker. 4. A kind of ducts accumulated with unknown secretory granules are present within the parenchyrna around both of the oral suckers and the pharynx. 5. The nerve endings are distributed to the integument of the body where sensory hairs are projected outward. 6. The sensory hairs are rarely distributed throughout the whole integument, but a little more in the surroundings of both suckers. 7. The sensory hairs are attached to the base of the sheath by a circular septate desmosome. 8. No rootlet structure is observed but the upper part of the basal body is attached to the peripheral desmosome by transverse fibres. 9. The mitochondria and the vesicles are present within the hair cavity. 10. The nerve fibres are also found to be myelinated at least in main axons. PMID:12902777

  2. Liver Flukes: the Malady Neglected

    PubMed Central

    2011-01-01

    Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause human infection are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Adult flukes settle in the small intrahepatic bile ducts and then they live there for 20-30 years. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. The vast majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. The complications are stone formation, recurrent pyogenic cholangitis and cholangiocarcinoma. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the impact of this food-borne malady on public health and the severe possible clinical consequences, liver fluke infection should not be forgotten or neglected. PMID:21603286

  3. The liver fluke Opisthorchis felineus: biology, epidemiology and carcinogenic potential.

    PubMed

    Pakharukova, Mariya Y; Mordvinov, Viatcheslav A

    2016-01-01

    The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically important liver fluke species belonging to the family Opisthorchiidae and the major agent causing opisthorchiasis over a vast territory, covering Russia, Kazakhstan and several European countries. The similarity between the diseases caused by O. felineus and other liver flukes, O. viverrini and Clonorchis sinensis, in clinical manifestations and course suggests that the scenarios of their development and, possibly, complications have much in common. The International Agency for Research on Cancer classified O. viverrini and C. sinensis as group 1 agents and the major factors inducing cholangiocarcinoma in endemic regions. However, a carcinogenic potential of O. felineus is poorly studied. This review characterizes O. felineus, briefs the epidemiological situation in Western Siberia, the world's largest opisthorchiasis focus, and assesses the carcinogenic potential of this liver fluke. The review is based on a comprehensive analysis of the published medical data on opisthorchiasis and its complications in Western Siberia. Results of performed analysis reflect the actual epidemiological situation in opisthorchiasis focus and suggest an association of this disease with bile duct cancer. PMID:26740360

  4. Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis

    PubMed Central

    Yang, Qing-Li; Shen, Ji-Qing; Xue, Yan; Cheng, Xiao-Bing; Jiang, Zhi-Hua; Yang, Yi-Chao; Chen, Ying-Dan; Zhou, Xiao-Nong

    2015-01-01

    The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins. PMID:26797449

  5. Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis.

    PubMed

    Yang, Qing-Li; Shen, Ji-Qing; Xue, Yan; Cheng, Xiao-Bing; Jiang, Zhi-Hua; Yang, Yi-Chao; Chen, Ying-Dan; Zhou, Xiao-Nong

    2015-12-01

    The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins. PMID:26797449

  6. Is Opisthorchis viverrini an avian liver fluke?

    PubMed

    Nawa, Y; Doanh, P N; Thaenkham, U

    2015-03-01

    Recently, in the Journal of Helminthology (May 2013), Dao et al. reported that Opisthorchis viverrini-like flukes were found in the bile duct of domestic ducks in Vietnam. They stated that this is the first record of Opisthorchis sp. in birds in Vietnam. However, three Opisthorchis species--O. cheelis, O. longissimus and O. parageminus--in birds in Vietnam were described by Le in 2000. Amongst these, O. parageminus was first reported, by Oshmarin in 1970, as a new Opisthorchis species found in domestic ducks (Anas platyrhynchos) in Vietnam. Morphologially O. viverrini-like flukes described by Dao et al. are much more similar to O. parageminus than to O. viverrini. The phylogenetic trees of internal transcribed spacer 2 (ITS2) and cytochrome oxidase 1 (CO1) gene sequences also showed that the O. viverrini-like liver flukes from domestic ducks were closer to O. lobatus than to O. viverrini. Therefore, O. viverrini-like liver flukes reported by Dao et al. (2013) are most likely to be O. parageminus. PMID:24160690

  7. The tumorigenic liver fluke Opisthorchis viverrini--multiple pathways to cancer.

    PubMed

    Sripa, Banchob; Brindley, Paul J; Mulvenna, Jason; Laha, Thewarach; Smout, Michael J; Mairiang, Eimorn; Bethony, Jeffrey M; Loukas, Alex

    2012-10-01

    Liver fluke infection caused by Opisthorchis viverrini is a major public health problem in Thailand and adjacent countries. In addition to infection-associated morbidity, infection with O. viverrini and the related Clonorchis sinensis are unarguable risk factors for cholangiocarcinoma (CAA, bile-duct cancer). Here we review the pathogenesis of opisthorchiasis and the association between O. viverrini infection and bile-duct cancer, focusing on the molecular parallels between wound healing, chronic inflammation, and cancer development. We review a schema for human disease progression from fluke infection, chronic opisthorchiasis, advanced periductal fibrosis, and cholangiocarcinogenesis, and present a rationale for biomarker discovery to facilitate early intervention. We conclude by addressing post-genomic advances with a view to developing new control strategies to combat this infectious cancer. PMID:22947297

  8. Development of Experimental Vaccines Against Liver Flukes.

    PubMed

    Yap, Huan Yong; Smooker, Peter M

    2016-01-01

    A multitude of experimental vaccines have been developed against liver flukes in the past. However, there has yet to be the development of a commercial livestock vaccine. Reasons for this may be multiple, and include the lack of identification of the best antigen(s), or the immune response induced by those antigens not being appropriate in either magnitude or polarity (and therefore not protective). Cathepsin proteases are the major component of the excretory/secretory (ES) material of liver flukes in all stages of their life cycle in the definitive host and are the primary antigens of interest for the vaccine development in many studies. Hence, this chapter presents the methodologies of using cathepsin proteases as targeted antigens in recombinant protein and DNA vaccine development to engender protective immune responses against fasciolosis.First, the experimental vaccines developed in the past and the criteria of an effective vaccine for fasciolosis are briefly reviewed. Then flowcharts for recombinant protein vaccine and DNA vaccine development are presented, followed by the detailed materials and methodologies. PMID:27076295

  9. Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers

    PubMed Central

    Correia da Costa, José M.; Vale, Nuno; Gouveia, Maria J.; Botelho, Mónica C.; Sripa, Banchob; Santos, Lúcio L.; Santos, Júlio H.; Rinaldi, Gabriel; Brindley, Paul J.

    2014-01-01

    Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture. PMID:25566326

  10. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus.

    PubMed

    Pakharukova, Mariya Y; Vavilin, Valentin A; Sripa, Banchob; Laha, Thewarach; Brindley, Paul J; Mordvinov, Viatcheslav A

    2015-12-01

    The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium) are considered by the International Agency for Research on Cancer (IARC) as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i) to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii) to assess CYP ability to metabolize xenobiotics, and (iii) to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR) in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target. PMID:26625139

  11. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus

    PubMed Central

    Pakharukova, Mariya Y.; Vavilin, Valentin A.; Sripa, Banchob; Laha, Thewarach; Brindley, Paul J.; Mordvinov, Viatcheslav A.

    2015-01-01

    The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium) are considered by the International Agency for Research on Cancer (IARC) as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i) to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii) to assess CYP ability to metabolize xenobiotics, and (iii) to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR) in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target. PMID:26625139

  12. Apoptosis of cholangiocytes modulated by thioredoxin of carcinogenic liver fluke.

    PubMed

    Matchimakul, Pitchaya; Rinaldi, Gabriel; Suttiprapa, Sutas; Mann, Victoria H; Popratiloff, Anastas; Laha, Thewarach; Pimenta, Rafael N; Cochran, Christina J; Kaewkes, Sasithorn; Sripa, Banchob; Brindley, Paul J

    2015-08-01

    Chronic infection with the food-borne liver fluke, Opisthorchis viverrini, frequently induces cancer of the bile ducts, cholangiocarcinoma. Opisthorchiasis is endemic in Thailand, Lao PDR, Cambodia and Vietnam, where eating undercooked freshwater fish carrying the juvenile stage of this pathogen leads to human infection. Because inhibition of apoptosis facilitates carcinogenesis, this study investigated modulation by thioredoxin from O. viverrini of apoptosis of bile duct epithelial cells, cholangiocytes. Cells of a cholangiocyte line were incubated with the parasite enzyme after which they were exposed hydrogen peroxide. Oxidative stress-induced apoptosis was monitored using flow cytometry, growth in real time and imaging of living cells using laser confocal microscopy. Immunolocalization revealed liver fluke thioredoxin within cholangiocytes. Cells exposed to thioredoxin downregulated apoptotic genes in the mitogen activated protein kinases pathway and upregulated anti-apoptosis-related genes including apoptosis signaling kinase 1, caspase 9, caspase 8, caspase 3, survivin and others. Western blots of immunoprecipitates of cell lysates revealed binding of thioredoxin to apoptosis signaling kinase 1. Together the findings indicated that thioredoxin from O. viverrini inhibited oxidative stress-induced apoptosis of bile duct epithelial cells, which supports a role for this liver fluke oxidoreductase in opisthorchiasis-induced cholangiocarcinogenesis. PMID:26007234

  13. Oxidative stress-mediated mouse liver lesions caused by Clonorchis sinensis infection.

    PubMed

    Maeng, Sejung; Lee, Hye Won; Bashir, Qudsia; Kim, Tae Im; Hong, Sung-Jong; Lee, Tae Jin; Sohn, Woon-Mok; Na, Byoung-Kuk; Kim, Tong-Soo; Pak, Jhang Ho

    2016-03-01

    Clonorchis sinensis is a high-risk pathogenic helminth that strongly provokes inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma in chronically infected individuals. Chronic inflammation is associated with an increased risk of various cancers due to the disruption of redox homeostasis. Accordingly, the present study was conducted to examine the time course relationship between histopathological changes and the appearance of oxidative stress markers, including lipid peroxidation, enzymes involved in lipid peroxidation, and mutagenic DNA adducts in the livers of mice infected with C. sinensis, as well as proinflammatory cytokines in infected mouse sera. Histopathological phenotypes such as bile duct epithelial hyperplasia, periductal fibrosis, edema and inflammatory infiltration increased in infected livers in a time-dependent manner. Intense immunoreactivity of lipid peroxidation products (4-hydroxy-2-nonenal; malondialdehyde), cyclooxygenase-2, 5-lipoxygenase and 8-oxo-7,8-dihydro-2'-deoxyguanosine were concomitantly observed in these injured regions. We also found elevated expressions of cyclooxygenase-2 and 5-lipoxygenase in C. sinensis excretory-secretory product-treated cholangiocarcinoma cells. Moreover, the levels of proinflammatory cytokines such as TNF-α, ILβ-1 and IL-6 were differentially upregulated in infected sera. With regard to oxidative stress-mediated carcinogenesis, our findings suggest that C. sinensis infestation may disrupt host redox homeostasis, creating a damaging environment that favors the development of advanced hepatobiliary diseases such as clonorchiasis-associated cholangiocarcinoma. PMID:26718397

  14. Retrotransposon OV-RTE-1 from the carcinogenic liver fluke Opisthorchis viverrini: potential target for DNA-based diagnosis.

    PubMed

    Thi Phung, Luyen; Loukas, Alex; Brindley, Paul J; Sripa, Banchob; Laha, Thewarach

    2014-01-01

    Infections by the fish-borne liver flukes Opisthorchis viverrini and Clonorchis sinensis can lead to bile duct cancer. These neglected tropical disease pathogens occur in East Asia, with O. viverrini primarily in Thailand and Laos and C. sinensis in Cambodia, Vietnam, and China. Genomic information about these pathogens holds the potential to improve disease treatment and control. Transcriptome analysis indicates that mobile genetic elements are active in O. viverrini, including a novel non-Long Terminal Repeat (LTR) retrotransposon. A consensus sequence of this element, termed OV-RTE-1, was assembled from expressed sequence tags and PCR amplified genomic DNA. OV-RTE-1 was 3330 bp in length, encoded 1101 amino acid residues and exhibited hallmark structures and sequences of non-LTR retrotransposons including a single open reading frame encoding apurinic-apyrimidinic endonuclease (EN) and reverse transcriptase (RT). Phylogenetic analyses confirmed that OV-RTE-1 was member of the RTE clade of non-LTR retrotransposons. OV-RTE-1 is the first non-LTR retrotransposon characterized from the trematode family Opisthorchiidae. Sequences of OV-RTE-1 were targeted to develop a diagnostic tool for detection of infection by O. viverrini. PCR specific primers for detection of O. viverrini DNA showed 100% specificity and sensitivity for detection of as little as 5 fg of O. viverrini DNA whereas the PCR based approach showed 62% sensitivity and 100% specificity with clinical stool samples. The OV-RTE-1 specific PCR could be developed as a molecular diagnostic for Opisthorchis infection targeting parasite eggs in stool samples, especially in regions of mixed infection of O. viverrini and/or C. sinensis and minute intestinal flukes. PMID:24394447

  15. Retrotransposon OV-RTE-1 from the carcinogenic liver fluke Opisthorchis viverrini; potential target for DNA-based diagnosis

    PubMed Central

    Phung, Luyen Thi; Loukas, Alex; Brindley, Paul J.; Sripa, Banchob; Laha, Thewarach

    2014-01-01

    Infections by the fish-borne liver flukes Opisthorchis viverrini and Clonorchis sinensis can lead to bile duct cancer. These neglected tropical disease pathogens occur in East Asia, with O. viverrini primarily in Thailand and Laos and C. sinensis in Cambodia, Vietnam, and China. Genomic information about these pathogens holds the potential to improve disease treatment and control. Transcriptome analysis indicates that mobile genetic elements are active in O. viverrini, including a novel non-Long Terminal Repeat (LTR) retrotransposon. A consensus sequence of this element, termed OV-RTE-1, was assembled from expressed sequence tags and PCR amplified genomic DNA. OV-RTE-1 was 3,330 bp in length, encoded 1,101 amino acid residues and exhibited hallmark structures and sequences of non-LTR retrotransposons including a single open reading frame encoding apurinic-apyrimidinic endonuclease (EN) and reverse transcriptase (RT). Phylogenetic analyses confirmed that OV-RTE-1 was member of the RTE clade of non-LTR retrotransposons. OV-RTE-1 is the first non-LTR retrotransposon characterized from the trematode family Opisthorchiidae. Sequences of OV-RTE-1 were targeted to develop a diagnostic tool for detection of infection by O. viverrini. PCR specific primers for detection of O. viverrini DNA showed 100% specificity and sensitivity for detection of as little as five femtograms of O. viverrini DNA whereas the PCR based approach showed 62% sensitivity and 100% specificity with clinical stool samples. The OV-RTE-1 specific PCR could be developed as a molecular diagnostic for Opisthorchis infection targeting parasite eggs in stool samples, especially in regions of mixed infection of O. viverrini and/or C. sinensis and minute intestinal flukes. PMID:24394447

  16. Potential targeted therapy for liver fluke associated cholangiocarcinoma.

    PubMed

    Vaeteewoottacharn, Kulthida; Seubwai, Wunchana; Bhudhisawasdi, Vajarabhongsa; Okada, Seiji; Wongkham, Sopit

    2014-06-01

    Biliary tree cancer or cholangiocarcinoma (CCA) is an unusual subtype of liver cancer with exceptionally poor prognosis. Lack of specific symptoms and availability of early diagnostic markers account for late diagnosis of CCA. Surgical treatment is a gold standard choice but few patients are candidates and local recurrence after surgery is high. Benefit of systemic chemotherapy is limited; hence, better treatment options are required. The differences in etiology, anatomical positions and pathology make it difficult to generalize all CCA subtypes for a single treatment regimen. Herein, we review the uniqueness of molecular profiling identified by multiple approaches, for example, serial analysis of gene expression, exome sequencing, transcriptomics/proteomics profiles, protein kinase profile, etc., that provide the opportunity for treatment of liver fluke-associated CCA. Anti-inflammatory, immunomodulator/immunosuppressor, epidermal growth factor receptor or platelet-derived growth factor receptor inhibitors, multi-targeted tyrosine kinase inhibitor, IL6 antagonist, nuclear factor-?B inhibitor, histone modulator, proteasome inhibitor as well as specific inhibitors suggested from various study approaches, such as MetAP2 inhibitor, 1,25(OH)2 D3 and cyclosporine A are suggested in this review for the treatments of this specific CCA subtype. This might provide an alternative treatment option for CCA patients; however, clinical trials in this specific CCA group are required. PMID:24408866

  17. Molecular identification and phylogenetic analysis of nuclear rDNA sequences among three opisthorchid liver fluke species (Opisthorchiidae: Trematoda).

    PubMed

    Kang, Seokha; Sultana, Tahera; Loktev, Valery B; Wongratanacheewin, Surasakdi; Sohn, Woon-Mok; Eom, Keeseon S; Park, Joong-Ki

    2008-06-01

    In this study, we describe the development of a fast and accurate molecular identification system for human-associated liver fluke species (Opisthorchis viverrini, Opisthorchis felineus, and Clonorchis sinensis) using the PCR-RFLP analysis of the 18S-ITS1-5.8S nuclear ribosomal DNA region. Based on sequence variation in the target rDNA region, we selected three species-specific restriction enzymes within the ITS1 regions, generating different restriction profiles among the species: MunI for O. viverrini, NheI for O. felineus, and XhoI for C. sinensis, respectively. Each restriction enzyme generated different-sized fragments specific to the species examined, but no intraspecific polymorphism or cross-reaction between the species was detected in their restriction pattern. These results indicate that PCR-linked restriction analysis of the ITS1 region allows for the rapid and reliable molecular identification among these opisthorchid taxa. In addition, phylogenetic analysis of rDNA sequences using different methods (MP, ML, NJ, and Bayesian inference) displayed O. viverrini and O. felineus as a sister group, but this relationship was not strongly supported. The failure of recovering a robust phylogeny may be due to the relatively small number of synapomorphic characters shared among the species, yielding weak phylogenetic signal. Alternatively, rapid speciation within a very short period time could be another explanation for the relatively poorly resolved relationships among these species. Our data are insufficient for discriminating between sudden cladogenesis and other potential causes of poor resolution. Further information from independent loci might help resolve this phylogeny. PMID:18276183

  18. Composition and metabolism of phospholipids of Fasciola hepatics, the common liver fluke.

    PubMed

    Oldenborg, V; Van Vugt, F; Van Golde, L M

    1975-07-22

    1. The phospholipid composition of Fasciola hepatica, the common liver fluke, was compared to that of the liver of the host animals (rats and cattle). Considerable differences were found:monoacyl-sn-glycero-3-phosphorylcholine, hardly detectable in the liver, was found in significant amounts in the parasite. On the other hand, sphingomyelin, a normal constituent in the liver, appears to be absent in the liver fluke. Fasciola hepatica isolated from rat and cow liver had a strikingly similar phospholipid composition. 2. Qualitative and quantitative differences were also found between the fatty acyl constituents of the phospholipids of the parasite and the liver. The major difference was the presence of eicosaenoic and eicosadienoic acids in the parasite, whereas these acids were not detected in the liver. 3. In vitro incubations of Fasciola hepatica in the presence of (32P)phosphate and (2-3H)glycerol resulted in the labelling of all phospholipids of the parasite, except that the 3H label did not incorporate into ethanolamine plasmalogen. This is in agreement with the concept that in animals, glycerol is introduced into plasmalogens via dihydroxyacetonephosphate. 4. Homogenates of liver flukes were found to catalyze the synthesis of phosphatidylcholine from 1,2-diacyl-sn-glycerols and CDPcholine. 5. These results strongly suggest that Fasciola hepatica is capable of synthesizing at least part of its fatty acids and phospholipids. PMID:1148265

  19. Association between Liver Fluke Infection and Hepatobiliary Pathological Changes: A Systematic Review and Meta-Analysis

    PubMed Central

    Xia, Jing; Jiang, Shi-chen; Peng, Hong-Juan

    2015-01-01

    Objective To provide information about the role of liver fluke infection as a risk factor for hepatobiliary pathological changes and promote awareness among the people living in endemic areas, a systematic review and meta-analysis based on published studies was conducted to examine the association between liver fluke infection and hepatobiliary pathological changes. Methods Relevant original literature was searched in multiple literature databases, including PubMed, Cochrane, Clinical Evidence, Trip Database, Clinical Trials, Current Controlled Trials, Web of Science, the China National Knowledge Infrastructure (CNKI) database, and the Wanfang academic journal full-text database. Studies were selected based on strict screening with inclusion and exclusion criteria. Tests of heterogeneity, sensitivity and publication bias were performed with the Review Manager software, version 5.3, and meta-regression analyses were performed with the Stata software, version 11.0 (Stata Corporation, College Station, TX, USA). Pooled risk ratios (RRs) and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated and used to evaluate the risk of hepatobiliary pathological changes resulting from liver fluke infection. Linear trend analyses were conducted to determine the dose-response relationship using IBM SPSS Statistics 20.0. Result A total of 36 studies were included in the meta-analysis. Significant associations were found between liver fluke infection and cholangitis or cholecystitis (RR: 7.80, P<0.001; OR: 15.98, P<0.001), cholelithiasis (RR: 2.42, P = 0.03; OR: 4.96, P = 0.03), hepatocellular carcinoma (OR: 4.69, P<0.001) and cholangiocarcinoma (RR: 10.43, P<0.001; OR: 4.37, P<0.001). In addition, heavier infection was significantly associated with higher incidence of hepatobiliary pathological changes (P<0.05). However, cirrhosis was not significantly associated with liver fluke infection (RR: 3.50, P = 0.06; OR: 5.79, P = 0.08). The statistical heterogeneity was significant, no significant difference was observed in the sensitivity analysis, and no publication bias was found. Conclusion The meta-analysis found that liver fluke infection was significantly associated with cholangitis, cholecystitis, cholelithiasis, hepatocellular carcinoma and cholangiocarcinoma and that more severe infection was associated with higher incidence. However, the association between liver fluke infection and cirrhosis was not significant. PMID:26186510

  20. Experimental infection of liver flukes, Fasciola hepatica and Fascioloides magna, in Bison (Bison bison).

    PubMed

    Foreyt, William J; Drew, M L

    2010-01-01

    This experimental study was conducted to evaluate the susceptibility of American bison (Bison bison) to liver flukes, Fascioloides magna and Fasciola hepatica. Six bison were each experimentally inoculated with 600 metacercariae of Fascioloides magna, and three were later treated with triclabendazole suspension at 40 mg/kg of body weight. Four additional bison were each experimentally inoculated with 600 metacercariae of Fasciola hepatica. Five control bison were placebo controls. Two controls and all inoculated bison were euthanized 10 mo (Fascioloides magna) and 7 mo (Fasciola hepatica) after inoculation. None of the control bison or the bison inoculated with Fascioloides magna had flukes or lesions characteristic of fluke infection at necropsy. All four bison inoculated with Fasciola hepatica had characteristic liver fluke lesions at necropsy, and three of four bison contained four, 103, and 111 adult flukes, respectively. Fluke eggs were detected in feces of all Fasciola hepatica-inoculated bison during the experiment, but not from the Fascioloides magna-infected bison or control bison. Clinical signs of infection were not observed during the experiment, but hemoglobin and packed cell volumes were lower in the Fasciola hepatica bison when compared to controls, and eosinophil levels were increased. Triclabendazole at 40 mg/kg of body weight appeared to be safe in bison because no toxic reactions were observed. Results from this study indicated bison are susceptible to infection with Fasciola hepatica and are efficient definitive hosts. Because no Fascioloides magna were recovered, bison may have a decreased susceptibility or innate resistance to Fascioloides magna infection, which may account for a lack of reported infections in this host. PMID:20090045

  1. Liver fluke-infested graft used for living-donor liver transplantation: case report and review of the literature.

    PubMed

    Capobianco, I; Frank, M; Königsrainer, A; Sipos, B; Menzel, M; Sturm, E; Nadalin, S

    2015-12-01

    Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also known as liver flukes. Clonorchiasis is endemic in a wide geographical area extending from Eastern Europe to Southeast Asia. Infested hosts may remain asymptomatic for decades and consequently their liver can become available as a graft. To date, 20 liver transplantations with liver fluke-infested grafts have been reported in the literature. All of them occurred in Asian countries. We, here, report the first case to our knowledge in the Western world of living-donor liver transplantation (LDLT) with an Opisthorchis felineus-infested graft, and present a review of the literature. A 6-month-old girl with decompensated secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested with O. felineus. After prompt diagnosis and adequate therapy, both donor and recipient had an uneventful postoperative course and long-term follow-up. Liver grafts infested with liver flukes do not pose a contraindication to liver donation from deceased or living donors, provided that a correct diagnosis and treatment are performed in a timely fashion. PMID:26437122

  2. A model to assess the efficacy of vaccines for control of liver fluke infection

    PubMed Central

    Turner, Joanne; Howell, Alison; McCann, Cathy; Caminade, Cyril; Bowers, Roger G.; Williams, Diana; Baylis, Matthew

    2016-01-01

    Fasciola hepatica, common liver fluke, infects cattle and sheep causing disease and production losses costing approximately $3billion annually. Current control relies on drugs designed to kill the parasite. However, resistance is evident worldwide and widespread in some areas. Work towards a vaccine has identified several antigens of F. hepatica that show partial efficacy in terms of reducing worm burden and egg output. A critical question is what level of efficacy is required for such a vaccine to be useful? We have created the first mathematical model to assess the effectiveness of liver fluke vaccines under simulated field conditions. The model describes development of fluke within a group of animals and includes heterogeneity in host susceptibility, seasonal exposure to metacercariae and seasonal changes in temperature affecting metacercarial survival. Our analysis suggests that the potential vaccine candidates could reduce total fluke burden and egg output by up to 43% and 99%, respectively, on average under field conditions. It also suggests that for a vaccine to be effective, it must protect at least 90% of animals for the whole season. In conclusion, novel, partial, vaccines could contribute substantially towards fasciolosis control, reducing usage of anthelmintics and thus delaying the spread of anthelmintic resistance. PMID:27009747

  3. A model to assess the efficacy of vaccines for control of liver fluke infection.

    PubMed

    Turner, Joanne; Howell, Alison; McCann, Cathy; Caminade, Cyril; Bowers, Roger G; Williams, Diana; Baylis, Matthew

    2016-01-01

    Fasciola hepatica, common liver fluke, infects cattle and sheep causing disease and production losses costing approximately $3billion annually. Current control relies on drugs designed to kill the parasite. However, resistance is evident worldwide and widespread in some areas. Work towards a vaccine has identified several antigens of F. hepatica that show partial efficacy in terms of reducing worm burden and egg output. A critical question is what level of efficacy is required for such a vaccine to be useful? We have created the first mathematical model to assess the effectiveness of liver fluke vaccines under simulated field conditions. The model describes development of fluke within a group of animals and includes heterogeneity in host susceptibility, seasonal exposure to metacercariae and seasonal changes in temperature affecting metacercarial survival. Our analysis suggests that the potential vaccine candidates could reduce total fluke burden and egg output by up to 43% and 99%, respectively, on average under field conditions. It also suggests that for a vaccine to be effective, it must protect at least 90% of animals for the whole season. In conclusion, novel, partial, vaccines could contribute substantially towards fasciolosis control, reducing usage of anthelmintics and thus delaying the spread of anthelmintic resistance. PMID:27009747

  4. Effects of the injectable contraceptive depot medroxyprogesterone acetate in Thai women with liver fluke infestation: results after six months

    PubMed Central

    Grossman, Richard A.; Assawasena, Vinich; Chalpati, Sopon; Taewtong, Dilok

    1977-01-01

    The effect of the three-monthly injectable contraceptive depot medroxyprogesterone acetate (DMPA) on liver and lipid function was assessed in Thai women with liver fluke (Opisthorchis viverrini) infestation, DMPA administration being started in the immediate postpartum period. Immediate postpartum IUD and sterilization acceptors with fluke infestation were recruited as a comparison (control) group for the fluke-positiv DMPA acceptors. Comparable groups of fluke-negative acceptors were recruited in an area of Thailand free of liver fluke transmission. Results are presented for the first 6 follow-up months for 170 DMPA and 177 control fluke-positive subjects and for 153 DMPA and 150 control fluke-negative subjects. Small and similar increases occurred in each of the four groups for alanine amino transferase, isocitrate dehydrogenase, and total bilirubin levels while aspartate amino transferase levels changed less in the DMPA groups than in their respective control groups. None of the subjects in either DMPA group had clearly abnormal results in these tests at 6 months. Alkaline phosphatase, cholesterol, and triglycerides levels were markedly lower in each group at 6 months than in the puerperal specimens. There was a greater decrease in triglycerides levels in both DMPA groups than in their respective control groups. However, the decrease in the alkaline phosphatase and cholesterol levels was greater only in the fluke-positive DMPA group than in the fluke-positive control group. None of these biochemical results were related to differences in age, parity, or lactation status between the groups. The results indicate that DMPA did not cause any early deleterious effects in the metabolic factors studied in women with liver fluke infestation. PMID:302157

  5. Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome

    PubMed Central

    Plieskatt, Jordan L.; Deenonpoe, Raksawan; Mulvenna, Jason P.; Krause, Lutz; Sripa, Banchob; Bethony, Jeffrey M.; Brindley, Paul J.

    2013-01-01

    Opisthorchis viverrini is a fish-borne trematode endemic in East Asia. Following ingestion, the flukes locate to the biliary treȩ where chronic infection frequently leads to cholangiocarcinoma (CCA). The mechanisms by which O. viverrini infection culminates in CCA remain unknown. An unexplored aspect is its influence on the host microbiome. In the hamster, infection with this pathogen reliably leads to CCA. Genomic DNAs of microbiota from colorectal contents and bile of hamsters and from whole O. viverrini were examined in this model of fluke-induced CCA. Microbial communities were characterized by high-throughput sequencing of variable regions 7–9 of prokaryotic 16S ribosomal DNA. Of ∼1 million sequences, 536,009 with useable reads were assignable to 29,776 operational taxonomy units (OTUs) and, in turn, to 20 phyla and 273 genera of Bacteria or Archaea. Microbial community analyses revealed that fluke infection perturbed the gastrointestinal tract microbiome, increasing Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae, while decreasing Porphyromonadaceae, Erysipelotrichaceae, and Eubacteriaceae (P≤0.05). More than 60 OTUs were detected in the biliary system, which confirmed bacteriobilia and a noteworthy community of microbes associated with the parasites. The fluke-associated microorganisms included potential pathogens from the Enterobacteriaceae and Listeriaceae and others, including Cyanobacteria and Deinococci, usually found in external environments. Given that opisthorchiasis is distinguished from other helminth infections by a robust inflammatory phenotype with conspicuously elevated IL-6, and that inflammation of the biliary system leads to periductal fibrosis, which is a precursor of CCA, the flukes and their microbiota may together drive this distinctive immune response.—Plieskatt, J. L., Raksawan, D., Mulvenna, J. P., Krause, L., Sripa, B., Bethony, J. M., Brindley, P. J. Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome. PMID:23925654

  6. Current status of Clonorchis sinensis and clonorchiasis in China.

    PubMed

    Lai, De-Hua; Hong, Xiao-Kun; Su, Bi-Xiu; Liang, Chi; Hide, Geoff; Zhang, Xiaoli; Yu, Xinbing; Lun, Zhao-Rong

    2016-01-01

    The oriental liver fluke, Clonorchis sinensis, a pathogen causing clonorchiasis, is of major socio-economic importance in East Asia, including China, Korea and Vietnam. This parasite is now recognized as a biocarcinogen strongly linked to cholangiocarcinoma in humans. Here, we describe the status of clonorchiasis in China, where it has been estimated that more than 15 million patients are affected. This paper also summarizes the major advances in the field of clonorchiasis research during last decade, including diagnosis techniques, pathogenesis and genome/transcriptome/proteome studies in the last years. We strongly hope that our work can stimulate the governments of the countries or regions where clonorchiasis is endemic to pay more attention to this disease and establish related guidelines to prevent and control it. PMID:26740359

  7. Clonorchis sinensis and Opisthorchis spp. in Vietnam: current status and prospects.

    PubMed

    Doanh, Pham N; Nawa, Yukifumi

    2016-01-01

    Clonorchis sinensis and Opisthorchis viverrini are clinically important small liver flukes because of their known association with development of cholangiocarcinoma. In Vietnam, high prevalence of C. sinensis infection in humans was previously reported in northern provinces, and O. viverrini infection has been detected in several central provinces. However, diagnosis of C. sinensis and O. viverrini infections in the past was merely based on faecal egg examination. This method alone can lead to misidentification at the species level because of morphological similarity between the eggs of these liver flukes and minute intestinal trematodes of the family Heterophyidae. In fact, recent surveys in Vietnam revealed that infection with several minute intestinal flukes, such as Haplorchis pumilio and H. taichui, are much more common than infection with C. sinensis or O. viverrini, and they often co-infect humans. Thus, previously reported prevalence of small liver fluke infection in Vietnam was likely over-estimated due to mis identification of parasites in copro-parasitological examinations. In addition, there is some confusion about identification of cercariae, metacercariae and also adults of C. sinensis and O. viverrini in intermediate and definitive hosts. The aim of this review is, therefore, to draw realistic pictures of the past and present scientific reports on the epidemiology and biology of C. sinensis and Opisthorchis spp. infection in Vietnam. PMID:26740358

  8. Proteomic profile of Bithynia siamensis goniomphalos snails upon infection with the carcinogenic liver fluke Opisthorchis viverrini

    PubMed Central

    Prasopdee, Sattrachai; Tesana, Smarn; Cantacessi, Cinzia; Laha, Thewarach; Mulvenna, Jason; Grams, Rudi; Loukas, Alex; Sotillo, Javier

    2014-01-01

    The snail Bithynia siamensis goniomphalos acts as the first intermediate host for the human liver fluke Opisthorchis viverrini, the major cause of cholangiocarcinoma (CCA) in Northeast Thailand. The undisputed link between CCA and O. viverrini infection has precipitated efforts to understand the molecular basis of host-parasite interactions with a view to ultimately developing new control strategies to combat this carcinogenic infection. To date most effort has focused on the interactions between the parasite and its human host, and little is known about the molecular relationships between the liver fluke and its snail intermediate host. In the present study we analyse the protein expression changes in different tissues of B. siamensis goniomphalos induced by infection with larval O. viverrini using iTRAQ labelling technology. We show that O. viverrini infection downregulates the expression of oxidoreductases and catalytic enzymes, while stress-related and motor proteins are upregulated. The present work could serve as a basis for future studies on the proteins implicated in the susceptibility/resistance of B. siamensis goniomphalos to O. viverrini, as well as studies on other pulmonate snail intermediate hosts of various parasitic flukes that infect humans. PMID:25284051

  9. Suppression of aquaporin, a mediator of water channel control in the carcinogenic liver fluke, Opisthorchis viverrini

    PubMed Central

    2014-01-01

    Background Opisthorchiasis and Opisthorchis viverrini-associated bile duct cancer represent major public health threats in Thailand and Laos. The tegument of this food borne fluke plays pivotal roles in parasite metabolism, homeostasis and osmoregulation. Excretory/secretory products also pass from the fluke to the biliary environment, products that likely underlie pathogenesis of liver fluke infection. Aquaporins (AQPs), belong to the major intrinsic protein superfamily of integral plasma membrane channel proteins that selectively transport water across cell membranes. AQPs play key roles as water and ion transport channels through the tegument of helminth parasites. Methods Here, two forms of AQP mRNAs from the adult developmental stage of O. viverrini, termed O. viverrini aquaporin-1 and -2 (Ov-aqp-1 and -2) were investigated. Roles of Ov-aqp-1 and -2 in the movement of water across the tegument of this carcinogenic liver fluke were investigated using RNA interference. Results Ov-AQP-1 and Ov-AQP-2 contain unique characteristic asparagine-proline-alanine (NPA) motifs of AQP transmembrane proteins. Phylogenetic analysis indicated that Ov-AQPs belong to an expanding group of aquaglyceroporin-like water channel proteins characterized from helminth and protozoan parasites, which is pivotal to the specialized requirements of water and solute control during parasitism. Elevated transcription of Ov-aqp-1 was evident in the egg, cercaria, metacercaria and adult stages of O. viverrini, whereas Ov-aqp-2 transcripts were detected at higher level in egg, metacercaria, cercaria and adult stage, respectively. RNA interference using electroporated dsRNA suppressed transcript levels of Ov-aqp-1 and Ov-aqp-2 in adult worms by 58-99% over periods of up to 16 days in vitro. Suppression of Ov-aqp-1 and Ov-aqp-2 in vitro disabled water transport in adult flukes. Conclusion The apparently pivotal roles of Ov-AQP in solute homeostasis at the fluke surface suggest that deeper investigation will be informative for the pathophysiology of O. viverrini, and may uncover intervention targets, particularly in view of the singularly notable predilection of this pathogen for residence within ducts of the biliary tree. PMID:24885060

  10. RNAi Dynamics in Juvenile Fasciola spp. Liver Flukes Reveals the Persistence of Gene Silencing In Vitro

    PubMed Central

    McVeigh, Paul; McCammick, Erin M.; McCusker, Paul; Morphew, Russell M.; Mousley, Angela; Abidi, Abbas; Saifullah, Khalid M.; Muthusamy, Raman; Gopalakrishnan, Ravikumar; Spithill, Terry W.; Dalton, John P.; Brophy, Peter M.; Marks, Nikki J.; Maule, Aaron G.

    2014-01-01

    Background Fasciola spp. liver fluke cause pernicious disease in humans and animals. Whilst current control is unsustainable due to anthelmintic resistance, gene silencing (RNA interference, RNAi) has the potential to contribute to functional validation of new therapeutic targets. The susceptibility of juvenile Fasciola hepatica to double stranded (ds)RNA-induced RNAi has been reported. To exploit this we probe RNAi dynamics, penetrance and persistence with the aim of building a robust platform for reverse genetics in liver fluke. We describe development of standardised RNAi protocols for a commercially-available liver fluke strain (the US Pacific North West Wild Strain), validated via robust transcriptional silencing of seven virulence genes, with in-depth experimental optimisation of three: cathepsin L (FheCatL) and B (FheCatB) cysteine proteases, and a σ-class glutathione transferase (FheσGST). Methodology/Principal Findings Robust transcriptional silencing of targets in both F. hepatica and Fasciola gigantica juveniles is achievable following exposure to long (200–320 nt) dsRNAs or 27 nt short interfering (si)RNAs. Although juveniles are highly RNAi-susceptible, they display slower transcript and protein knockdown dynamics than those reported previously. Knockdown was detectable following as little as 4h exposure to trigger (target-dependent) and in all cases silencing persisted for ≥25 days following long dsRNA exposure. Combinatorial silencing of three targets by mixing multiple long dsRNAs was similarly efficient. Despite profound transcriptional suppression, we found a significant time-lag before the occurrence of protein suppression; FheσGST and FheCatL protein suppression were only detectable after 9 and 21 days, respectively. Conclusions/Significance In spite of marked variation in knockdown dynamics, we find that a transient exposure to long dsRNA or siRNA triggers robust RNAi penetrance and persistence in liver fluke NEJs supporting the development of multiple-throughput phenotypic screens for control target validation. RNAi persistence in fluke encourages in vivo studies on gene function using worms exposed to RNAi-triggers prior to infection. PMID:25254508

  11. Comparative proteomic analysis of triclabendazole response in the liver fluke Fasciola hepatica.

    PubMed

    Chemale, Gustavo; Perally, Samirah; LaCourse, E James; Prescott, Mark C; Jones, Laura M; Ward, Deborah; Meaney, Myles; Hoey, Elizabeth; Brennan, Gerard P; Fairweather, Ian; Trudgett, Alan; Brophy, Peter M

    2010-10-01

    Control of Fasciola hepatica infections of livestock in the absence of vaccines depends largely on the chemical triclabendazole (TCBZ) because it is effective against immature and adult parasites. Overdependence on a single drug and improper application is considered a significant factor in increasing global reports of fluke resistant to TCBZ. The mode(s) of action and biological target(s) of TCBZ are not confirmed, delaying detection and the monitoring of early TCBZ resistance. In this study, to further understand liver fluke response to TCBZ, the soluble proteomes of TCBZ-resistant and TCBZ-susceptible isolates of F. hepatica were compared with and without in vitro exposure to the metabolically active form of the parent drug triclabendazole sulphoxide (TCBZ-SO), via two-dimensional gel electrophoresis (2-DE). Gel image analysis revealed proteins displaying altered synthesis patterns and responses both between isolates and under TCBZ-SO exposure. These proteins were identified by mass spectrometry supported by a F. hepatica expressed sequence tag (EST) data set. The TCBZ responding proteins were grouped into three categories; structural proteins, energy metabolism proteins, and "stress" response proteins. This single proteomic investigation supported the reductionist experiments from many laboratories that collectively suggest TCBZ has a range of effects on liver fluke metabolism. Proteomics highlighted differences in the innate proteome profile of different fluke isolates that may influence future therapy and diagnostics design. Two of the TCBZ responding proteins, a glutathione transferase and a fatty acid binding protein, were cloned, produced as recombinants, and both found to bind TCBZ-SO at physiologically relevant concentrations, which may indicate a role in TCBZ metabolism and resistance. PMID:20726552

  12. Opisthorchis viverrini (liver fluke) as the lot of baleful parasite of tropical region-A replete synopsis

    PubMed Central

    Gundamaraju, Rohit; Vemuri, Ravi Chandra

    2014-01-01

    Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts which is highly prominent in the tropical regions. Infection occurs through ingestion of fluke-infested fresh-water raw fish. Opisthorchis viverrini is the biggest causative organism for this disease. Adult flukes get into the body of humans and settle in the small intrahepatic bile ducts, and then they live there for few decades. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts, and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. Major complications of the disease also include pancreatitis, bile duct obstruction etc. The majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the appulse of this food-borne malady on accessible bloom and the astringent accessible analytic consequences, alarmist accident infection should not be abandoned or neglected. This review acts as a complete picture in elucidating the information regarding the parasite and disease condition thereby supporting the researchers worldwide.

  13. GIS-based spatial statistical analysis of risk areas for liver flukes in Surin Province of Thailand.

    PubMed

    Rujirakul, Ratana; Ueng-arporn, Naporn; Kaewpitoon, Soraya; Loyd, Ryan J; Kaewthani, Sarochinee; Kaewpitoon, Natthawut

    2015-01-01

    It is urgently necessary to be aware of the distribution and risk areas of liver fluke, Opisthorchis viverrini, for proper allocation of prevention and control measures. This study aimed to investigate the human behavior, and environmental factors influencing the distribution in Surin Province of Thailand, and to build a model using stepwise multiple regression analysis with a geographic information system (GIS) on environment and climate data. The relationship between the human behavior, attitudes (<50%; X111), environmental factors like population density (148-169 pop/km2; X73), and land use as wetland (X64), were correlated with the liver fluke disease distribution at 0.000, 0.034, and 0.006 levels, respectively. Multiple regression analysis, by equations OV=-0.599+0.005(population density (148-169 pop/km2); X73)+0.040 (human attitude (<50%); X111)+0.022 (land used (wetland; X64), was used to predict the distribution of liver fluke. OV is the patients of liver fluke infection, R Square=0.878, and, Adjust R Square=0.849. By GIS analysis, we found Si Narong, Sangkha, Phanom Dong Rak, Mueang Surin, Non Narai, Samrong Thap, Chumphon Buri, and Rattanaburi to have the highest distributions in Surin province. In conclusion, the combination of GIS and statistical analysis can help simulate the spatial distribution and risk areas of liver fluke, and thus may be an important tool for future planning of prevention and control measures. PMID:25824758

  14. Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy?

    PubMed

    Fairweather, Ian

    2011-08-01

    The liver fluke remains an economically significant parasite of livestock and is emerging as an important zoonotic infection of humans. The incidence of the disease has increased in the last few years, as a possible consequence of changes to the World's climate. Future predictions suggest that this trend is likely to continue. Allied to the changing pattern of disease, reports of resistance to triclabendazole (TCBZ) have appeared in the literature, although they do not all represent genuine cases of resistance. Nevertheless, any reports of resistance are a concern, because triclabendazole is the only drug that has high activity against the migratory and damaging juvenile stages of infection. How to deal with the twin problems (of increasing incidence and drug resistance) is the overall theme of the session on "Trematodes: Fasciola hepatica epidemiology and control" and of this review to introduce the session. Greater knowledge of fluke epidemiology and population genetics will highlight those regions where surveillance is most required and indicate how quickly resistant populations of fluke may arise. Models of disease risk are becoming increasingly sophisticated and precise, with more refined data analysis programmes and Geographic Information Systems (GIS) data. Recent improvements have been made in our understanding of the action of triclabendazole and the ways in which flukes have become resistant to it. While microtubules are the most likely target for drug action, tubulin mutations do not seem to be involved in the resistance mechanism. Rather, upregulation of drug uptake and metabolism processes appear to be more important and the data relating to them will be discussed. The information may help in the design of new treatment strategies or pinpoint potential molecular markers for monitoring fluke populations. Advances in the identification of novel targets for drugs and vaccines will be made by the various "-omics" technologies that are now being applied to Fasciola. A major area of concern in the current control of fasciolosis is the lack of reliable tests for the diagnosis of drug (TCBZ) resistance. This has led to inaccurate reports of resistance, which is hindering successful disease management, as farmers may be encouraged to switch to less effective drugs. Progress with the development of a number of new diagnostic tests will be reviewed. PMID:21703766

  15. Molecular expression and enzymatic characterization of thioredoxin from the carcinogenic human liver fluke Opisthorchis viverrini

    PubMed Central

    Suttiprapa, Sutas; Matchimakul, Pitchaya; Loukas, Alex; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Brindley, Paul J.; Sripa, Banchob

    2013-01-01

    The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for years. Defense against oxidative damage can be mediated through glutathione and/or thioredoxin utilising systems. Here, we report the molecular expression and biochemical characterization of a thioredoxin (Trx) from O. viverrini. O. viverrini Trx cDNA encoded a polypeptide of 105 amino acid residues, of molecular mass 11.63 kDa. The predicted protein has similarity to previously characterized thioredoxins with 26-51% identity. Recombinant O. viverrini Trx (Ov-Trx-1) was expressed as soluble protein in E. coli. The recombinant protein showed insulin reduction activity and supported the enzymatic function of O. viverrini thioredoxin peroxidase. Expression of Ov-Trx-1at mRNA and protein levels were observed in all obtainable developmental stages of the liver fluke. Ov-Trx-1 was also detected in excretory-secretory products released by adult O. viverrini. Immunohistochemsitry, Ov-Trx-1 was expressed in nearly all parasite tissue excepted ovary and mature sperms. Interestingly, Ov-Trx-1 was observed in the infected biliary epithelium but not normal bile ducts. These results suggest that Ov-Trx-1 is essential for the parasite throughout the life cycle. In the host-parasite interaction aspect, Ov-Trx-1 may support thioredoxin peroxidase in protecting the parasite against damage induced by reactive oxygen species from inflammation. PMID:21740981

  16. Metabolism of drugs and other xenobiotics in giant liver fluke (Fascioloides magna).

    PubMed

    Prchal, Lukáš; Vokřál, Ivan; Kašný, Martin; Rejšková, Lenka; Zajíčková, Markéta; Lamka, Jiří; Skálová, Lenka; Lecová, Lenka; Szotáková, Barbora

    2016-02-01

    1. Giant liver fluke Fascioloides magna is a dangerous parasite, which infects herbivores. It was imported to Europe from North America and started to spread. Benzimidazoles like albendazole, mebendazole, triclabendazole and salicylanilides closantel and rafoxanide are the most used anthelmintics to control fascioloidosis. However their effect might be altered via drug-metabolizing enzymes of this parasite. 2. The aim of our study was to determine the activities of drug-metabolizing enzymes in F. magna and the metabolism of above mentioned anthelmintics. 3. Activities of several oxidative, reductive and conjugative enzymes towards various model xenobiotic substrates were found in F. magna subcellular fractions. 4. Subcellular fractions from F. magna oxidized albendazole to its sulphoxide metabolite and reduced mebendazole to hydroxyl-mebendazole. Under ex vivo conditions, only very-low concentrations of these compounds were detected using high-performance liquid chromatography/mass spectrometry. 5. The results indicate that the giant liver fluke possesses the active xenobiotic-metabolizing system. The overexpression of this system may play an important role in parasite resistance against these anthelmintics. PMID:26153440

  17. DIAGNOSIS AND THERAPY OF LIVER FLUKE (FASCIOLOIDES MAGNA) INFECTION IN FALLOW DEER (DAMA DAMA) IN SERBIA.

    PubMed

    Trailović, Saša M; Marinković, Darko; Kulišić, Zoran

    2016-04-28

    Giant liver fluke ( Fascioloides magna ) infection is an important health problem of cervids in southeastern Europe. We measured the prevalence and intensity of infection with F. magna in a fenced area near the Danube River in the South Bačka District of Serbia. Parasitologic, pathomorphologic, and histopathologic examinations were conducted from November 2007 to February 2008, beginning with a population of 127 adult fallow deer ( Dama dama ). After a positive diagnosis, therapy with triclabendazole-medicated corn was applied. Deer were treated at four baiting stations, using medicated feed providing triclabendazole at an estimated dose of 10-14 mg/kg of body weight per deer. Treatment lasted for 7 d in early February 2008 and an additional 7 d 2 wk later. For the complete success of pharmacotherapy it was necessary to prevent any contact of deer with the snail intermediate host ( Galba truncatula ). Intervention in the habitat, removing grass and low vegetation, and draining ponds reduces the possibility of contact. Six months after the treatment, livers of hunted deer were reddish, with fibrous tracks; pigmentation and cysts in the parenchyma were surrounded by a fibrous capsule and their fecal samples contained no eggs of F. magna . Over the following years, livers of hunted deer were negative, and the last control cull in March 2015 confirmed complete absence of infection. We reconfirmed the presence of giant liver flukes in fallow deer in Serbia, apparently the result of natural spread across the Danube from Hungary and Croatia. We also report that the treatment of deer with triclabendazole-medicated corn is an effective method for administration of therapeutic doses of drug in semicaptive deer. Interventions in the environment are necessary to prevent recontact of deer with habitats used by the snail intermediate host, and enable the success of the therapy. PMID:26967130

  18. In vitro screening of Cymbopogon jwarancusa and Conyza canadensis against liver flukes.

    PubMed

    Shafiq, Andeela; Kanwal, Rabia; Ullah Qureshi, Rahamat; Riaz Chaudhry, Farhana

    2015-09-01

    Aim of present study was to screen medicinal plants for flukicidal activity in vitro to develop alternative sources of treatment for trematodes infection. For this purpose, crude methanolic extracts (CME) of Cymbopogn jwarancusa and Conyza canadensis were prepared and live adult flukes viz; Fasciola gigantica, and Paramphistomum cervi isolated from liver and bile ducts of slaughtered buffalo were subjected to different drug concentrations as well as positive and negative control. Motility inhibition and paralysis leading to the death of parasites was considered as flukicidal activity of plants extracts. The results revealed that CME of C. jwarancusa and C. canadensis showed significant (P<0.05) flukicidal activity compared to positive control. Also there was a significant effect of different concentrations (P<0.05) and exposure of time on the flukes (P<0.05). Furthermore, ED50 for C. jwarancusa and C. canadensis against F. gigantica were 13.1 and 41.4 mg/ml, respectively. In the case of P. cervi, it was 10.8 and 29.0 mg/ml. It can be concluded that both tested plants showed greater flukicidal activity as compared to positive control with Albendazole till the 8(th) hr. These potent plants needs further studies invivo to elucidate their mode of action. PMID:26695200

  19. Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype

    PubMed Central

    Chaiyadet, Sujittra; Sotillo, Javier; Smout, Michael; Cantacessi, Cinzia; Jones, Malcolm K.; Johnson, Michael S.; Turnbull, Lynne; Whitchurch, Cynthia B.; Potriquet, Jeremy; Laohaviroj, Marut; Mulvenna, Jason; Brindley, Paul J.; Bethony, Jeffrey M.; Laha, Thewarach; Sripa, Banchob; Loukas, Alex

    2015-01-01

    Background. Throughout Asia, there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes, including chronic inflammation and secretion of parasite proteins into the biliary epithelium, drive infection toward cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown. Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterized the EV proteome and associated changes in cholangiocytes after EV uptake, and we detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and interleukin 6 (IL-6) secretion was measured to assess the impact of EV internalization. Results. EVs were identified in fluke culture medium and bile specimens from infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair, and cancer. Antibodies to an O. viverrini tetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes. Conclusions. This is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this infectious cancer. PMID:25985904

  20. An expanding population of the giant liver fluke (Fascioloides magna) in elk (Cervus canadensis) and other ungulates in Canada.

    PubMed

    Pybus, Margo J; Butterworth, Eric W; Woods, John G

    2015-04-01

    Giant liver fluke (Fascioloides magna) populations readily expand under suitable conditions. Although extirpated from the eastern slopes of the Canadian Rocky Mountains in the early 1960s, the fluke reappeared following natural spread through mountain passes from British Columbia. Herein, we assessed epizootiology of the fluke population two decades later. Between 1984 and 1991, 534 ungulates, including 381 elk (Cervus canadensis), 68 mule deer (Odocoileus hemionus hemionus), 54 white-tailed deer (Odocoileus virginianus), and 31 moose (Alces alces) from adjacent areas of Alberta (AB) and British Columbia (BC), Canada, were examined for giant liver flukes. Prevalence in elk increased from 53% to 79% (1984-91) in Banff National Park (BNP) in AB and 77% to 100% (1985-89) in Kootenay National Park (KNP) in BC. Super-infections (>100 flukes) were more common in later years. Generally, prevalence increased over time and with increasing age of elk. Intensity was lowest in young-of-year (BNP 8±5, KNP 3), but similar in yearlings (BNP 36±11, KNP 23±8) and adults (BNP 33±5, KNP 32±6). Prevalence was similar in male and female elk. Intensity was higher in males (BNP 47±7, KNP 46±12) than in females (BNP 28±6, KNP 22±4), although the maximum number of flukes (545) occurred in a female elk. Prevalence and intensity differed among other species of ungulates but patterns were similar in each park. Prevalence was lower in mule deer (BNP 6%, KNP 4%) than in white-tailed deer (BNP 44%, KNP 28%) and moose (BNP 52%, KNP 63%). Intensity differed among these species but never exceeded 30 flukes. Gravid flukes occurred only in elk and white-tailed deer. Transmission occurred primarily in late summer-fall and in wet habitats. At least seven elk died as a direct result of fluke infection. In this region, elk and white-tailed deer maintain the F. magna population with spillover into moose and, rarely, mule deer. PMID:25647594

  1. Prevalence of liver fluke infections in slaughtered animals in Lorestan, Iran.

    PubMed

    Ezatpour, Behrouz; Hasanvand, Ali; Azami, Mehdi; Anbari, Khatereh; Ahmadpour, Fatemeh

    2015-12-01

    Fasciola spp. and Dicrocoelium dendriticum as liver flukes, contaminate ruminants and other mammalian extensively and cause major diseases of livestock that create considerable economic losses. This retrospective study has been done to evaluate contamination rate of slaughtered animals with fasciolosis and dicrocoeliosis at Lorestan abattoirs. In this survey, prevalence rate of fasciolosis and dicrocoeliosis in slaughtered animals in a 3-year period (2010-2013) has been analyzed. A total of 356,605 livestock including 265,692 sheep and 90,913 goats were slaughtered in the 3-year period and overall 39,613 (11.1 %) livers were condemned. Fascioliasis and dicrocoeliosis were responsible for 6.3 and 4.8 % of total liver condemnations in this period, respectively. Fasciola spp. and D. dendriticum infection in sheep (7.1 and 5.6 %, respectively) were considerably higher than goats (3.9 and 2.6 %, respectively). The annual prevalence rates showed a significant decline in the fasciolosis and dicrocoeliosis infection in goats (p < 0.001). Data showed significant seasonal pattern for distomatosis in sheep and goats (p < 0.001). Liver condemnations due to fasciolosis were prevalent in sheep and goats slaughtered during spring and autumn, respectively, whereas dicrocoeliosis were common in spring season for both sheep and goats. This survey provides baseline data for the future monitoring of these potentially important parasitic infections in the region. PMID:26688642

  2. Liver fluke-induced hepatic oxysterols stimulate DNA damage and apoptosis in cultured human cholangiocytes.

    PubMed

    Jusakul, Apinya; Loilome, Watcharin; Namwat, Nisana; Haigh, W Geoffrey; Kuver, Rahul; Dechakhamphu, Somkid; Sukontawarin, Pradit; Pinlaor, Somchai; Lee, Sum P; Yongvanit, Puangrat

    2012-03-01

    Oxysterols are cholesterol oxidation products that are generated by enzymatic reactions through cytochrome P450 family enzymes or by non-enzymatic reactions involving reactive oxygen and nitrogen species. Oxysterols have been identified in bile in the setting of chronic inflammation, suggesting that biliary epithelial cells are chronically exposed to these compounds in certain clinical settings. We hypothesized that biliary oxysterols resulting from liver fluke infection participate in cholangiocarcinogenesis. Using gas chromatography/mass spectrometry, we identified oxysterols in livers from hamsters infected with Opisthorchis viverrini that develop cholangiocarcinoma. Five oxysterols were found: 7-keto-cholesta-3,5-diene (7KD), 3-keto-cholest-4-ene (3K4), 3-keto-cholest-7-ene (3K7), 3-keto-cholesta-4,6-diene (3KD), and cholestan-3β,5α,6β-triol (Triol). Triol and 3K4 were found at significantly higher levels in the livers of hamsters with O. viverrini-induced cholangiocarcinoma. We therefore investigated the effects of Triol and 3K4 on induction of cholangiocarcinogenesis using an in vitro human cholangiocyte culture model. Triol- and 3K4-treated cells underwent apoptosis. Western blot analysis showed significantly increased levels of Bax and decreased levels of Bcl-2 in these cells. Increased cytochrome c release from mitochondria was found following treatment with Triol and 3K4. Triol and 3K4 also induced formation of the DNA adducts 1,N(6)-etheno-2'-deoxyadenosine, 3,N(4)-etheno-2'-deoxycytidine and 8-oxo-7,8-dihydro-2'-deoxyguanosine in cholangiocytes. The data suggest that Triol and 3K4 cause DNA damage via oxidative stress. Chronic liver fluke infection increases production of the oxysterols Triol and 3K4 in the setting of chronic inflammation in the biliary system. These oxysterols induce apoptosis and DNA damage in cholangiocytes. Insufficient and impaired DNA repair of such mutated cells may enhance clonal expansion and further drive the change in cellular phenotype from normal to malignant. PMID:22044627

  3. Wherefrom and whereabouts of an alien: the American liver fluke Fascioloides magna in Austria: an overview.

    PubMed

    Sattmann, Helmut; Hörweg, Christoph; Gaub, Larissa; Feix, Anna Sophia; Haider, Michaela; Walochnik, Julia; Rabitsch, Wolfgang; Prosl, Heinrich

    2014-04-01

    The giant liver fluke Fascioloides magna, an invasive species originating from North America, was recorded in Austria in the wild for the first time in 2000. Since then, various data concerning the epidemiology in snail intermediate hosts and cervid final hosts have been reported. Galba truncatula acts as snail intermediate host, and red deer, roe deer and fallow deer act as final hosts. G. truncatula is abundant throughout the region, especially along muddy shores of slow-flowing branches of the river system. Prevalence in deer (20-100 %) is much higher than in snails (0.03-0.2 %). Despite medical treatment of parts of the deer population, the parasite has successfully established itself on both sides of the Danube floodplain environments southeast of Vienna. Genetic analysis revealed that the infection of Austrian deer populations apparently originated from foci in the Czech Republic or from populations of Danube tributaries. Areas adjacent southwards, which will soon be joined through wildlife crossings, have not yet evidenced F. magna. Nonetheless, these environments are inhabited by host snails and deer and therefore constitute suitable habitats for F. magna. Invading alien parasites not only threaten native individual hosts but also influence host populations, thus potentially also modifying parasite communities and interactions. The host range of F. magna includes a variety of potential hosts, notably other Lymnaeidae as potential intermediate hosts and various ungulates, including sheep and cattle, as final hosts. Because eradication after medical treatment was unsuccessful, and due to the risk of further spread of the parasite into unaffected regions, enhanced control strategies need to be developed. We recommend assessment of introduction pathways and dispersal, continuous monitoring of host abundance and distribution and the prevalence of flukes in intermediate and final hosts, as well as coordinated and concerted actions with neighbouring countries. This strategy could help to reduce potential negative impacts of this and other invasive parasites on host populations in Europe. PMID:24535172

  4. Population-Based Intervention for Liver Fluke Prevention and Control in Meuang Yang District, Nakhon Ratchasima Province, Thailand.

    PubMed

    Kompor, Pontip; Muang Karn, Rattikarn; Norkaew, Jun; Kujapun, Jirawoot; Photipim, Mali; Ponphimai, Sukanya; Chavengkun, Wasugree; Phong Paew, Somkiat; Kaewpitoon, Soraya; Rujirakul, Ratana; Wakhuwathapong, Parichart; Phatisena, Tanida; Eaksanti, Thawatchai; Joosiri, Apinya; Polsripradistdist, Poowadol; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

    2016-01-01

    Opisthorchiasis is still a major health problem in rural communities of Thailand. Infection is associated with cholangiocarcinoma (CCA), which is found frequently in Thailand, particularly in the northeastern. Therefore, this study aimed to evaluate the effectiveness of health intervention in the population at risk for opisthorchiasis and CCA. A quasi-experimental study was conducted in Meuang Yang district, Nakhon Ratchasima province, northeastern Thailand, between June and October 2015. Participants were completed health intervention comprising 4 stations; 1, VDO clip of moving adult worm of liver fluke; 2, poster of life cycle of liver fluke; 3, microscopy with adult and egg liver fluke; and 4, brochure with the knowledge of liver fluke containing infection, signs, symptoms, related disease, diagnosis, treatment, prevention, and control. Pre-and-post-test questionnaires were utilized to collect data from all participants. Students paired t-tests were used to analyze differences between before and after participation in the health intervention. Knowledge (mean difference=-7.48, t=-51.241, 95% CI, -7.77, -7.19, p-value =0.001), attitude (mean difference=-9.07, t=-9.818, 95% CI=-10.9, -7.24, p-value=0.001), and practice (mean difference=-2.04, t=-2.688, 95% CI=-3.55, -0.53, p-value=0.008), changed between before and after time points with statistical significance. Community rules were concluded regarding: (1) cooked cyprinoid fish consumption; (2) stop under cooked cyprinoid fish by household cooker; (3) cooked food consumption; (4) hygienic defecation; (5) corrected knowledge campaign close to each household; (6) organizing a village food safety club; (7) and annual health check including stool examination featuring monitoring by village health volunteers and local public health officers. The results indicates that the present health intervention program was effective and easy to understand, with low cost and taking only a short time. Therefore, this program may useful for further work at community and provincial levels for liver fluke prevention and control. PMID:26925664

  5. Molecular evidence shows that the liver fluke Fasciola gigantica is the predominant Fasciola species in ruminants from Pakistan.

    PubMed

    Chaudhry, U; van Paridon, B; Shabbir, M Z; Shafee, M; Ashraf, K; Yaqub, T; Gilleard, J

    2016-03-01

    Fascioliasis is an important disease affecting livestock, with great costs to producers worldwide. It has also become a serious issue for human populations in some endemic areas as an emerging zoonotic infection. There are two Fasciola species of liver fluke responsible for this disease, which occur worldwide, Fasciola hepatica and Fasciola gigantica. Identifying these two species on the basis of adult or egg morphology requires specialist knowledge due to the similarity of characters, and may misidentify putative intermediate or hybrid forms. In this study we sequenced the internal transcribed spacer 2 (ITS-2) rDNA of liver flukes collected from multiple species of hosts from seven localities in the Punjab and Baluchistan provinces of Pakistan, to determine the distribution of these two species. All 46 flukes processed in this study, collected from seven sites, showed the rDNA ITS-2 genotype corresponding to F. gigantica, contradicting previous reports, based on adult and egg morphology, that both species are present in Pakistan, with F. hepatica being the more common. PMID:25758445

  6. Fasciola hepatica: Histological changes in the somatic and reproductive tissues of liver fluke following closantel treatment of experimentally-infected sheep.

    PubMed

    Scarcella, S; Hanna, R E B; Brennan, G P; Solana, H; Fairweather, I

    2016-01-15

    Lambs infected with the Cullompton isolate of Fasciola hepatica were treated orally or subcutaneously with 10mg/kg of closantel at 16 weeks post-infection. Adult flukes were recovered from the liver of individual animals at 12h, 24h, or 36h post-treatment. The flukes were processed for histological analysis. In general, degenerative changes in the reproductive and somatic tissues were progressive, and were most marked in flukes exposed to closantel in vivo for 36h. However, flukes from a 12h subcutaneously-treated lamb showed marked deterioration of the testis, possibly because a portion of the dose has been delivered intravenously. Fewer intact eggs were seen in the uterus of flukes exposed to closantel for longer times (whether administered subcutaneously or orally to the host). The most conspicuous closantel-induced effect in flukes from treated hosts was progressive damage to the tegumental syncytium. While the flukes from 24h-treated hosts showed relatively minor damage to limited areas of the syncytium, towards the posterior end, the flukes from 36h-treated hosts (and flukes from the lamb that putatively received intravenous dosage) had lost large areas of the surface syncytium from the posterior end and dorsal surface, although the syncytium over the anterior end and the anterior ventral surface was largely spared. In areas where the syncytium had sloughed, the underlying structures such as the vitelline follicles, gut profiles and testis profiles, showed marked degeneration and breakdown. Other changes included cell depletion and early stage apoptosis in the testis, ovary and vitelline follicles. This study establishes a model for histological changes in closantel-sensitive F. hepatica exposed to closantel in vivo. Histopathological studies could be complementary to the efficacy controlled test for for closantel resistance in fluke populations. PMID:26790736

  7. Development of mitochondrial loop-mediated isothermal amplification for detection of the small liver fluke Opisthorchis viverrini (Opisthorchiidae; Trematoda; Platyhelminthes).

    PubMed

    Le, Thanh Hoa; Nguyen, Nga Thi Bich; Truong, Nam Hai; De, Nguyen Van

    2012-04-01

    Mitochondrial DNA sequences offer major advantages over the more usual nuclear targets for loop-mediated isothermal amplification approaches (mito-LAMP) because multiple copies occur in every cell. Four LAMP primers [F3, FIP(F1c+F2), BIP(B1c+B2), and B3] were designed based on the mitochondrial nad1 sequence of Opisthorchis viverrini and used for a highly specific assay (mito-OvLAMP) to distinguish DNA of O. viverrini from that of another opisthorchiid (Clonorchis sinensis) and other trematodes (Haplorchis pumilio, Haplorchis taichui, Fasciola hepatica, and Fasciola gigantica). Conventional PCR was applied using F3/B3 primer pairs to verify the specificity of the primers for O. viverrini DNA templates. All LAMP-positive samples could be detected with the naked eye in sunlight, by gel electrophoresis (stained with ethidium bromide), and by addition of SYBR green I to the product in sunlight or under UV light. Only DNA from O. viverrini yielded amplification products by LAMP (and by PCR verification), and the LAMP limit of detection was as little as 100 fg (10(-4) ng DNA), indicating that this assay is 10 to 100 times more sensitive than PCR. Field testing was done using representative egg and metacercarial samples collected from localities where the fluke is endemic. With the advantages of simplicity, rapidity, sensitivity, and cost effectiveness, mito-OvLAMP is a good tool for molecular detection and epidemiology studies in regions or countries where O. viverrini is endemic, which can lead to more effective control of opisthorchiasis and trematodiasis. PMID:22322346

  8. The role of hepatic myofibroblasts in liver cirrhosis in fallow deer (Dama dama) naturally infected with giant liver fluke (Fascioloides magna)

    PubMed Central

    2013-01-01

    Background This paper describes liver cirrhosis in 35 fallow deer infected with the giant liver fluke, as well as the distribution, origin, and role of myofibroblasts in its development. Results In liver of infected deer, stripes of connective tissue are wound around groups of degenerated and regenerated liver lobuli. In the connective tissue, lymphocytes and macrophages which often contain parasite hematin are also present. The walls of the bile ducts are thickened, the epithelium multiplied with mucous metaplasia, and desquamated cells, parasite eggs and brown pigment are present in their lumen. In the livers with cirrhosis, immunopositivity to ?-SMA and desmin was observed in cells in portal and septal spaces, at the edge between fibrotic septa and the surrounding parenchyma and in perisinusoidal spaces. These cells vary in size, they are round, oval, spindle-shaped or irregular in shape, similar to vascular smooth muscle cells. The derangement of epithelial-mesenchymal interactions detected in chronic cholangiopathies is most probably the pro-fibrogenic mechanism in liver cirrhosis of fallow deer (Dama dama) infected with the giant liver fluke (Fascioloides magna). Conclusion Myofibroblasts, especially hepatic stellate cells (HSCs), play an important role in the synthesis of extracellular matrix components in the development of parasitic fibrosis and cirrhosis in the liver of fallow deer. PMID:23497565

  9. Fine-scale mapping of vector habitats using very high resolution satellite imagery: a liver fluke case-study.

    PubMed

    De Roeck, Els; Van Coillie, Frieke; De Wulf, Robert; Soenen, Karen; Charlier, Johannes; Vercruysse, Jozef; Hantson, Wouter; Ducheyne, Els; Hendrickx, Guy

    2014-01-01

    The visualization of vector occurrence in space and time is an important aspect of studying vector-borne diseases. Detailed maps of possible vector habitats provide valuable information for the prediction of infection risk zones but are currently lacking for most parts of the world. Nonetheless, monitoring vector habitats from the finest scales up to farm level is of key importance to refine currently existing broad-scale infection risk models. Using Fasciola hepatica, a parasite liver fluke, as a case in point, this study illustrates the potential of very high resolution (VHR) optical satellite imagery to efficiently and semi-automatically detect detailed vector habitats. A WorldView2 satellite image capable of <5m resolution was acquired in the spring of 2013 for the area around Bruges, Belgium, a region where dairy farms suffer from liver fluke infections transmitted by freshwater snails. The vector thrives in small water bodies (SWBs), such as ponds, ditches and other humid areas consisting of open water, aquatic vegetation and/or inundated grass. These water bodies can be as small as a few m2 and are most often not present on existing land cover maps because of their small size. We present a classification procedure based on object-based image analysis (OBIA) that proved valuable to detect SWBs at a fine scale in an operational and semi-automated way. The classification results were compared to field and other reference data such as existing broad-scale maps and expert knowledge. Overall, the SWB detection accuracy reached up to 87%. The resulting fine-scale SWB map can be used as input for spatial distribution modelling of the liver fluke snail vector to enable development of improved infection risk mapping and management advice adapted to specific, local farm situations. PMID:25599638

  10. Rapid Detection and Differentiation of Clonorchis sinensis and Opisthorchis viverrini Using Real-Time PCR and High Resolution Melting Analysis

    PubMed Central

    Cai, Xian-Quan; Yu, Hai-Qiong; Li, Rong; Yue, Qiao-Yun; Liu, Guo-Hua; Bai, Jian-Shan; Deng, Yan; Qiu, De-Yi; Zhu, Xing-Quan

    2014-01-01

    Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA extracted from the two flukes yielded specific amplification and their identity was confirmed by sequencing, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1 metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to be differentiated by their HRM profiles. The method can reduce labor of microscopic examination and the contamination of agarose electrophoresis. Moreover, it can differentiate these two flukes which are difficult to be distinguished using other methods. The established method provides an alternative tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini. PMID:25386621

  11. The liver flukes Fasciola gigantica and Fasciola hepatica express the leucocyte cluster of differentiation marker CD77 (globotriaosylceramide) in their tegument.

    PubMed

    Wuhrer, M; Berkefeld, C; Dennis, R D; Idris, M A; Geyer, R

    2001-02-01

    Glycosphingolipids from the parasitic liver flukes Fasciola gigantica and Fasciola hepatica were isolated and their carbohydrate moieties were structurally analysed by methylation analysis, exoglycosidase treatment, on-target exoglycosidase cleavage and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. For both liver fluke species, the ceramide monohexosides Gal1-ceramide and Glc1-ceramide were found in relative amounts of 1.0 to 0.1, respectively. From F. gigantica, the ceramide dihexoside was isolated in sufficient amounts to be structurally determined as lactosylceramide, Gal beta4-Glc1-ceramide, while for both liver fluke species the ceramide trihexoside was shown to be Gal alpha4Gal beta4-Glc1-ceramide, which is designated as either globotriaosylceramide, Pk-blood group antigen or CD77 leucocyte cluster of differentiation antigen. To our knowledge, this is the first report on the expression of globo-series glycosphingolipids in non-mammalian species. Ceramide analysis of ceramide monohexosides yielded as major components octadecanoic and 2-hydroxyoctadecanoic fatty acids together with C18- and C20-phytosphingosines. By the use of an anti-CD77 monoclonal antibody and the Escherichia coli Shiga toxin B1 subunit, globotriaosylceramide could be immunolocalised to the tegument of F. hepatica cryosections. The sharing of CD77 between liver flukes and their mammalian hosts fits in with the concept of molecular mimicry, which is closely parallel to the established imitation of host CD15 (Lewis X) displayed by the blood fluke Schistosoma mansoni. PMID:11308018

  12. Expression and cross-species reactivity of fatty acid-binding protein of Clonorchis sinensis.

    PubMed

    Lee, Ji-Sook; Yong, Tai-Soon

    2004-08-01

    Clonorchis sinensis is a Chinese liver fluke that chronically resides in the biliary tract. The fatty acid-binding protein (FABP) is known to play an important role in the intracellular transport of long-chain fatty acids that are obtained by the fluke from the host. Although FABP has stimulated considerable interest as a vaccine target candidate, the nature of FABP from C. sinensis (CsFABP) remains unclear. In this paper, we describe the cloning and expression of recombinant FABP and immune cross-reaction by Western blot analysis. Sequence analysis revealed that the CsFABP cDNA contained a single open reading frame (ORF) coding for 134 amino acids with an estimated molecular mass of a 15.2 kDa. The DNA sequence of CsFABP cDNA showed significant homology to schistosome cytosolic FABPs, with a 49% amino acid sequence identity and 89% similarity to Schistosoma japonicum. This DNA also showed a high sequence similarity at the amino acid level to S. mansoni (Sm14; 83%) and Fasciola hepatica (80%). The CsFABP cDNA was cloned into expression vector pET28a, expressed in Escherichia coli and the recombinant protein purified by affinity chromatography. The recombinant CsFABP was cross-reacted with sera obtained from patients with fascioliasis and paragonimiasis. These results suggest that CsFABP may be useful as a vaccine for clonorchiasis. PMID:15197581

  13. The effects of farm management practices on liver fluke prevalence and the current internal parasite control measures employed on Irish dairy farms.

    PubMed

    Selemetas, Nikolaos; Phelan, Paul; O'Kiely, Padraig; de Waal, Theo

    2015-01-30

    Fasciolosis caused by Fasciola hepatica is responsible for major production losses in cattle farms. The objectives of this study were to assess the effect of farm management practices on liver fluke prevalence on Irish dairy farms and to document the current control measures against parasitic diseases. In total, 369 dairy farms throughout Ireland were sampled from October to December 2013, each providing a single bulk tank milk (BTM) sample for liver fluke antibody-detection ELISA testing and completing a questionnaire on their farm management. The analysis of samples showed that cows on 78% (n=288) of dairy farms had been exposed to liver fluke. There was a difference (P<0.05) between farms where cows were positive or negative for liver fluke antibodies in (a) the total number of adult dairy cows in herds, (b) the number of adult dairy cows contributing to BTM samples, and (c) the size of the total area of grassland, with positive farms having larger numbers in each case. There was no difference (P>0.05) between positive and negative farms in (a) the grazing of dry cows together with replacement cows, (b) whether or not grazed grassland was mowed for conservation, (c) the type of drinking water provision system, (d) spreading of cattle manure on grassland or (e) for grazing season length (GSL; mean=262.5 days). Also, there were differences (P<0.001) between drainage statuses for GSL with farms on good drainage having longer GSL than moderately drained farms. The GSL for dairy cows on farms with good drainage was 11 days longer than for those with moderate drainage (P<0.001). The percentage of farmers that used an active ingredient during the non-lactating period against liver fluke, gastrointestinal nematodes, lungworm, and rumen fluke was 96%, 85%, 77% and 90%, respectively. Albendazole was the most frequently used active ingredient for treatment against gastrointestinal nematodes (57%), liver fluke (40%) and lungworm (47%), respectively. There was a difference (P<0.05) in the use of triclabendazole and albendazole between positive and negative farms, with triclabendazole use being more common in positive farms. This study highlighted differences in dairy management practices between Irish farms with dairy herds exposed or not exposed to liver fluke and stressed the need of fine-scale mapping of the disease patterns even at farm level to increase the accuracy of risk models. Also, comprehensive advice and professional support services to farmers on appropriate farm management practices are very important for an effective anthelmintic control strategy. PMID:25591405

  14. High Prevalence of Human Liver Infection by Amphimerus spp. Flukes, Ecuador

    PubMed Central

    Calvopiña, Manuel; Cevallos, William; Kumazawa, Hideo; Eisenberg, Joseph

    2011-01-01

    Amphimerus spp. flukes are known to infect mammals, but human infections have not been confirmed. Microscopy of fecal samples from 397 persons from Ecuador revealed Opisthorchiidae eggs in 71 (24%) persons. Light microscopy of adult worms and scanning electron microscopy of eggs were compatible with descriptions of Amphimerus spp. This pathogen was only observed in communities that consumed undercooked fish. PMID:22172165

  15. High prevalence of human liver infection by Amphimerus spp. flukes, Ecuador.

    PubMed

    Calvopiña, Manuel; Cevallos, William; Kumazawa, Hideo; Eisenberg, Joseph

    2011-12-01

    Amphimerus spp. flukes are known to infect mammals, but human infections have not been confirmed. Microscopy of fecal samples from 397 persons from Ecuador revealed Opisthorchiidae eggs in 71 (24%) persons. Light microscopy of adult worms and scanning electron microscopy of eggs were compatible with descriptions of Amphimerus spp. This pathogen was only observed in communities that consumed undercooked fish. PMID:22172165

  16. Low Genetic Diversity in Wide-Spread Eurasian Liver Fluke Opisthorchis felineus Suggests Special Demographic History of This Trematode Species

    PubMed Central

    Brusentsov, Ilja I.; Katokhin, Alexey V.; Brusentsova, Irina V.; Shekhovtsov, Sergei V.; Borovikov, Sergei N.; Goncharenko, Grigoriy G.; Lider, Lyudmila A.; Romashov, Boris V.; Rusinek, Olga T.; Shibitov, Samat K.; Suleymanov, Marat M.; Yevtushenko, Andrey V.; Mordvinov, Viatcheslav A.

    2013-01-01

    Opisthorchis felineus or Siberian liver fluke is a trematode parasite (Opisthorchiidae) that infects the hepato-biliary system of humans and other mammals. Despite its public health significance, this wide-spread Eurasian species is one of the most poorly studied human liver flukes and nothing is known about its population genetic structure and demographic history. In this paper, we attempt to fill this gap for the first time and to explore the genetic diversity in O. felineus populations from Eastern Europe (Ukraine, European part of Russia), Northern Asia (Siberia) and Central Asia (Northern Kazakhstan). Analysis of marker DNA fragments from O. felineus mitochondrial cytochrome c oxidase subunit 1 and 3 (cox1, cox3) and nuclear rDNA internal transcribed spacer 1 (ITS1) sequences revealed that genetic diversity is very low across the large geographic range of this species. Microevolutionary processes in populations of trematodes may well be influenced by their peculiar biology. Nevertheless, we suggest that lack of population genetics structure observed in O. felineus can be primarily explained by the Pleistocene glacial events and subsequent sudden population growth from a very limited group of founders. Rapid range expansion of O. felineus through Asian and European territories after severe bottleneck points to a high dispersal potential of this trematode species. PMID:23634228

  17. Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome.

    PubMed

    Plieskatt, Jordan L; Deenonpoe, Raksawan; Mulvenna, Jason P; Krause, Lutz; Sripa, Banchob; Bethony, Jeffrey M; Brindley, Paul J

    2013-11-01

    Opisthorchis viverrini is a fish-borne trematode endemic in East Asia. Following ingestion, the flukes locate to the biliary tre where chronic infection frequently leads to cholangiocarcinoma (CCA). The mechanisms by which O. viverrini infection culminates in CCA remain unknown. An unexplored aspect is its influence on the host microbiome. In the hamster, infection with this pathogen reliably leads to CCA. Genomic DNAs of microbiota from colorectal contents and bile of hamsters and from whole O. viverrini were examined in this model of fluke-induced CCA. Microbial communities were characterized by high-throughput sequencing of variable regions 7-9 of prokaryotic 16S ribosomal DNA. Of ∼1 million sequences, 536,009 with useable reads were assignable to 29,776 operational taxonomy units (OTUs) and, in turn, to 20 phyla and 273 genera of Bacteria or Archaea. Microbial community analyses revealed that fluke infection perturbed the gastrointestinal tract microbiome, increasing Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae, while decreasing Porphyromonadaceae, Erysipelotrichaceae, and Eubacteriaceae (P≤0.05). More than 60 OTUs were detected in the biliary system, which confirmed bacteriobilia and a noteworthy community of microbes associated with the parasites. The fluke-associated microorganisms included potential pathogens from the Enterobacteriaceae and Listeriaceae and others, including Cyanobacteria and Deinococci, usually found in external environments. Given that opisthorchiasis is distinguished from other helminth infections by a robust inflammatory phenotype with conspicuously elevated IL-6, and that inflammation of the biliary system leads to periductal fibrosis, which is a precursor of CCA, the flukes and their microbiota may together drive this distinctive immune response. PMID:23925654

  18. Seasonal differences in the efficacy of pour-on formulations of triclabendazole and ivermectin or abamectin against late immature liver fluke (Fasciola hepatica) in cattle.

    PubMed

    Sargent, R M; Chambers, M; Elliott, T

    2009-04-01

    Three controlled studies were conducted to determine the efficacy against late immature (6 weeks) Fasciola hepatica of two currently available fasciolicides (Genesis Ultra and Coopers Sovereign) which are applied externally to cattle. Efficacy of the two products was assessed when application was made under winter, spring and summer conditions. Efficacies for winter, spring and summer respectively, based on arithmetic mean total fluke counts, were 78.9%, 91.7% and 99.6% for Coopers Sovereign and 73.4%, 89.7% and 99.6% for Genesis Ultra. Seasonal differences with treatment efficacy were indicated. The studies also confirmed previous observations that liver fluke egg counts overestimate the efficacy of fasciolicides and that total fluke counts is the most reliable method for assessing efficacy of such products. PMID:19167826

  19. Induction of cancer-related microRNA expression profiling using excretory-secretory products of Clonorchis sinensis.

    PubMed

    Pak, Jhang Ho; Kim, In Ki; Kim, Seon Min; Maeng, Sejung; Song, Kyoung Ju; Na, Byoung-Kuk; Kim, Tong-Soo

    2014-12-01

    Clonorchis sinensis is a carcinogenic human liver fluke by which chronic infection is strongly associated with the development of cholangiocarcinoma. Although this cholangiocarcinoma is caused by both physical and chemical irritation from direct contact with adult worms and their excretory-secretory products (ESPs), the precise molecular events of the host-pathogen interactions remain to be elucidated. To better understand the effect of C. sinensis infection on cholangiocarcinogenesis, we profiled the kinetics of changes in cancer-related microRNAs (miRNAs) in human cholangiocarcinoma cells (HuCCT1) treated with C. sinensis ESPs for different periods. Using miRNA microarray chips containing 135 cancer-related miRNAs, we identified 16 miRNAs showing differentially altered expression following ESP exposure. Of these miRNAs, 13 were upregulated and 3 were downregulated in a time-dependent manner compared with untreated controls. Functional clustering of these dysregulated miRNAs revealed involvement in cell proliferation, inflammation, oncogene activation/suppression, migration/invasion/metastasis, and DNA methylation. In particular, decreased expression of let-7i, a tumor suppressor miRNA, was found to be associated with the ESP-induced upregulation of TLR4 mRNA and protein, which contribute to host immune responses against liver fluke infection. Further real-time quantitative PCR analysis using ESP-treated normal cholangiocytes (H69) revealed that the expressions of nine miRNAs (miR-16-2, miR-93, miR-95, miR-153, miR-195, miR-199-3P, let7a, let7i, and miR-124a) were similarly regulated, indicating that the cell proliferation and inhibition of tumor suppression mediated by these miRNAs is common to both cancerous and non-cancerous cells. These findings constitute further our understanding of the multiple cholangiocarcinogenic pathways triggered by liver fluke infection. PMID:25217977

  20. A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells.

    PubMed

    Smout, Michael J; Laha, Thewarach; Mulvenna, Jason; Sripa, Banchob; Suttiprapa, Sutas; Jones, Alun; Brindley, Paul J; Loukas, Alex

    2009-10-01

    The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma. PMID:19816559

  1. Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach☆

    PubMed Central

    Cwiklinski, Krystyna; Allen, Katherine; LaCourse, James; Williams, Diana J.; Paterson, Steve; Hodgkinson, Jane E.

    2015-01-01

    The liver fluke, Fasciola hepatica is an economically important pathogen of sheep and cattle and has been described by the WHO as a re-emerging zoonosis. Control is heavily reliant on the use of drugs, particularly triclabendazole and as a result resistance has now emerged. The population structure of F. hepatica is not well known, yet it can impact on host–parasite interactions and parasite control with drugs, particularly regarding the spread of triclabendazole resistance. We have identified 2448 potential microsatellites from 83 Mb of F. hepatica genome sequence using msatfinder. Thirty-five loci were developed and optimised for microsatellite PCR, resulting in a panel of 15 polymorphic loci, with a range of three to 15 alleles. This panel was validated on genomic DNA from 46 adult F. hepatica; 38 liver flukes sourced from a Northwest abattoir, UK and 8 liver flukes from an established isolate (Shrewsbury; Ridgeway Research). Evidence for null alleles was found at four loci (Fh_1, Fh_8, Fh_13 and Fh_14), which showed markedly higher levels of homozygosity than the remaining 11 loci. Of the 38 liver flukes isolated from cattle livers (n = 10) at the abattoir, 37 genotypes were identified. Using a multiplex approach all 15 loci could be amplified from several life cycle stages that typically yield low amounts of DNA, including metacercariae, the infective life cycle stage present on pasture, highlighting the utility of this multiplex microsatellite panel. This study reports the largest panel of microsatellite markers available to date for population studies of F. hepatica and the first multiplex panel of microsatellite markers that can be used for several life cycle stages. PMID:25796359

  2. Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach.

    PubMed

    Cwiklinski, Krystyna; Allen, Katherine; LaCourse, James; Williams, Diana J; Paterson, Steve; Hodgkinson, Jane E

    2015-06-01

    The liver fluke, Fasciola hepatica is an economically important pathogen of sheep and cattle and has been described by the WHO as a re-emerging zoonosis. Control is heavily reliant on the use of drugs, particularly triclabendazole and as a result resistance has now emerged. The population structure of F. hepatica is not well known, yet it can impact on host-parasite interactions and parasite control with drugs, particularly regarding the spread of triclabendazole resistance. We have identified 2448 potential microsatellites from 83 Mb of F. hepatica genome sequence using msatfinder. Thirty-five loci were developed and optimised for microsatellite PCR, resulting in a panel of 15 polymorphic loci, with a range of three to 15 alleles. This panel was validated on genomic DNA from 46 adult F. hepatica; 38 liver flukes sourced from a Northwest abattoir, UK and 8 liver flukes from an established isolate (Shrewsbury; Ridgeway Research). Evidence for null alleles was found at four loci (Fh_1, Fh_8, Fh_13 and Fh_14), which showed markedly higher levels of homozygosity than the remaining 11 loci. Of the 38 liver flukes isolated from cattle livers (n=10) at the abattoir, 37 genotypes were identified. Using a multiplex approach all 15 loci could be amplified from several life cycle stages that typically yield low amounts of DNA, including metacercariae, the infective life cycle stage present on pasture, highlighting the utility of this multiplex microsatellite panel. This study reports the largest panel of microsatellite markers available to date for population studies of F. hepatica and the first multiplex panel of microsatellite markers that can be used for several life cycle stages. PMID:25796359

  3. Genetic and epigenetic alterations of RIZ1 and the correlation to clinicopathological parameters in liver fluke-related cholangiocarcinoma.

    PubMed

    Khaenam, Prasong; Jearanaikoon, Patcharee; Pairojkul, Chawalit; Bhudhisawasdi, Vajarabhongsa; Limpaiboon, Temduang

    2010-03-01

    The retinoblastoma interacting zinc finger (RIZ1) gene is adjacent to D1S228 where microsatellite instability has been associated with poor patient survival in liver fluke-associated cholangiocarcinoma (CCA). An understanding of the molecular mechanisms underlying the carcinogenesis and pathogenesis of CCA is necessary to improve patient survival. Therefore, we determined the genetic and epigenetic alterations of RIZ1 in 81 CCA samples and 69 matched non-tumor tissues. Methylation was found in 31 of 81 (38%) tumor samples and in 5 of 69 (7%) matched non-tumor tissues. Frameshift mutations (2 of 81) and loss of heterozygosity (LOH) (14 of 81) were not common. Statistical analysis found no significant correlation between RIZ1 alterations and clinicopathological features, but RIZPro704 LOH was associated with patient survival in the multivariate analysis. RIZ1 hypermethylation may be one of the crucial molecular events contributing to cholangiocarcinogenesis, and RIZPro704 LOH may adversely impact patient survival. The biological function of RIZ1 in CCA should be further investigated in order to verify its potential role in regulating this cancer. PMID:22993552

  4. Landscape influence on spatial patterns of meningeal worm and liver fluke infection in white-tailed deer.

    PubMed

    Vanderwaal, Kimberly L; Windels, Steve K; Olson, Bryce T; Vannatta, J Trevor; Moen, Ron

    2015-04-01

    Parasites that primarily infect white-tailed deer (Odocoileus virginianus), such as liver flukes (Fascioloides magna) and meningeal worm (Parelaphostrongylus tenuis), can cause morbidity and mortality when incidentally infecting moose (Alces alces). Ecological factors are expected to influence spatial variation in infection risk by affecting the survival of free-living life stages outside the host and the abundance of intermediate gastropod hosts. Here, we investigate how ecology influenced the fine-scale distribution of these parasites in deer in Voyageurs National Park, Minnesota. Deer pellet groups (N = 295) were sampled for the presence of P. tenuis larvae and F. magna eggs. We found that deer were significantly more likely to be infected with P. tenuis in habitats with less upland deciduous forest and more upland mixed conifer forest and shrub, a pattern that mirrored microhabitat differences in gastropod abundances. Deer were also more likely to be infected with F. magna in areas with more marshland, specifically rooted-floating aquatic marshes (RFAMs). The environment played a larger role than deer density in determining spatial patterns of infection for both parasites, highlighting the importance of considering ecological factors on all stages of a parasite's life cycle in order to understand its occurrence within the definitive host. PMID:25498206

  5. The ultrastructural characterization of the tegument of Clonorchis sinensis (Cobbold, 1875) cercaria.

    PubMed

    Fujino, T; Ishii, Y; Choi, D W

    1979-11-01

    The tegumental ultrastructure of the cercaria of the liver fluke, Clonorchis sinensis (Cobbold, 1875), was studied by scanning and transmission electron microscopy. The body surface is almost encircled by many rows of regularly arranged spines. The tegumental syncytium of the body contains many rod-shaped dense granules and central electron-lucent bodies, neither of which are present in the tail tegument. There are four rows of hooked teeth and modified spines on the oral cone. These teeth are differentiated morphologically and probably functionally from the other body spines. Disc-shaped papillae with long or short cilia are distributed on the body in a bilaterally symmetrical pattern dorsally and ventrally. There are 30 to 37 papillae with much longer cilia laterally. Four pairs of papillae were found on the tail. From their structure and location these papillae appear to have a mainly tango- or rheoreceptive function. Another type of sheathed papillae is situated around the oral sucker. The cuticular tegument is expanded laterally at the base of the tail, forming a characteristic sac-like structure. PMID:394497

  6. ClonorESTdb: a comprehensive database for Clonorchis sinensis EST sequences

    PubMed Central

    2014-01-01

    Background Clonorchiasis, which is primarily caused by liver fluke (Platyhelminthes), is a fatal infectious disease that is mainly associated with bile duct malignancy and the subsequent development of cholangiocarcinoma. Thus, a genomic approach now represents an important step to further our knowledge of biology and the pathology of these parasites. The results of expressed sequence tags (ESTs) sequencing need to be well organized into databases to provide an integrated set of tools and functional information. Findings Here, the ClonorESTdb database represents a collection of Clonorchis sinensis ESTs that is intended as a resource for parasite functional genomics. A total of 55,736 successful EST sequences, which are cleaned and clustered into non-redundant 13,305 C. sinensis assembled EST sequences (6,497 clusters and 6,808 singletons), were obtained from three in-house prepared cDNA libraries of C. sinensis at different developmental stages. The assembled consensus sequences were annotated using the BLAST algorithm or/and hmm against NCBI NR, UniProt, KEGG and InterProScan. The ClonorESTdb database provides functional annotation, their expression profiles, tandem repeats and putative single nucleotide polymorphisms with utility tools such as local BLAST search and text retrieval. Conclusions This resource enables the researcher to identify and compare expression signatures under different biological stages and promotes ongoing parasite drug and vaccine development and biological research. Database URL: http://pathod.cdc.go.kr/clonorestdb/ PMID:24957044

  7. Inhibitory effect of essential oils of Allium sativum and Piper longum on spontaneous muscular activity of liver fluke, Fasciola gigantica.

    TOXLINE Toxicology Bibliographic Information

    Singh TU; Kumar D; Tandan SK; Mishra SK

    2009-12-01

    Effects of essential oil of Allium sativum (garlic) and Piper longum (Indian long pepper) were evaluated on muscular activity of whole Fasciola gigantica and its strip preparation. The whole flukes and longitudinal strip preparations of the flukes were isometrically mounted to record the spontaneous muscular activity (SMA) and to evaluate effects of cumulative doses (0.1, 0.3, 1.0 and 3.0mg/ml) of the plant essential oils. Whole flukes and the strip preparations exhibited continuous SMA without any significant difference in its baseline tension, frequency and amplitude for 2h. Essential oil of A. sativum produced significant reduction in the frequency and the amplitude of the SMA of whole fluke at 1 and 3mg/ml concentrations. It caused complete paralysis of the fluke after 15 min of administration of 3mg/ml concentration. Similar to whole fluke, essential oil of A. sativum (3mg/ml) also produced flaccid paralysis in the strip preparations of the flukes. Essential oil of P. longum firstly induced marked excitatory effect and then there was flaccid paralysis of the whole fluke following 15 min exposure at 3mg/ml concentration. Complete flaccid paralysis of the strip preparation was also ensued after 15 min of administration of 3mg/ml concentration of P. longum. In both the essential oils, the whole fluke and strip preparations did not recover from paralysis following 2-3 washes. In conclusion, the observations demonstrated irreversible paralytic effect of essential oils of A. sativum and P. longum on F. giganticain vitro which might possibly help to developing herbal-based anthelmintic.

  8. Inhibitory effect of essential oils of Allium sativum and Piper longum on spontaneous muscular activity of liver fluke, Fasciola gigantica.

    PubMed

    Singh, Thakur Uttam; Kumar, Dinesh; Tandan, Surendra Kumar; Mishra, Santosh Kumar

    2009-12-01

    Effects of essential oil of Allium sativum (garlic) and Piper longum (Indian long pepper) were evaluated on muscular activity of whole Fasciola gigantica and its strip preparation. The whole flukes and longitudinal strip preparations of the flukes were isometrically mounted to record the spontaneous muscular activity (SMA) and to evaluate effects of cumulative doses (0.1, 0.3, 1.0 and 3.0mg/ml) of the plant essential oils. Whole flukes and the strip preparations exhibited continuous SMA without any significant difference in its baseline tension, frequency and amplitude for 2h. Essential oil of A. sativum produced significant reduction in the frequency and the amplitude of the SMA of whole fluke at 1 and 3mg/ml concentrations. It caused complete paralysis of the fluke after 15 min of administration of 3mg/ml concentration. Similar to whole fluke, essential oil of A. sativum (3mg/ml) also produced flaccid paralysis in the strip preparations of the flukes. Essential oil of P. longum firstly induced marked excitatory effect and then there was flaccid paralysis of the whole fluke following 15 min exposure at 3mg/ml concentration. Complete flaccid paralysis of the strip preparation was also ensued after 15 min of administration of 3mg/ml concentration of P. longum. In both the essential oils, the whole fluke and strip preparations did not recover from paralysis following 2-3 washes. In conclusion, the observations demonstrated irreversible paralytic effect of essential oils of A. sativum and P. longum on F. giganticain vitro which might possibly help to developing herbal-based anthelmintic. PMID:19679128

  9. Pharmacological and morphological characteristics of the muscular system of the giant liver fluke (Fascioloides magna - Bassi 1875).

    PubMed

    Trailović, Saša M; Marinković, Darko; Trailović, Jelena Nedeljković; Milovanović, Mirjana; Marjanović, Djordje S; Aničić, Milan R

    2015-12-01

    Motility is required for feeding, reproduction and maintenance of the fluke in the host's liver. According to that, the neuromuscular system can be an attractive drugable target for chemotherapy. Musculature of the Fascioloides magna is organized into three layers, an outer circular layer, beneath this layer the longitudinal layer, and third, the oblique, or diagonal layer underlies the longitudinal layer. In our study, the administration of atropine or caffeine did not cause classic muscle contractions of F. magna muscle strips. However, the Electrical Field Stimulation (EFS) induced stable and repeatable contractions, which enabled us to examine their sensitivity to the various substances. Acetylcholine (ACh) (300 μM and 1 mM), caused only a slight relaxation, without affecting the amplitude of spontaneous contractions or the amplitude of contractions induced by EFS. Contrary to that, atropine (100 μM) caused a significant increase in the basal tone and an increase of EFS-induced contractions. If acetylcholine is an inhibitory neurotransmitter in trematodes, the described effects of atropine are achieved by the blockade of inhibitory neurotransmission. On the other hand, with respect to the process of excitation-contraction coupling, the plant alkaloid ryanodine (30 μM) significantly reduced the basal tone, as well as EFS-induced contractions of F. magna muscle strips. Ryanodine inhibited the potentiating effect of atropine on the basal tone and contractions caused by EFS, which indicates that the contractile effect of atropine is dependent on Ca(++) release from intracellular stores. Caffeine (500 μM) caused relaxation of fluke muscle strips and at the same time significantly enhanced the EFS-induced contractions. Both effects of caffeine can be explained by entry of extracellular Ca(++) into muscle cells. The muscle contractility of F. magna depends both on the entry of extracellular calcium, and calcium release from intracellular stores, which are under the control of RyRs. Our results also suggest that antitrematodal drugs could potentially be developed from substances with selective anti-cholinergic activity. PMID:26429130

  10. Comparative proteomics of excretory-secretory proteins released by the liver fluke Fasciola hepatica in sheep host bile and during in vitro culture ex host.

    PubMed

    Morphew, Russell M; Wright, Hazel A; LaCourse, E James; Woods, Debra J; Brophy, Peter M

    2007-06-01

    Livestock infection by the parasitic fluke Fasciola hepatica causes major economic losses worldwide. The excretory-secretory (ES) products produced by F. hepatica are key players in understanding the host-parasite interaction and offer targets for chemo- and immunotherapy. For the first time, subproteomics has been used to compare ES products produced by adult F. hepatica in vivo, within ovine host bile, with classical ex host in vitro ES methods. Only cathepsin L proteases from F. hepatica were identified in our ovine host bile preparations. Several host proteins were also identified including albumin and enolase with host trypsin inhibitor complex identified as a potential biomarker for F. hepatica infection. Time course in vitro analysis confirmed cathepsin L proteases as the major constituents of the in vitro ES proteome. In addition, detoxification proteins (glutathione transferase and fatty acid-binding protein), actin, and the glycolytic enzymes enolase and glyceraldehyde-3-phosphate dehydrogenase were all identified in vitro. Western blotting of in vitro and in vivo ES proteins showed only cathepsin L proteases were recognized by serum pooled from F. hepatica-infected animals. Other liver fluke proteins released during in vitro culture may be released into the host bile environment via natural shedding of the adult fluke tegument. These proteins may not have been detected during our in vivo analysis because of an increased bile turnover rate and may not be recognized by pooled liver fluke infection sera as they are only produced in adults. This study highlights the difficulties identifying authentic ES proteins ex host, and further confirms the potential of the cathepsin L proteases as therapy candidates. PMID:17308300

  11. Opisthorchis viverrini-like liver fluke in birds from Vietnam: morphological variability and rDNA/mtDNA sequence confirmation.

    PubMed

    Dao, T H; Nguyen, T G; Victor, B; Gabriël, S; Dorny, P

    2014-12-01

    Flukes were found in the bile ducts of domestic ducks (Anas platyrhynchos), necropsied in the Binh Dinh province of Central Vietnam. Following staining, morphological characteristics of the bird flukes were compatible with Opisthorchis viverrini, although some characteristics differed from those described in specimens collected from mammal hosts. Computation of the phylogenetic trees on the partial sequences of the second internal ribosomal spacer (ITS2) of the ribosomal DNA and cytochrome c oxidase subunit I (COI) markers of the mitochondrial DNA showed close similarity of the 'bird' Opisthorchis sp. with O. viverrini. We speculate that these bird flukes are O. viverrini that show intraspecies morphological and molecular variability compared to isolates from mammals. This demonstrates the complex epidemiological situation of opisthorchiasis in Vietnam and urges investigations on the potential of birds as a reservoir host of this zoonotic fluke. PMID:23721954

  12. Development of a TaqMan based real-time PCR assay for detection of Clonorchis sinensis DNA in human stool samples and fishes.

    PubMed

    Cai, Xian-Quan; Yu, Hai-Qiong; Bai, Jian-Shan; Tang, Jian-Dong; Hu, Xu-Chu; Chen, Ding-Hu; Zhang, Ren-Li; Chen, Mu-Xin; Ai, Lin; Zhu, Xing-Quan

    2012-03-01

    Clonorchiasis caused by the oriental liver fluke Clonorchis sinensis is a fish-borne zoonosis endemic in a number of countries. This article describes the development of a TaqMan based real-time PCR assay for detection of C. sinensis DNA in human feces and in fishes. Primers targeting the first internal transcribed spacer (ITS-1) sequence of the fluke were highly specific for C. sinensis, as evidenced by the negative amplification of closely related trematodes in the test with the exception of Opisthorchis viverrini. The detection limit of the assay was 1pg of purified genomic DNA, 5EPG (eggs per gram feces) or one metacercaria per gram fish filet. The assay was evaluated by testing 22 human fecal samples and 37 fish tissues microscopically determined beforehand, and the PCR results were highly in agreement with the microscopic results. This real-time PCR assay provides a useful tool for the sensitive detection of C. sinensis DNA in human stool and aquatic samples in China and other endemic countries where O. viverrini and Opisthorchis felineus are absent. PMID:21729765

  13. Liver Fluke Infection and Fish Consumption in Khon Kaen, Thailand: A Case Study on Negotiating the Middle Ground between Western Science and Eastern Culture

    NASA Astrophysics Data System (ADS)

    Samiphak, Sara

    This research investigates why typical strategies for promoting health, prolonging life, and preventing disease do not work in many communities. I use the liver fluke infection endemic in Khon Kaen, Thailand to explore the middle ground between Western science and Eastern culture. Prior work on the O.viverrini infection in Khon Kaen, Thailand has focused almost exclusively on developing effective medical treatment for the liver fluke infection. This dissertation employs a case study designed to explore the conditions that created and perpetuate the problem in the first place. In concrete terms, I analyze how the worldviews of local villagers shape their attitudes toward life (and death), which in turn determine if they engage in the high-risk behavior -- eating undercooked fish -- that makes them vulnerable to the infection. My research focuses on these people in-situ over a three-month period, and includes data from participant-observation, interviews, and video-recordings. This work seeks to illuminate how people's thinking and reasoning skills, and personal/cultural identities affect their abilities to learn and act on new health concepts. This potentially provides a window into future educational strategies in a complex world.

  14. Development and characterization of multiplex panels of polymorphic microsatellite loci in giant liver fluke Fascioloides magna (Trematoda: Fasciolidae), using next-generation sequencing approach.

    PubMed

    Minárik, Gabriel; Bazsalovicsová, Eva; Zvijáková, Ludmila; Stefka, Jan; Pálková, Lenka; Králová-Hromadová, Ivica

    2014-06-01

    The microsatellite markers were designed for the giant liver fluke, Fascioloides magna, veterinary important liver parasite of free-living and domestic ruminants. Due to its geographic distribution (five enzootic regions across USA and Canada, three permanent European foci) and invasive character, F. magna is an interesting model for population genetics. Out of 667 amplicon candidates generated after NGS, 118 provided the best resolution and were tested with PCR analysis. In total, 56 yielded PCR products of expected size and in 36 of them the declared repetitive motif was identified by Sanger sequencing. After fragment analysis, 12 loci were proved to be polymorphic in individuals from one tested European and four North American populations. These loci were selected for setup of multiplex STR assays and utilized in genotyping of larger sample cohort. The outputs of statistical analyses indicate further global application of 11 conclusive loci in population genetics of the parasite. PMID:24959976

  15. Cytokine/chemokine secretion and proteomic identification of upregulated annexin A1 from peripheral blood mononuclear cells cocultured with the liver fluke Opisthorchis viverrini.

    PubMed

    Hongsrichan, Nuttanan; Intuyod, Kitti; Pinlaor, Porntip; Khoontawad, Jarinya; Yongvanit, Puangrat; Wongkham, Chaisiri; Roytrakul, Sittiruk; Pinlaor, Somchai

    2014-05-01

    We investigated the cytokine/chemokine secretions and alteration of protein expression from peripheral blood mononuclear cells (PBMCs) cocultured with adult liver flukes (Opisthorchis viverrini) for 6 to 24 h. PBMC-derived proteins were identified by two-dimensional electrophoresis and mass spectrometry, and the cytokines/chemokines in the supernatant were assessed using a cytokine array. Exposure to O. viverrini induced increases in secretion of proinflammatory cytokines, costimulating protein, adhesion molecules, and chemotactic chemokines relative to untreated controls. In contrast, secretion of the CD40 ligand, interleukin 16, and macrophage inflammatory protein 1β decreased. Proteomic analysis revealed that expression of 48 proteins was significantly altered in PBMCs stimulated with O. viverrini. Annexin A1 (ANXA1) was selected for further study, and immunoblotting showed upregulation of ANXA1 expression in PBMCs after 12 and 24 h coculture with liver flukes. In an in vivo study, transcription and translation of ANXA1 significantly increased in livers of hamsters infected with O. viverrini at 21 days and from 3 months onwards compared to normal controls. Interestingly, immunohistochemistry revealed that ANXA1 was present not only in the cytoplasm of inflammatory cells but also in the cytoplasm of cholangiocytes, which are in close contact with the parasite and its excretory/secretory products in the biliary system. Expression of ANXA1 increased with time concomitant with bile duct enlargement, bile duct formation, and epithelial cell proliferation. In conclusion, several cytokines/chemokines secreted by PBMCs and upregulation of ANXA1 in PBMCs and biliary epithelial cells might have a role in host defense against O. viverrini infection and tissue resolution of inflammation. PMID:24614660

  16. Molecular characterization of an α-N-acetylgalactosaminidase from Clonorchis sinensis.

    PubMed

    Lee, Myoung-Ro; Yoo, Won Gi; Kim, Yu-Jung; Kim, Dae-Won; Cho, Shin-Hyeong; Hwang, Kwang Yeon; Ju, Jung-Won; Lee, Won-Ja

    2012-11-01

    The α-N-acetylgalactosaminidase (α-NAGAL) is an exoglycosidase that selectively cleaves terminal α-linked N-acetylgalactosamines from a variety of sugar chains. A complementary DNA (cDNA) clone encoding a novel Clonorchis sinensis α-NAGAL (Cs-α-NAGAL) was identified in the expressed sequence tags database of the adult C. sinensis liver fluke. The complete coding sequence was 1,308 bp long and encoded a 436-residue protein. The selected glycosidase was manually curated as α-NAGAL (EC 3.2.1.49) based on a composite bioinformatics analysis including a search for orthologues, comparative structure modeling, and the generation of a phylogenetic tree. One orthologue of Cs-α-NAGAL was the Rattus norvegicus α-NAGAL (accession number: NP_001012120) that does not exist in C. sinensis. Cs-α-NAGAL belongs to the GH27 family and the GH-D clan. A phylogenetic analysis revealed that the GH27 family of Cs-α-NAGAL was distinct from GH31 and GH36 within the GH-D clan. The putative 3D structure of Cs-α-NAGAL was built using SWISS-MODEL with a Gallus gallus α-NAGAL template (PDB code 1ktb chain A); this model demonstrated the superimposition of a TIM barrel fold (α/β) structure and substrate binding pocket. Cs-α-NAGAL transcripts were detected in the adult worm and egg cDNA libraries of C. sinensis but not in the metacercaria. Recombinant Cs-α-NAGAL (rCs-α-NAGAL) was expressed in Escherichia coli, and the purified rCs-α-NAGAL was recognized specifically by the C. sinensis-infected human sera. This is the first report of an α-NAGAL protein in the Trematode class, suggesting that it is a potential diagnostic or vaccine candidate with strong antigenicity. PMID:22926676

  17. A tegument-specific venom allergen-like protein of Clonorchis sinensis.

    PubMed

    Woo, Hea Sun; Kim, Tae Yun; Sohn, Woon-Mok; Yong, Tai-Soon

    2015-01-01

    Venom allergen-like (VAL) proteins, members of the SCP/TAPS (sperm coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, have been reported from several parasitic helminths. As little is known about their biological functions, a VAL protein of the Chinese liver fluke Clonorchis sinensis was cloned and characterized. A complementary DNA (cDNA) encoding a 25-kDa protein was identified from an EST database of C. sinensis. A BLAST search revealed that the protein shares 46% sequence identity with Schistosoma mansoni VAL 13 protein, and thus, the protein was named CsVAL13. Multiple sequence alignment indicated that the SCP/TAPS domain of CsVAL13 shares 39-46% sequence identity with VAL proteins from parasitic helminths. His and Tyr, which help to stabilize protein structure, were highly conserved across the VAL protein sequences. Phylogenetic analysis showed that the SCP/TAPS domain of the CsVAL13 sequence clusters together with other group 2 VAL protein sequences. In the homology-modeled structure of CsVAL13, an α-β-α sandwich and residues for a putative active site were highly conserved. Immune sera were obtained from BALB/c mice immunized with the recombinant CsVAL13 protein. Immunohistochemical localization using the immune sera revealed that CsVAL13 was distributed mainly in the tegument and intrauterine eggs of adult C. sinensis. These findings suggest that CsVAL13 may be involved in host-parasite interactions and immune stimulation on the surrounding host environments. PMID:25403376

  18. Oral delivery of Bacillus subtilis spore expressing enolase of Clonorchis sinensis in rat model: induce systemic and local mucosal immune responses and has no side effect on liver function.

    PubMed

    Yu, Jinyun; Chen, Tingjin; Xie, Zhizhi; Liang, Pei; Qu, Honglin; Shang, Mei; Mao, Qiang; Ning, Dan; Tang, Zeli; Shi, Mengchen; Zhou, Lina; Huang, Yan; Yu, Xinbing

    2015-07-01

    Caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensis, human clonorchiasis remains a major public health problem in China. In previous study, we had expressed enolase from C. sinensis (CsENO) on the surface of Bacillus subtilis spore and the recombinant spore induced a pronounced protection in terms of reduced worm burden and eggs per gram feces, suggesting B. subtilis spore as an ideal vehicle for antigen delivery by oral treatment and CsENO as a promising vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgG and IgA levels both in serum and in intestinal mucus from rats orally administrated with B. subtilis spore surface expressing CsENO by ELISA. Lysozyme levels in serum and in intestinal mucus were analyzed too. In addition, IgA-secreting cells in intestine epithelium of the rats were detected by immunohistochemistry assay. The intestinal villi lengths of duodenum, jejunum, and ileum were also measured. Rats orally treated with B. subtilis spore or normal saline were used as controls. Our results showed that, compared with the control groups, oral administration of B. subtilis spore expressing CsENO induced both systemic and local mucosal immune response. The recombinant spores also enhanced non-specific immune response in rats. The spores had no side effect on liver function. Moreover, it might facilitate food utilization and digestion of the rats. Our work will pave the way to clarify the involved mechanisms of protective efficacy elicited by B. subtilis spore expressing CsENO and encourage us to carry out more assessment trails of the oral treated spore to develop vaccine against clonorchiasis. PMID:25877387

  19. High Prevalence of the Liver Fluke Amphimerus sp. in Domestic Cats and Dogs in an Area for Human Amphimeriasis in Ecuador

    PubMed Central

    Calvopiña, Manuel; Cevallos, William; Atherton, Richard; Saunders, Matthew; Small, Alexander; Kumazawa, Hideo; Sugiyama, Hiromu

    2015-01-01

    Background Amphimerus sp. is a liver fluke which recently has been shown to have a high prevalence of infection among an indigenous group, Chachi, who reside in a tropical rainforest in the northwestern region of Ecuador. Since it is unknown which animals can act as a reservoir and/or definitive hosts for Amphimerus sp. in this endemic area, a study was done to determine the prevalence of infection in domestic cats and dogs. This information is important to understand the epidemiology, life cycle and control of this parasite. Methodology/Findings In July 2012, three Chachi communities located on Rio Cayapas, province of Esmeraldas, were surveyed. A total of 89 of the 109 registered households participated in the study. Of the 27 cats and 43 dogs found residing in the communities, stool samples were collected from 14 cats and 31 dogs (total of 45 animals) and examined microscopically for the presence of Amphimerus eggs. The prevalence of infection was 71.4% in cats and 38.7% in dogs, with similar rates of infection in all three communities. Significantly more cats were infected than dogs (p = 0.042). Conclusions/Significance The data show a high rate of Amphimerus sp. infection in domestic cats and dogs residing in Chachi communities. It can be concluded that these animals act as definitive and reservoir hosts for this liver fluke and that amphimeriasis is a zoonotic disease. These findings provide important epidemiological data which will aid in the development and implementation of control strategies against the transmission of Amphimerus. PMID:25647171

  20. Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B

    PubMed Central

    Sripa, Jittiyawadee; Laha, Thewarach; To, Joyce; Brindley, Paul J.; Sripa, Banchob; Kaewkes, Sasithorn; Dalton, John P.; Robinson, Mark W.

    2010-01-01

    Summary Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that auto-catalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot auto-catalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma. PMID:20070308

  1. Excretory/secretory products of the carcinogenic liver fluke are endocytosed by human cholangiocytes and drive cell proliferation and IL6 production.

    PubMed

    Chaiyadet, Sujittra; Smout, Michael; Johnson, Michael; Whitchurch, Cynthia; Turnbull, Lynne; Kaewkes, Sasithorn; Sotillo, Javier; Loukas, Alex; Sripa, Banchob

    2015-10-01

    Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products (OvES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south-eastern Asia. PMID:26187786

  2. Charge modification at conserved positively charged residues of fatty acid binding protein (FABP) from the giant liver fluke Fasciola gigantica: its effect on oligomerization and binding properties.

    PubMed

    Janvilisri, Tavan; Likitponrak, Wichai; Chunchob, Supatra; Grams, Rudi; Vichasri-Grams, Suksiri

    2007-11-01

    Fatty acid binding proteins (FABPs) are capable of binding hydrophobic ligands with high affinity; thereby facilitating the cellular uptake and intracellular trafficking of fatty acids. In this study, functional characteristics of a cytoplasmic FABP from the giant liver fluke Fasciola gigantica (FgFABP) were determined. Binding of a fluorescent fatty acid analogue 11-[[5-dimethy aminonaphtalene-1-sulphonyl] amino] undecanoic acid (DAUDA) to FgFABP resulted in changes in the emission spectrum. The optimal excitation wavelength and maximum emission of fluorescence for binding activities with DAUDA were 350 nm and 550 nm, respectively. The binding activity for DAUDA was determined from titration experiments and revealed a Kd value of 2.95+/-0.54 microM. Furthermore, we found that cross-linking profile of FgFABP with dithiobis-(succinimidylpropionate) (DSP) in the presence of DAUDA resulted in increased formation of higher-ordered oligomers compared to that in the absence of DAUDA. We also replaced five highly conserved positively charged residues (K9, K58, K91, R107 and K131) with alanine and studied their oligomerization and binding properties of the modified FgFABPs. The obtained data demonstrate that these residues do not appear to be involved in oligomerization. However, the K58A and R107A substitutions exhibited a reduction in binding affinities. K91A and R107A revealed an increase in maximal specific binding. PMID:17594059

  3. Expression, refolding and purification of Ov-GRN-1, a granulin-like growth factor from the carcinogenic liver fluke, that causes proliferation of mammalian host cells.

    PubMed

    Smout, Michael J; Mulvenna, Jason P; Jones, Malcolm K; Loukas, Alex

    2011-10-01

    Granulins (GRNs) are potent growth factors that are upregulated in many aggressive cancers from a wide range of organs. GRNs form tight, disulphide bonded, beta hairpin stacks, making them difficult to express in recombinant form. We recently described Ov-GRN-1, a GRN family member secreted by the carcinogenic liver fluke of humans, Opisthorchis viverrini, and showed that recombinant Ov-GRN-1 expressed and refolded from Escherichia coli caused proliferation of mammalian cell lines at nanomolar concentrations. We now report on an optimized method to express and purify monomeric Ov-GRN-1 in E. coli using a straightforward and scalable purification and refolding process. Purified monomeric protein caused proliferation at nanomolar concentrations of cancerous and non-cancerous cell lines derived from human bile duct tissue. The expression and purification method we describe herein will serve as a backbone upon which to develop expression and purification processes for recombinant GRNs from other organisms, accelerating research on this intriguing family of proteins. PMID:21757010

  4. Identity of rumen fluke in deer.

    PubMed

    O'Toole, Ailis; Browne, John A; Hogan, Sean; Bassière, Thomas; DeWaal, Theo; Mulcahy, Grace; Zintl, Annetta

    2014-11-01

    As evidence is growing that in many temperate areas paramphistome infections are becoming more common and widespread, this study was undertaken to determine the role of deer as reservoirs for rumen fluke infections in livestock. A total of 144 deer faecal samples (88 from fallow deer, 32 from red deer and 24 samples from sika, sika/red deer hybrids) were screened for the presence of fluke eggs. Based on the ITS-2 rDNA locus plus flanking 5.8S and 28S sequences (ITS-2+), fluke eggs were identified to species level. Our results indicate that, of the 3 deer species, fallow deer had the highest fluke infection rates. Two rumen fluke species, Calicophoron daubneyi and Paramphistomum leydeni, with morphologically distinct eggs, were identified. Concurrent infections of the two paramphistome species and liver fluke, Fasciola hepatica, were common. Considering the comparatively low egg burdens observed in this study, it is unlikely that deer represent a significant source of infection for Irish livestock. PMID:25127736

  5. Accumulation of miscoding etheno-DNA adducts and highly expressed DNA repair during liver fluke-induced cholangiocarcinogenesis in hamsters.

    PubMed

    Dechakhamphu, Somkid; Pinlaor, Somchai; Sitthithaworn, Paiboon; Bartsch, Helmut; Yongvanit, Puangrat

    2010-09-10

    Infection by Opisthorchis viverrini, a risk factor for cholangiocarcinoma (CCA) may act through chronic inflammation, oxidative stress and lipid peroxidation (LPO)-related damage and growth stimuli. 1,N6-etheno-2'-deoxyadenosine (epsilondA), and 3,N4-etheno-2'-deoxycytidine (epsilondC), markers for LPO-derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients. In order to investigate tissue specificity etheno adducts were measured in a cholangiocarcinogenesis model, in O. viverrini-infected hamsters that had received N-nitrosodimethylamine (NDMA, 12.5 ppm in dw) for 2 months. epsilondA- and epsilondC-levels were analyzed in paraffin-embedded liver sections by a novel immunohistochemical method, from 21 up to 180 days post-O. viverrini-infection. In inflamed areas of the liver, etheno adducts were localized in the nuclei of inflammatory cells and in the epithelial lining of the bile duct. Semi-quantitative image analysis showed higher adduct levels in the liver of O. viverrini-infected hamsters, treated with or w/o NDMA when compared with untreated controls. Levels were found highest in the liver of O. viverrini-infected plus NDMA-treated hamsters. Adducts increased in an age-dependent manner from O. viverrini-infection until CCA development. Increased adduct formation paralleled histopathological changes in plasma alkaline phosphatase (ALP) activity, bile duct hyperplasia, dysplasia, precancerous lesions, and CCA appearance. Also elevated expression of alkyladenine DNA glycosylase (AAG), which excises 1,N6-ethenoadenine (epsilonA) was linked to higher adduct formation, suggesting imbalanced repair. Our results implicate accumulation of inflammation-related, promutagenic DNA damage in target tissue and possibly imbalanced repair in the onset of cholangiocarcinogenesis. PMID:20541562

  6. RNA-Seq Reveals Infection-Induced Gene Expression Changes in the Snail Intermediate Host of the Carcinogenic Liver Fluke, Opisthorchis viverrini

    PubMed Central

    Prasopdee, Sattrachai; Sotillo, Javier; Tesana, Smarn; Laha, Thewarach; Kulsantiwong, Jutharat; Nolan, Matthew J.

    2014-01-01

    Background Bithynia siamensis goniomphalos is the snail intermediate host of the liver fluke, Opisthorchis viverrini, the leading cause of cholangiocarcinoma (CCA) in the Greater Mekong sub-region of Thailand. Despite the severe public health impact of Opisthorchis-induced CCA, knowledge of the molecular interactions occurring between the parasite and its snail intermediate host is scant. The examination of differences in gene expression profiling between uninfected and O. viverrini-infected B. siamensis goniomphalos could provide clues on fundamental pathways involved in the regulation of snail-parasite interplay. Methodology/Principal Findings Using high-throughput (Illumina) sequencing and extensive bioinformatic analyses, we characterized the transcriptomes of uninfected and O. viverrini-infected B. siamensis goniomphalos. Comparative analyses of gene expression profiling allowed the identification of 7,655 differentially expressed genes (DEGs), associated to 43 distinct biological pathways, including pathways associated with immune defense mechanisms against parasites. Amongst the DEGs with immune functions, transcripts encoding distinct proteases displayed the highest down-regulation in Bithynia specimens infected by O. viverrini; conversely, transcription of genes encoding heat-shock proteins and actins was significantly up-regulated in parasite-infected snails when compared to the uninfected counterparts. Conclusions/Significance The present study lays the foundation for functional studies of genes and gene products potentially involved in immune-molecular mechanisms implicated in the ability of the parasite to successfully colonize its snail intermediate host. The annotated dataset provided herein represents a ready-to-use molecular resource for the discovery of molecular pathways underlying susceptibility and resistance mechanisms of B. siamensis goniomphalos to O. viverrini and for comparative analyses with pulmonate snail intermediate hosts of other platyhelminths including schistosomes. PMID:24676090

  7. Fasciola hepatica - monitoring the milky way? The use of tank milk for liver fluke monitoring in dairy herds as base for treatment strategies.

    PubMed

    Duscher, Ruth; Duscher, Georg; Hofer, Johannes; Tichy, Alexander; Prosl, Heinrich; Joachim, Anja

    2011-06-10

    In this study 595 lactating cows originating from 31 carinthian farms were investigated in accordance of liver fluke infection using individual and tank milk as well as individual blood and faecal samples. Two commercial ELISAs were used to test the milk and blood serum, and the results were compared with coproscopy and a commercial copro-antigen ELISA. Receiver operating characteristics (ROC) and two-graph operating characteristics (TG ROC) of tank milk results were conducted based on the individual milk to determine the minimum reliable in-herd antibody prevalence for the predominant condition in the investigation area. In 17.8% of the examined individuals located in 64.5% of the farms eggs were detected by coproscopy. The copro-antigen ELISA delivered 13.4% positive individuals from 54.8% of the farms. The milk ELISAs showed 42.7% (Euroclone) and 44.2% (Pourquier) positive cows on 90.3% of the farms. The blood samples were positive in 43% (Euroclone) and 45.2% (Pourquier) of the individuals from 90.3% to 96.8% of the herds, respectively. Based on the milk and the blood an average in-herd prevalence of 30-45% can be assumed. The serum and milk samples delivered correlating results with kappa values between 0.94 and 0.97, whereas the coproscopy and copro-antigen ELISA did not correlate well with the ELISA results. The two different ELISA tests highly correlated on individual and on herd level. Both showed a reliable minimum in-herd prevalence of ∼20%, meaning that one fifth of the individuals in a herd have to be positive to obtain a positive bulk tank milk result. In the investigated area a higher in-herd prevalence is expected, therefore the tank milk is useful as a monitoring tool and can be used as a basis for intervention strategies. PMID:21334811

  8. Lipid peroxidation and etheno DNA adducts in white blood cells of liver fluke-infected patients: protection by plasma alpha-tocopherol and praziquantel.

    PubMed

    Dechakhamphu, Somkid; Pinlaor, Somchai; Sitthithaworn, Paiboon; Nair, Jagadeesan; Bartsch, Helmut; Yongvanit, Puangrat

    2010-01-01

    Chronic infection by the liver fluke Opisthorchis viverrini is a strong risk factor for cholangiocarcinoma. To clarify the involvement of oxidative stress and lipid peroxidation-derived DNA damage, etheno (epsilon)-DNA adducts (epsilondA, epsilondC) in WBC and plasma alpha-tocopherol were measured in samples collected from O. viverrini-infected Thai patients (n = 50) and healthy noninfected volunteers (n = 20). epsilondA and epsilondC levels were three to five times higher (P < 0.001) in infected patients than in controls; O. viverrini infection also increased two to three times in the plasma inflammatory indicators, 8-isoprostane, malondialdehyde, and nitrate/nitrite. Mean plasma alpha-tocopherol levels were two times lower in patients than in healthy controls (P < 0.001). Two months after a single dose to infected patients of the antiparasitic drug praziquantel, epsilondA and epsilondC levels in WBC were decreased to control level (P < 0.03); plasma 8-isoprostane, malondialdehyde, nitrate/nitrite, and alkaline phosphatase (ALP) were concomitantly lowered. epsilondA and epsilondC levels in WBC were positively correlated with plasma 8-isoprostane, malondialdehyde, and nitrate/nitrite levels and ALP activity, whereas plasma alpha-tocopherol levels showed inverse correlations. We conclude that chronic O.viverrini infection induces an accumulation of lipid peroxidation-derived DNA damage through oxidative/nitrative stress, which is lowered by the plasma alpha-tocopherol and by antiparasitic drug therapy. Etheno adducts in WBC and urine should be explored as a risk marker for opisthorchiasis-related cholangiocarcinoma, and to assess the efficacy of preventive and therapeutic interventions. PMID:20056652

  9. Fasciola hepatica phenotypic characterization in Andean human endemic areas: valley versus altiplanic patterns analysed in liver flukes from sheep from Cajamarca and Mantaro, Peru.

    PubMed

    Valero, M Adela; Perez-Crespo, Ignácio; Khoubbane, Messaoud; Artigas, Patricio; Panova, Miroslava; Ortiz, Pedro; Maco, Vicente; Espinoza, José R; Mas-Coma, Santiago

    2012-03-01

    Fascioliasis is a zoonotic parasitic disease caused by Fasciola hepatica and Fasciola gigantica. Of both species, F. hepatica is the only one described in the Americas, mainly transmitted by lymnaeid snail vectors of the Galba/Fossaria group. Human fascioliasis endemic areas are mainly located in high altitude areas of Andean countries. Given the necessity to characterize F. hepatica populations involved, the phenotypic features of fasciolid adults infecting sheep present in human fascioliasis endemic areas were analysed in the Cajamarca Valley and Mantaro Valley (valley transmission patterns) and the northern Bolivian Altiplano (altiplanic transmission pattern). A computer image analysis system (CIAS) was applied on the basis of standardized measurements. The aforementioned highland populations were compared to standard lowland natural and experimental populations of European origin. Liver fluke size was studied by multivariate analyses. Two phenotypic patterns could be distinguished in F. hepatica adult size: the valley pattern (Cajamarca and Mantaro, Peru) and the altiplanic pattern (northern Altiplano, Bolivia). Results showed that the Andean valley population and European standard populations presented a phenotypic homogeneity. The Altiplano population showed a large size range with a pronouncedly lower minimum size indicating that uterus gravidity is reached at a smaller size than in valley populations. The results of this study demonstrate that there is no apparent relationship between the shape of fasciolid adults with regard to altitudinal difference or geographical origin and that allometry-free shape appears as a more stable trait than size in fasciolid species. Results are analysed in terms of intensity/crowding effect aspects and permanent/seasonal transmission characteristics. PMID:22285769

  10. Immunosuppressive prednisolone enhances early cholangiocarcinoma in Syrian hamsters with liver fluke infection and administration of N-nitrosodimethylamine.

    PubMed

    Juasook, Amornrat; Boonmars, Thidarut; Wu, Zhiliang; Loilome, Watcharin; Veteewuthacharn, Kulathida; Namwat, Nissana; Sudsarn, Pakkayanee; Wonkchalee, Orasa; Sriraj, Pranee; Aukkanimart, Ratchadawan

    2013-01-01

    Chronic infection with Opisthorchis viverrini for many years has been associated with the development of hepatobiliary diseases including cholangiocarcinoma. It is well known that inflammation is a key component of the tumor microenvironment, and that chronic inflammation plays an important role in tumorigenesis. Therefore, in this study cholangiocarcinogenesis was induced in Syrian hamsters in order to observe the cancer-related inflammation. The Syrian hamsters were divided into 5 groups: uninfected controls; normal Syrian hamsters infected with O. viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini (OVis); normal Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers were later observed for gross pathology and histopathological changes; COX2 was analyzed by immunohistochemical staining. We found a decreased number of inflammatory cells surrounding the hepatic bile duct in the OVis group, but not in the OV and CCAis groups. However, in the CCAis group (with suppressed immunity) early appearance and greater severity of cholangiocarcinoma were observed; gross pathological examination revealed many cancer nodularities on the liver surface, and histopathological studies showed the presence of cancer cells, findings which correlated with the predominant expression of COX2. The present study suggests that host immune responses are intended to ameliorate pathology, and they are also crucially associated with pathogenesis in O. viverrini infection; the unbalancing of host immunity may enhance cancer-related inflammation. PMID:22851165

  11. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    SciTech Connect

    Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja; Park, Jin Wook; Park, Yeong-Min; Lee, Sang Eun

    2011-04-22

    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and helminth infection.

  12. Effectiveness of a Health Educational Program Based on Self-Efficacy and Social Support for Preventing Liver Fluke Infection in Rural People of Surin Province, Thailand.

    PubMed

    Kaewpitoon, Soraya J; Thanapatto, Sirisuda; Nuathong, Wimonya; Rujirakul, Ratana; Wakkuwattapong, Parichart; Norkaew, Jun; Kujapun, Jirawoot; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

    2016-01-01

    Opisthorchiasis is a major problem in Thailand particularly in northeast region which also has a high incidence of cholangiocarcinomas. Since health modification is needed, this quasi-experimental study aimed to assess the effectiveness of a health education program based on self-efficacy and social support in Tha Tum district, Surin province, Thailand. A total of 70 participants were purposive selected with a history of opisthorchiasis. Participants were divided into experimental and control groups, each with 35 subjects. The experimental group received a health education program composed of: (1) knowledge improvement, lectured with multimedia, demonstration, brochure, and handbook; (2) group discussion about their health beliefs, sharing their ideas and experience; and (3) social support from village health volunteers (VHV), heads of villages (HV), friends, and members of families, and public health officer (PHO). Follow-up was by PHO/VHV/HV, with provision of certificates and flasg for household that did not eat raw fish. Data were collected by predesigned questionnaires after implementation of the program for 3 months. Comparative data was analyzed by paired simple t-test and independent t-test. The results revealed that the experimental group had mean score of knowledge higher more than before the experiment (mean difference=3.1, t=3.915, 95%CI-3.3, -1.8 p-value=0.001), and the control group (mean difference=2.5, t=4.196, 95%CI=1.4, 3.6, p-value=0.001) with statistical significance. The mean scores of practice were higher than before the experiment (mean difference=4.6, t=4.331, 95%CI-5.3, -3.1, p-value=0.001), and control group (mean difference=4.4, t=6.142, 95%CI=4.2, 7.9, p-value=0.001) . The mean scores of perceived susceptibility and perceived severity of opisthorchiasis, al well as perceived benefits and perceived barriers to prevention of opisthorchiasis, were also higher than before the experiment and in the control group (p-value <0.001). In conclusion, this was a successful health education program for liver fluke avoidance. Therefore, it may useful for further behavior modification in the other epidemic areas. PMID:27039733

  13. The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice

    PubMed Central

    Hua, Hui; Li, Bo; Zhang, Bo; Yu, Qian; Li, Xiang-Yang; Liu, Ying; Pan, Wei; Liu, Xiang-Ye; Tang, Ren-Xian; Zheng, Kui-Yang

    2015-01-01

    Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis. PMID:26599407

  14. Immunization and challenge shown by hamsters infected with Opisthorchis viverrini following exposure to gamma-irradiated metacercariae of this carcinogenic liver fluke.

    PubMed

    Papatpremsiri, A; Junpue, P; Loukas, A; Brindley, P J; Bethony, J M; Sripa, B; Laha, T

    2016-01-01

    Here we report findings to optimize and standardize conditions to attenuate metacercariae of Opisthorchis viverrini by ionizing radiation to elicit protective immune responses to challenge infection. Metacercariae were gamma-irradiated and the ability of irradiated metacercariae to prevent patent infection of challenge metacercariae in hamsters was determined, as well as their ability to induce a host antibody response. Metacercariae irradiated in a dose-dependent manner, with 3, 5, 10, 12, 20, 25 and 50 Gray, were used to infect Syrian golden hamsters by stomach gavage to ascertain the effect of irradiation on ability of the worms to establish infection. In addition, other hamsters were infected with metacercariae irradiated with 20-50 Gray, followed by challenge with intact/wild-type (non-irradiated) metacercariae to determine the protective effect as established by the numbers of adult flukes, eggs of O. viverrini in hamster faeces and anti-O. viverrini antibody titres. Significantly fewer worms were recovered from hamsters immunized with metacercariae irradiated at 20, 25 and 50 Gray than from control hamsters infected with intact metacercariae or 0 Gray, and the worms showed damaged reproductive organs. Faecal egg numbers were decreased significantly in hamsters immunized with 25 and 50 Gray metacercariae of O. viverrini. Moreover, hamsters administered metacercariae that were protected elicited a robust, specific anti-fluke immunoglobulin G response compared to control hamsters, suggesting a role for antibody in protection elicited by radiation-attenuated metacercariae. PMID:25315797

  15. Liver fluke control on sheep farms in Northern Ireland: A survey of changing management practices in relation to disease prevalence and perceived triclabendazole resistance.

    PubMed

    McMahon, C; Edgar, H W J; Hanna, R E B; Ellison, S E; Flanagan, A M; McCoy, M; Kajugu, P-E; Gordon, A W; Irwin, D; Barley, J E; Malone, F E; Brennan, G P; Fairweather, I

    2016-01-30

    Reports of resistance to triclabendazole (TCBZ) among fluke populations have increased in recent years. Allied to this, there has been a rise in the prevalence of the disease, which has been linked to climate change. Results from questionnaire surveys conducted in Northern Ireland (NI) in 2005 (covering the years 1999-2004) and 2011 (covering the years 2008-2011) have provided an opportunity to examine the extent to which fluke control practices have changed over a prolonged time-frame, in light of these changes. A number of differences were highlighted. There was a significant shift away from the use of TCBZ over time, with it being replaced largely by closantel. The timing of treatments had moved earlier in the year, perhaps in response to climate change (and an altered pattern of disease). In relation to the frequency of drug treatments, there were no major changes in the overall pattern of drug treatments between the two survey points, although on both occasions approximately one-third of flock owners gave more than 3 treatments per year to ewes. In lowland areas in 2011, flock owners were rotating drug classes more often (each year and at each treatment) than in 2005, whereas in upland areas, flock owners were rotating less often and more were not rotating at all. Between 2005 and 2011, the percentage of flock owners giving quarantine treatments to bought-in stock had halved, to a very low level (approximately 10%). Using data from a complementary TCBZ resistance survey (Hanna et al., 2015), it has been shown that the way in which data are selected and which efficacy formula is applied can influence the calculation of drug efficiency and impact on diagnosis of resistance. PMID:26801598

  16. Investigation on the epidemiological factors of Clonorchis sinensis infection in an area of south China.

    PubMed

    Lin, Rui; Li, Xueming; Lan, Chungeng; Yu, Senhai; Kawanaka, Masanori

    2005-09-01

    To detect the epidemiological factors of Clonorchis sinensis infection in Hengxian County, one of counties in Guangxi Zhuang Autonomous Region where Schistosoma japonicum was endemic but eliminated in the late 1980s, a questionnaire was designed with 37 questions covering socioeconomic conditions and human behavior, contamination of the environment and fish ponds, inadequate farming/fishery practices; and the formalin-ether sedimentation technique was used to examine the feces of cats, dogs and pigs for the eggs of C. sinensis. Fresh fish was sliced and digested to detect the metacercariae of C. sinensis under a stereomicroscope. Of 1,521 people interviewed, 64% of the interviewees did not know about fluke disease or its transmission route, 46% of those who knew about the fluke believed that the infection caused no harm or only slight harm to their health. More than half of the interviewees (51%) ate raw fish at least 1-2 times per month, more among the middle-aged males. Eight percent of them used the same utensils for both raw fish and cooked food. When advice was given not to eat raw fish, 73% of the interviewees thought it was not feasible. In relation to pisciculture, 25% and 9% of the owners of fish ponds fed their fish with feces of domestic animals and human feces, respectively. The prevalences of C. sinensis infection in cats, dogs and pigs were 70, 50 and 27%, respectively, and the infection rate in fish was 40%. These results indicate the poor knowledge, and beliefs, and unhealthy behaviors in the human population. They also show poor environmental hygiene and inappropriate farming/fishery practices are important in the increase of C. sinensis prevalence in humans. Combined interventions, including health education, environmental modification, reform of traditional farming/fishery practices, mass screening and chemotherapy for humans, and the management of domestic animals are needed in developing control strategies to decrease C. sinensis infection in the human population. PMID:16438134

  17. Immune responses in rats and sheep induced by a DNA vaccine containing the phosphoglycerate kinase gene of Fasciola hepatica and liver fluke infection.

    PubMed

    Wesołowska, Agnieszka; Zawistowska-Deniziak, Anna; Norbury, Luke J; Wilkowski, Przemysław; Januszkiewicz, Kamil; Pyziel, Anna M; Zygner, Wojciech; Wędrychowicz, Halina

    2016-06-01

    Immune responses of rats and sheep following vaccination with cDNA encoding phosphoglycerate kinase of Fasciola hepatica (cDNA-FhPGK/pCMV) and F. hepatica infection were investigated in the present study. cDNA-FhPGK/pCMV vaccinated female Sprague-Dawley rats were better protected by vaccination than their male counterparts - 48% reduction in fluke burden for females and no protection for males when compared with appropriate infection control groups. Moreover, male rats developed marked leukocytosis during the study with higher neutrophil, eosinophil and monocyte responses than females. Additionally, dynamics of eosinophil and monocyte responses varied between sexes. Increased titres of anti-FhPGK IgG1 and IgG2a correlated with the protective effect of vaccination that was observed among female rats. In the case of male sheep, no differences in worm burdens and in the course of the immune response were observed following vaccination. Titres of specific antibodies detected were low, and cellular responses were not significant. Apparently, sheep immune responses induced by cDNA-FhPGK/pCMV vaccination are not effective at controlling F. hepatica infection. Poor immunogenicity of DNA vaccines in large animals is still a major obstacle of this technology that has to be overcome. PMID:27078643

  18. Epidemiological study on Clonorchis sinensis infection in Shenzhen area of Zhujiang delta in China.

    PubMed

    Zhang, Renli; Gao, Shitong; Geng, Yijie; Huang, Dana; Yu, Lei; Zhang, Shunxiang; Cheng, Jingquan; Fu, Yucai

    2007-06-01

    To study the transmission route and epidemiological features of Clonorchis sinensis infection in Shenzhen area, which is the biggest immigration city in the south of China, we examined 1,473 individuals (710 males and 763 females) to assess the current status of C. sinensis infection among the people in a village of Shenzhen in Zhujiang delta of Guangdong province, China. Freshwater snails, 630, of different species known as the first intermediate host of C. sinensis were collected and examined for cercaria infection, and 430 freshwater fishes of different species as the second intermediate host were examined for metacercaria infection. Among 1,473 people examined, 70 (4.75%) were found infected with C. sinensis. By counting eggs per gram feces (EPG), it was found that the intensity of infection in males was stronger than that of females, and the average EPG was 41.87 in all population. Snails, 1.15%, were infected with cercariae of C. sinensis. The average infection rate of freshwater fishes of 15 species with metacercariae of C. sinensis was 16.97%, and the carps reached the highest infection rate (40.74%). A questionnaire was designed with 12 questions covering socioeconomic conditions and human behavior, contamination of the environment, and fishponds. Of 1,473 interviewees, 54% did not know about fluke disease or its transmission route, 12% of those who knew about the fluke believed that the infection causes no harm or only slight harm to their health. Of the interviewees, 27%, ate raw fish at least one to two times per month. Of families, 5% used the same utensils for both raw fish and cooked food. Of the fishpond owners, 40% fed their fishes with feces of domestic animals and humans. All these factors of unhealthy behaviors, poor knowledge, inappropriate farming/fishery practices, and eating raw fish have made the prevalence of clonorchiasis increase in humans in the Shenzhen area. It is urgent to perform a control program, including health education, environmental modification, reform of traditional farming/fishery practice, mass screening, and chemotherapy for humans, and the management of domestic animals to decrease C. sinensis infection in the human population in Shenzhen. PMID:17216484

  19. Structural analysis of secretory phospholipase A2 from Clonorchis sinensis: therapeutic implications for hepatic fibrosis.

    PubMed

    Hariprasad, Gururao; Kaur, Punit; Srinivasan, Alagiri; Singh, Tej Pal; Kumar, Manoj

    2012-07-01

    Hepatic fibrosis is a common complication of the infection by the parasite, Clonorchis sinensis. There is a high incidence of this disease in the Asian countries with an increased risk of conversion to cancer. A secretory phospholipase A(2) (PLA(2)) enzyme from the parasite is implicated in the pathology. This is an attractive drug target in the light of extensive structural characterization of this class of enzyme. In this study, the structure of the enzyme was modeled based on its sequence homology to the group III bee venom PLA(2). On analysis, the overall structure essentially is comprised of three helices, two sets of β-wings and an elongated C-terminal extension. The structure is stabilized by four disulfide bonds. The structure is comprised of a calcium binding loop, active site and a substrate binding hydrophobic channel. The active site of the enzyme shows the classical features of PLA(2) with the participation of the three residues: histidine-aspartic acid-tyrosine in hydrogen bond formation. This is an interesting variation from the house keeping group III PLA(2) enzyme of human which has a histidine-aspartic acid and phenylalanine arrangement at the active site. This difference is therefore an important structural parameter that can be exploited to design specific inhibitor molecules against the pathogen PLA(2). Likewise, there are certain unique structural features in the hydrophobic channel and the putative membrane binding surface of the PLA(2) from Clonorchis sinensis that not only help understand the mechanism of action but also provide knowledge for a targeted therapy of liver fibrosis caused by the parasite. PMID:22215060

  20. Clonorchis sinensis ova in bile juice cytology from a patient with severe hyperbilirubinemia and portal vein thrombosis.

    PubMed

    Fujiya, Keiichi; Ganno, Hideaki; Ando, Masayuki; Chong, Ja-Mun

    2016-03-01

    Infection with the trematode Clonorchis sinensis is the most common human fluke infection in East Asian populations. Although this infection is associated with obstructive jaundice or choledocholithiasis, portal vein thrombosis has not been reported. Here, we report the first case of a 60-year-old man who had both C. sinensis infection and portal vein thrombosis with severe hyperbilirubinemia (75.4 mg/dl). He initially presented with abdominal pain and jaundice. Computed tomography revealed gallstones, common bile duct calculus, and thrombus in the left main branch of the portal vein. A nasobiliary tube was inserted under endoscopic retrograde cholangiography. Cytology of the bile juice revealed many C. sinensis eggs. The abdominal pain and jaundice improved following choledocholithotomy and combination treatment with a chemotherapeutic agent and anti-coagulant. This case suggests that inflammation around the portal vein as a result of C. sinensis infection has the potential to evoke portal vein thrombosis. Such cases should be treated with both a chemotherapeutic agent and anti-coagulant therapy. In conclusion, the possibility of infection with C. sinensis should be considered in patients presenting with hyperbilirubinemia and portal vein thrombosis, particularly in East Asian populations. Diagn. Cytopathol. 2016;44:223-225. © 2015 Wiley Periodicals, Inc. PMID:26663478

  1. [Progress on the Relationship between Clonorchis sinensis Infection and Cholangiocarcinoma].

    PubMed

    2015-04-01

    Currently, 12.49 million people are infected with Clonorchis sinensis in China. The incidence of bile duct carcinoma increased for recent years. More than a century ago, some scholars have put forward the idea about the relations between C. sinensis infection and cholangiocarcinoma, and committed to research the mechanism. However, the intrinsic mechanisms involved in these processes remain obscure. It is therefore important to pay more attention to the further investigation of the relevance between C. sinensis infection and bile duct carcinoma. This review summarizes the possible mechanism of cholangiocarcinoma caused by C. sinensis, which is displayed on mechanical damage, stimulation of the worms and their excretory-secretory products (ESP), abnormity of immunoreaction and molecular genetic lesions. PMID:26245128

  2. A major cathepsin B protease from the liver fluke Fasciola hepatica has atypical active site features and a potential role in the digestive tract of newly excysted juvenile parasites.

    PubMed

    Beckham, Simone A; Piedrafita, David; Phillips, Carolyn I; Samarawickrema, Nirma; Law, Ruby H P; Smooker, Peter M; Quinsey, Noelene S; Irving, James A; Greenwood, Deanne; Verhelst, Steven H L; Bogyo, Matthew; Turk, Boris; Coetzer, Theresa H; Wijeyewickrema, Lakshmi C; Spithill, Terry W; Pike, Robert N

    2009-07-01

    The newly excysted juvenile (NEJ) stage of the Fasciola hepatica lifecycle occurs just prior to invasion into the wall of the gut of the host, rendering it an important target for drug development. The cathepsin B enzymes from NEJ flukes have recently been demonstrated to be crucial to invasion and migration by the parasite. Here we characterize one of the cathepsin B enzymes (recombinant FhcatB1) from NEJ flukes. FhcatB1 has biochemical properties distinct from mammalian cathepsin B enzymes, with an atypical preference for Ile over Leu or Arg residues at the P(2) substrate position and an inability to act as an exopeptidase. FhcatB1 was active across a broad pH range (optimal activity at pH 5.5-7.0) and resistant to inhibition by cystatin family inhibitors from sheep and humans, suggesting that this enzyme would be able to function in extracellular environments in its mammalian hosts. It appears, however, that the FhcatB1 protease functions largely as a digestive enzyme in the gut of the parasite, due to the localization of a specific, fluorescently labeled inhibitor with an Ile at the P(2) position. Molecular modelling and dynamics were used to predict the basis for the unusual substrate specificity: a P(2) Ile residue positions the substrate optimally for interaction with catalytic residues of the enzyme, and the enzyme lacks an occluding loop His residue crucial for exopeptidase activity. The unique features of the enzyme, particularly with regard to its specificity and likely importance to a vital stage of the parasite's life cycle, make it an excellent target for therapeutic inhibitors or vaccination. PMID:19401154

  3. Molecular Cloning and Characterization of a Paramyosin from Clonorchis sinensis

    PubMed Central

    Park, Tae-Joon; Kang, Jung-Mi; Na, Byoung-Kuk

    2009-01-01

    Paramyosin is a myofibrillar protein present in helminth parasites and plays multifunctional roles in host-parasite interactions. In this study, we identified the gene encoding paramyosin of Clonorchis sinensis (CsPmy) and characterized biochemical and immunological properties of its recombinant protein. CsPmy showed a high level of sequence identity with paramyosin from other helminth parasites. Recombinant CsPmy (rCsPmy) expressed in bacteria had an approximate molecular weight of 100 kDa and bound both human collagen and complement 9. The protein was constitutively expressed in various developmental stages of the parasite. Imunofluorescence analysis revealed that CsPmy was mainly localized in the tegument, subtegumental muscles, and the muscle layer surrounding the intestine of the parasite. The rCsPmy showed high levels of positive reactions (74.6%, 56/75) against sera from patients with clonorchiasis. Immunization of experimental rats with rCsPmy evoked high levels of IgG production. These results collectively suggest that CsPmy is a multifunctional protein that not only contributes to the muscle layer structure but also to non-muscular functions in host-parasite interactions. Successful induction of host IgG production also suggests that CsPmy can be applied as a diagnostic antigen and/or vaccine candidate for clonorchiasis. PMID:19967083

  4. Stage-specific expression, immunolocalization of Clonorchis sinensis lysophospholipase and its potential role in hepatic fibrosis.

    PubMed

    Zhang, Fan; Liang, Pei; Chen, Wenjun; Wang, Xiaoyun; Hu, Yue; Liang, Chi; Sun, Jiufeng; Huang, Yan; Li, Ran; Li, Xuerong; Xu, Jin; Yu, Xinbing

    2013-02-01

    Lysophospholipase, belonging to the complex family of phospholipases, is supposed to play a vital role in virulence and pathogenesis of parasites and fungi. In the current study, the potential role of Clonorchis sinensis lysophospholipase (CslysoPLA) in hepatic fibrosis induced by C. sinensis was explored for the first time. In the liver of the cat infected with C. sinensis, CslysoPLA was recognized in the lumen between adult worms and surrounding bile duct epithelia together with some inside the cells by means of immunolocalization. Both Cell Counting Kit-8 (CCK-8 assay) and cell cycle analysis of human hepatic stellate cell line LX-2 showed that a higher percentage of cells were at proliferation phase after incubation with lower concentrations of recombinant CslysoPLA (rCslysoPLA). Quantitative real-time polymerase chain reaction (RT-PCR) demonstrated an upregulation in fibrogenic genes of smooth muscle α-actin, collagen III, matrix metalloproteinase 2 and tissue inhibitors of metalloproteinase II in LX-2 treated with rCslysoPLA. Moreover, human biliary epithelial cell line 5100 proliferated significantly in response to rCslysoPLA. Notably, CslysoPLA was localized in the adenomatoid hyperplastic tissue within the intrahepatic bile duct of experimentally infected rats by immunolocalization analysis. In addition, quantitative RT-PCR implied that CslysoPLA was differentially expressed at the developmental stages of C. sinensis (metacercariae, adult worms and eggs), with the highest level at metacercariae stage. Immunolocalization analysis showed that CslysoPLA was distributed in the intestine, vitelline gland, tegument and eggs in the adult worms and in the tegument and vitelline gland in the metacercariae, respectively. Collectively, it suggests that CslysoPLA might be involved in the initiation and promotion of C. sinensis-related human hepatic fibrosis and advance future studies on its promotion to C. sinensis-induced cholangiocarcinogenesis. PMID:23183703

  5. Comparative morphology of minute intestinal fluke eggs that can occur in human stools in the republic of Korea.

    PubMed

    Lee, Jin-Joo; Jung, Bong-Kwang; Lim, Hyemi; Lee, Mi Youn; Choi, Sung-Yil; Shin, Eun-Hee; Chai, Jong-Yil

    2012-09-01

    The egg morphology of minute intestinal flukes (MIF) that can occur as human infections in the Republic of Korea, i.e., Metagonimus yokogawai, M. miyatai, M. takahashii, Heterophyes nocens, Heterophyopsis continua, Stellantchasmus falcatus, Stictodora fuscata, Pygidiopsis summa, and Gymnophalloides seoi, was studied in comparison with Clonorchis sinensis. The adult worms were obtained from residents of endemic areas, and their intrauterine eggs were studied and measured using light microscopy; the length, width, length-width ratio (LWR), and Faust-Meleney index (FMI). Several specimens were processed for scanning electron microscopy (SEM), and before gold-coating, the uterine portion of each fluke was etched with a sharp pin in order to expose the eggs. The MIF eggs were ovoid, pyriform, or elliptical with a size range of 21-35×12-21 µm. S. fuscata eggs revealed the highest FMI (largest in the area) and lowest LWR, whereas P. summa eggs showed the lowest FMI and medium LWR. SEM revealed that G. seoi and S. fuscata had remarkably clean shell surface lacking the muskmelon-like structure which is prominent in C. sinensis eggs. In Metagonimus spp., H. continua, H. nocens, and S. falcatus eggs, minute surface ridges were recognizable though less prominent compared with C. sinensis. On the surface of P. summa eggs, thread-like curly structures were characteristically seen. The results revealed that important differential keys for MIF eggs include the length, width, area (FMI), shape of the eggs, and the extent of the muskmelon-like structure or ridges on their shell surface and operculum. PMID:22949747

  6. [Dolphin's flukes: A mathematical model of rigid wing].

    PubMed

    Romanenko, E V; Pushkov, S G; Lopatin, V N

    2015-01-01

    New analytical method is used to estimate hydrodynamic forces produced by dolphin's flukes. A mathematical model is proposed that describes dolphin's flukes as a flat rigid rectangular wing whose pitch axis location varies, heaving and pitching amplitudes are sufficiently large, and the phase angle shift for the combined oscillations can change arbitrarily. The dolphin's flukes kinematic parameters are obtained and used to estimate hydrodynamic forces. PMID:26852573

  7. Proteomic analysis of differentially expressed proteins in human cholangiocarcinoma cells treated with Clonorchis sinensis excretory-secretory products.

    PubMed

    Pak, Jhang Ho; Moon, Ju Hyun; Hwang, Seung-Jun; Cho, Shin-Hyeong; Seo, Sang-Beom; Kim, Tong-Soo

    2009-12-15

    Severe Clonorchis sinensis infection is a significant risk factor for malignant changes in bile ducts and surrounding liver tissues occurring as a result of direct contact with C. sinensis worms and their excretory-secretory products (ESP). However, the intrinsic molecular mechanisms involved in these processes remain obscure. To determine the effects of C. sinensis infection on protein expression in host bile duct epithelium, we examined proteomic profile changes in the human cholangiocarcinoma cell line (HuCCT1) treated with ESP at 24 h. Using a combination of 2-DE, quantitative image and MALDI-TOF MS analysis, we identified 83 proteins that were translationally modulated in response to ESP, among which 49 were up-regulated and 34 down-regulated. These proteins were classified under various biological categories, including metabolism, cell structure and architecture, proteolysis, protein modification, transport, signal transduction, and reactive oxygen species (ROS) detoxification. In particular, ESP induced the expression of redox-regulating proteins, including peroxiredoxins (Prdx 2, 3, and 6) and thioredoxin 1 (Trx 1), possibly via intracellular ROS generation. Application of the proteomic approach to identify ESP response proteins should be a prerequisite before further investigation to clarify the molecular pathways and mechanisms involved in C. sinensis infection of host cells. PMID:19798681

  8. Foodborne Intestinal Flukes in Southeast Asia

    PubMed Central

    Shin, Eun-Hee; Lee, Soon-Hyung; Rim, Han-Jong

    2009-01-01

    In Southeast Asia, a total of 59 species of foodborne intestinal flukes have been known to occur in humans. The largest group is the family Heterophyidae, which constitutes 22 species belonging to 9 genera (Centrocestus, Haplorchis, Heterophyes, Heterophyopsis, Metagonimus, Procerovum, Pygidiopsis, Stellantchasmus, and Stictodora). The next is the family Echinostomatidae, which includes 20 species in 8 genera (Artyfechinostomum, Acanthoparyphium, Echinochasmus, Echinoparyphium, Echinostoma, Episthmium, Euparyphium, and Hypoderaeum). The family Plagiorchiidae follows the next containing 5 species in 1 genus (Plagiorchis). The family Lecithodendriidae includes 3 species in 2 genera (Phaneropsolus and Prosthodendrium). In 9 other families, 1 species in 1 genus each is involved; Cathaemaciidae (Cathaemacia), Fasciolidae (Fasciolopsis), Gastrodiscidae (Gastrodiscoides), Gymnophallidae (Gymnophalloides), Microphallidae (Spelotrema), Neodiplostomidae (Neodiplostomum), Paramphistomatidae (Fischoederius), Psilostomidae (Psilorchis), and Strigeidae (Cotylurus). Various types of foods are sources of human infections. They include freshwater fish, brackish water fish, fresh water snails, brackish water snails (including the oyster), amphibians, terrestrial snakes, aquatic insects, and aquatic plants. The reservoir hosts include various species of mammals or birds.The host-parasite relationships have been studied in Metagonimus yokogawai, Echinostoma hortense, Fasciolopsis buski, Neodiplostomum seoulense, and Gymnophalloides seoi; however, the pathogenicity of each parasite species and host mucosal defense mechanisms are yet poorly understood. Clinical aspects of each parasite infection need more clarification. Differential diagnosis by fecal examination is difficult because of morphological similarity of eggs. Praziquantel is effective for most intestinal fluke infections. Continued efforts to understand epidemiological significance of intestinal fluke infections, with detection of further human cases, are required. PMID:19885337

  9. Identification and characterization of microRNAs in Clonorchis sinensis of human health significance

    PubMed Central

    2010-01-01

    Background Clonorchis sinensis is a zoonotic parasite causing clonorchiasis-associated human disease such as biliary calculi, cholecystitis, liver cirrhosis, and it is currently classified as carcinogenic to humans for cholangiocarcinoma. MicroRNAs (miRNAs) are non-coding, regulating small RNA molecules which are essential for the complex life cycles of parasites and are involved in parasitic infections. To identify and characterize miRNAs expressed in adult C. sinensis residing chronically in the biliary tract, we developed an integrative approach combining deep sequencing and bioinformatic predictions with stem-loop real-time PCR analysis. Results Here we report the use of this approach to identify and clone 6 new and 62,512 conserved C. sinensis miRNAs which belonged to 284 families. There was strong bias on families, family members and sequence nucleotides in C. sinensis. Uracil was the dominant nucleotide, particularly at positions 1, 14 and 22, which were located approximately at the beginning, middle and end of conserved miRNAs. There was no significant "seed region" at the first and ninth positions which were commonly found in human, animals and plants. Categorization of conserved miRNAs indicated that miRNAs of C. sinensis were still innovated and concentrated along three branches of the phylogenetic tree leading to bilaterians, insects and coelomates. There were two miRNA strategies in C. sinensis for its parasitic life: keeping a large category of miRNA families of different animals and keeping stringent conserved seed regions with high active innovation in other places of miRNAs mainly in the middle and the end, which were perfect for the parasite to perform its complex life style and for host changes. Conclusions The present study represented the first large scale characterization of C. sinensis miRNAs, which have implications for understanding the complex biology of this zoonotic parasite, as well as miRNA studies of other related species such as Opisthorchis viverrini and Opisthorchis felineus of human and animal health significance. PMID:20920166

  10. Tracing of the Bile-Chemotactic Migration of Juvenile Clonorchis sinensis in Rabbits by PET-CT

    PubMed Central

    Kim, Tae Im; Yoo, Won Gi; Kwak, Byung Kook; Seok, Ju–Won; Hong, Sung–Jong

    2011-01-01

    Background Adult Clonorchis sinensis live in the bile duct and cause clonorchiasis. It is known that the C. sinensis metacercariae excyst in the duodenum and migrate up to the bile duct through the common bile duct. However, no direct evidence is available on the in vivo migration of newly excysted C. sinensis juveniles (CsNEJs). Advanced imaging technologies now allow the in vivo migration and localization to be visualized. In the present study, we sought to determine how sensitively CsNEJs respond to bile and how fast they migrate to the intrahepatic bile duct using PET-CT. Methodology/Principal Findings CsNEJs were radiolabeled with 18F-fluorodeoxyglucose (18F-FDG). Rabbits with a gallbladder contraction response to cholecystokinin-8 (CCK-8) injection were pre-screened using cholescintigraphy. In these rabbits, gallbladders contracted by 50% in volume at an average of 11.5 min post-injection. The four rabbits examined were kept anesthetized and a catheter inserted into the mid duodenum. Gallbladder contraction was stimulated by injecting CCK-8 (20 ng/kg every minute) over the experiment. Anatomical images were acquired by CT initially and dynamic PET was then carried out for 90 min with a 3-min acquisition per frame. Twelve minutes after CCK-8 injection, about 3,000 18F-FDG-labeled CsNEJs were inoculated into the mid duodenum through the catheter. Photon signals were detected in the liver 7–9 min after CsNEJs inoculation, and these then increased in the whole liver with stronger intensity in the central area, presenting that the CsNEJs were arriving at the intrahepatic bile ducts. Conclusion In the duodenum, CsNEJs immediately sense bile and migrate quickly with bile-chemotaxis to reach the intrahepatic bile ducts by way of the ampulla of Vater. PMID:22180795

  11. Molecular phylogenetic identification of Fasciola flukes in Nepal.

    PubMed

    Shoriki, Takuya; Ichikawa-Seki, Madoka; Devkota, Bhuminand; Rana, Hari B; Devkota, Shiva P; Humagain, Sudeep K; Itagaki, Tadashi

    2014-12-01

    Eighty-one Fasciola flukes collected from 8 districts in Nepal were analyzed for their species identification on the basis of their spermatogenic status and nuclear ribosomal internal transcribed spacer 1 (ITS1) and for their phylogenetic relation with Fasciola flukes from other Asian countries on the basis of the mitochondrial NADH dehydrogenase subunit 1 (nad1) gene. Sixty-one flukes (75.3%) were aspermic Fasciola sp., and 20 flukes (24.7%) were identified as Fasciola gigantica. All of the aspermic flukes displayed the Fh/Fg type in ITS1, which was predominant in aspermic Fasciola sp. from China, and most (60 flukes) displayed the Fsp-ND1-N1 haplotype in the nad1, which had an identical nucleotide sequence to the major haplotype (Fg-C2) of the aspermic flukes from China. These results suggest that aspermic Fasciola sp. was introduced into Nepal from China. Furthermore, the results of the diversity indices, neutrality indices, and median-joining network analysis with reference haplotypes from Asian countries suggest that aspermic Fasciola sp. rapidly expanded its distribution. In contrasts, F. gigantica displayed 10 nad1 haplotypes, which showed higher population diversity indices than the haplotypes of aspermic flukes, indicating that the F. gigantica population was clearly distributed in Nepal earlier than the aspermic Fasciola population. Although the F. gigantica haplotypes from Nepal formed a star-like phylogeny consisting of a main founder haplotype (Fg-ND1-N1), together with some F. gigantica haplotypes from Myanmar and Thailand, the Nepal population differed genetically from F. gigantica populations of neighboring countries as each country had distinct founder haplotype(s). PMID:25025757

  12. Exome sequencing of liver fluke-associated cholangiocarcinoma.

    PubMed

    Ong, Choon Kiat; Subimerb, Chutima; Pairojkul, Chawalit; Wongkham, Sopit; Cutcutache, Ioana; Yu, Willie; McPherson, John R; Allen, George E; Ng, Cedric Chuan Young; Wong, Bernice Huimin; Myint, Swe Swe; Rajasegaran, Vikneswari; Heng, Hong Lee; Gan, Anna; Zang, Zhi Jiang; Wu, Yingting; Wu, Jeanie; Lee, Ming Hui; Huang, DaChuan; Ong, Pauline; Chan-on, Waraporn; Cao, Yun; Qian, Chao-Nan; Lim, Kiat Hon; Ooi, Aikseng; Dykema, Karl; Furge, Kyle; Kukongviriyapan, Veerapol; Sripa, Banchob; Wongkham, Chaisiri; Yongvanit, Puangrat; Futreal, P Andrew; Bhudhisawasdi, Vajarabhongsa; Rozen, Steve; Tan, Patrick; Teh, Bin Tean

    2012-06-01

    Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA. PMID:22561520

  13. Human consumption of rumen flukes of cattle in India.

    PubMed

    Sarmah, P C; Laha, R; Bhattacharjee, K; Goswami, A; Raquib, M; Kakati, P

    2014-01-01

    The practice of eating rumen flukes of cattle by a section of people living in Meghalaya, a north eastern State of India, is reported in this communication. Economically backward, some rural people belonging to Khasi, Jaintia, Garo, and Karbi tribes of Christian and Nepali communities who eat beef are accustomed to consuming cooked flukes during breakfast, meals, and also along with rice beer or alcohol. Inspection of the rumens of cattle during slaughter indicated a prevalence of flukes belonging to Cotylophoron, Paramphistomum, Calicophoron, Gastrothylax, and Fischoederius genera in 74% cases, and their collection from rumen ranged approximately from 50 g to 600 g. Biochemical analysis of flukes found 12.60% total protein, 0.78% fat, and 0.87% ash on fresh weight basis. High prevalence of flukes, easy visualization in rumen, their bulk collection, presence of nutritive value, absence of any ill effect, and lack of imminent danger of transmissibility are believed to be the rationales influencing their consumption by people. It is suggested that dietary benefits obtained from flukes might contribute to the energy transfer and inclusion in the food web. PMID:24964650

  14. Clonorchis sinensis Infestation Promotes Three-Dimensional Aggregation and Invasion of Cholangiocarcinoma Cells

    PubMed Central

    Won, Jihee; Ju, Jung-Won; Kim, Sun Min; Shin, Yoojin; Chung, Seok; Pak, Jhang Ho

    2014-01-01

    Numerous experimental and epidemiological studies have demonstrated a correlation between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA). However, the role of C. sinensis in the increased invasiveness and proliferation involved in the malignancy of CCA has not been addressed yet. Here, we investigated the possibility that C. sinensis infestation promotes expression of focal and cell-cell adhesion proteins in CCA cells and secretion of matrix metalloproteinases (MMPs). Adhesion proteins help maintain cell aggregates, and MMPs promote the three-dimensional invasion of cells into the neighboring extracellular matrix (ECM). Using a novel microfluidic assay, we quantitatively addressed the role of excretory-secretory products (ESPs) gradients from C. sinensis in promoting the invasion of cells into the neighboring ECM. PMID:25340585

  15. Immunogenicity of recombinant Bacillus subtilis spores expressing Clonorchis sinensis tegumental protein.

    PubMed

    Zhou, Zhenwen; Xia, Huimin; Hu, Xuchu; Huang, Yan; Ma, Changling; Chen, Xiaoxiang; Hu, Fengyu; Xu, Jin; Lu, Fangli; Wu, Zhongdao; Yu, Xinbing

    2008-01-01

    Clonorchis sinensis, which causes clonorchiasis, is of major socioeconomic importance in China. In this study, we report the use of CotC, a major component of the Bacillus subtilis spore coat, as a fusion partner for the expression of C. sinensis TP20.8 (Tegumental Protein 20.8 kDa) on the spore coat. Western blotting was used to identify TP20.8 surface expression on spores. Recombinant spores displaying the TP20.8 antigen were used for oral immunization and were shown to generate mucosal response in rats. TP20.8-specific secretory IgA in feces reached significant levels 2 weeks after oral dosing. This report shows that surface display of recombinant C. sinensis TP20.8 on B. subtilis spores was immunogenic and B. subtilis spores can be used as a mucosal immunization vehicle for parasite prevention and control. PMID:17924143

  16. Toxic effects of aflatoxin B1 in male Holstein calves with prior infection by flukes (Fasciola hepatica).

    PubMed

    Osuna, O; Edds, G T; Blankespoor, H D

    1977-03-01

    This experiment was designed to compare 3 dose levels of aflatoxin B1 (0.0, 0.5, and 1.0 mg/kg of body weight) and 2 infection levels of Fasciola hepatica metacercariae (0 and 220) to determine whether an additive effect from aflatoxin B1 occurs when fascioliasis is present in dairy calves. Twenty-four male, Holstein calves, 4 weeks old, and averaging 45.8 kg each, were assigned at random to 6 treatment groups, 4 calves per group: group 1--negative control; group 2--0.5 mg of aflatoxin B1/kg; group 3--1.0 mg of aflatoxin B1/kg group 4--220 metacercariae; group 5--220 metacercariae plus 0.5 mg of aflatoxin B1/kg; and group 6-220 metacercariae plus 1.0 mg of aflatoxin B1/kg. The single oral dose of 220 metacercariae was given (groups 4, 5, and 6) at the start of the 10-week experiment, and 5 weeks later, the single oral dose of aflatoxin B1 was given (groups 2, 3, 5, 6). Results from the principals, as compared with that from the controls (group 1), included significant decreases of dry matter intake (P less than 0.006), body weight (P less than 0.024), and serum albumin (P less than 0.04), and in groups 4, 5, and 6 infected with 220 flukes, there were significantly increased values of prothrombin time (P less than 0.014), serum alkaline phosphatase (P less than 0.04), and serum sorbitol dehydrogenase (P less than 0.007). Significant differences in number of flukes recovered from liver were seen in groups 4 to 6 given 0, 0.5, and 1.0 mg of aflatoxin B1/kg (P less than 0.046). The single oral dose of 22* fluke metacercariae in groups 4, 5, and 6 resulted in significantly increased concentrations of serum total protein (P less than 0.003) and globulins (P less than 0.01). Results from the development of the flukes from metacercariae to the mature state with sizes, numbers, feeding habits, and pathologic lesions were described. Differences in numbers of flukes recovered from liver of groups 4 to 6 and the presence of pneumonia in calves of group 6 indicated aflatoxin B1 produced persisting, lowered resistance. In all animals necropsied, the liver was the organ most affected by aflatoxin B1 as well as with flukes. Periportal fibrosis, monocytic infiltration, fatty infiltration, and bile duct proliferation were the usual lesions induced by aflatoxin B1. Additive toxic effects were observed in the groups 5 and 6 dosed with flukes and aflatoxin B1, with significant variations of serum and plasma values, as well as increased severity of histopathologic changes. PMID:851269

  17. Fluke abundance versus host age for an invasive trematode (Dicrocoelium dendriticum) of sympatric elk and beef cattle in southeastern Alberta, Canada

    PubMed Central

    Beck, Melissa A.; Goater, Cameron P.; Colwell, Douglas D.; van Paridon, Bradley J.

    2014-01-01

    Epidemiological parameters such as transmission rate, rate of parasite-induced host mortality, and rate of development of host defenses can be assessed indirectly by characterizing the manner in which parasite burdens change with host age. For parasites that are host generalists, estimates of these important parameters may be host-species dependent. In a cross-sectional study, we determined age–abundance profiles of infection in samples of sympatric free-ranging elk and domestic cattle infected with the lancet liver fluke, Dicrocoelium dendriticum. This parasite was introduced into Cypress Hills Provincial Park in southeastern Alberta, Canada in the mid 1990s, and now occurs in 60–90% of co-grazing elk and beef cattle examined at necropsy. The livers of 173 elk were made available by hunters during the 1997–2011 hunting seasons and livers from 35 cattle were purchased from ranchers. In elk, median worm abundance peaked in 6–24 month-olds (median = 72, range = 0–1006) then significantly declined to <10 worms/host in 10–16 year olds. The decline in fluke burden with age is not consistent with an age-related decline in exposure to metacercariae in intermediate hosts and high rates of fluke-induced host mortality are unlikely. Rather, the pattern of peak fluke burdens in elk calves and juveniles, followed by a decline in older animals is consistent with the development of a protective immune response in older hosts. There was no pattern of worm accumulation or decline in sympatric cattle, although statistical power to detect a significant effect was low. These results highlight the complexity and context-dependent nature of epidemiological processes in multi-host systems. PMID:25426422

  18. Coinfection with Clonorchis sinensis modulates murine host response against Trichinella spiralis infection.

    PubMed

    Chen, Ying; Huang, Bo; Huang, Shiguang; Yu, Xinbing; Li, Yonglong; Song, Wenjian; Li, Yongxiang; Lu, Fangli

    2013-09-01

    Concomitant infections of different species of parasites are common in the field. Infection with one parasite species likely triggers host responses that may influence the subsequent infection of another species and alter disease outcomes. So far, the majority of studies have focused on single species parasite infection, and the mechanisms of protection induced by the first parasite infection against the secondary infection remain poorly defined. In this study, we assess the impact of trematode Clonorchis sinensis infection on the course of another tissue nematode Trichinella spiralis challenge. We observed that mice with preexisting C. sinensis infection had lower worm burden of intestinal T. spiralis than those infected with T. spiralis alone; mice with preexisting C. sinensis also had severe enteric histopathological changes and higher counts of intestinal Paneth cells in responses to T. spiralis challenge. The mRNA levels of interleukin (IL)-4, IL-10, IL-13, and tumor necrosis factor (TNF)-α from the small intestine and spleen of the different groups were analyzed using quantitative real-time polymerase chain reaction. Compared with that in mice infected with T. spiralis alone, the mRNA expression of IL-13 was significantly increased in the small intestine tissues and IL-4, IL-13, and TNF-α were significantly increased in the spleen tissues in the dually infected mice. Our findings suggest that a "preexisting" trematode infection of C. sinensis is a factor which contributes to reducing the establishment of T. spiralis adult worms in the small intestine. PMID:23846239

  19. A specific PCR assay for the diagnosis of Clonorchis sinensis infection in humans, cats and fishes.

    PubMed

    Huang, Si-Yang; Tang, Jian-Dong; Song, Hui-Qun; Fu, Bao-Quan; Xu, Min-Jun; Hu, Xu-Chu; Zhang, Han; Weng, Ya-Biao; Lin, Rui-Qing; Zhu, Xing-Quan

    2012-03-01

    Clonorchiasis caused by Clonorchis sinensis is a fish-borne parasitic disease which is endemic in a number of countries. Using the sequences of the internal transcribed spacers (ITS-1 and ITS-2) of nuclear ribosomal DNA (rDNA) of C. sinensis as genetic markers, a pair of C. sinensis-specific primers was designed and used to establish a specific PCR assay for the diagnosis of C. sinensis infection in humans, cats and fish. This approach allowed the specific identification of C. sinensis after optimizing amplification conditions, with no amplicons being amplified from related heterogeneous DNA samples, and sequencing of amplicons confirmed the identity of the sequences amplified. The detection limit of this assay was 1.03 pg of adult C. sinensis, 1.1 metacercariae per gram of fish filet, and a single egg in human and cat feces. The PCR assay should provide a useful tool for the diagnosis and molecular epidemiological investigation of clonorchiasis in humans and animals. PMID:21777693

  20. Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review.

    PubMed

    Machicado, Claudia; Marcos, Luis A

    2016-06-15

    Only three helminths (Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis) are directly associated with carcinogenesis in humans whereas the role of other parasites in cancer remains unclear. This study aimed to perform a systematic review to identify recent insights in the role of other parasite infections in carcinogenesis. We conducted systematic searches of MEDLINE and EMBASE on July 2015. Our primary outcome was the association between parasitic infections and carcinogenesis. Out of 1,266 studies, 19 were selected for detailed evaluation (eight for helminths and 11 for protozoa). The mechanisms of helminth-induced cancer included chronic inflammation, sustained proliferation, modulation of the host immune system, reprogramming of glucose metabolism and redox signaling, induction of genomic instability and destabilization of suppressor tumor proteins, stimulation of angiogenesis, resisting cell death, and activation of invasion and metastasis. In addition to the current knowledge, the following parasites were found in cancers or tumors: Echinococcus, Strongyloides, Fasciola, Heterakis, Platynosomum and Trichuris. Additional parasites were found in this systematic review that could potentially be associated with cancers or tumors but further evidence is needed to elaborate a cause-effect relationship. PMID:26840624

  1. Identification, immunolocalization, and characterization analyses of an exopeptidase of papain superfamily, (cathepsin C) from Clonorchis sinensis.

    PubMed

    Liang, Pei; He, Lei; Xu, Yanquan; Chen, Xueqing; Huang, Yan; Ren, Mengyu; Liang, Chi; Li, Xuerong; Xu, Jin; Lu, Gang; Yu, Xinbing

    2014-10-01

    Cathepsin C is an important exopeptidase of papain superfamily and plays a number of great important roles during the parasitic life cycle. The amino acid sequence of cathepsin C from Clonorchis sinensis (C. sinensis) showed 54, 53, and 49% identities to that of Schistosoma japonicum, Schistosoma mansoni, and Homo sapiens, respectively. Phylogenetic analysis utilizing the sequences of papain superfamily of C. sinensis demonstrated that cathepsin C and cathepsin Bs came from a common ancestry. Cathepsin C of C. sinensis (Cscathepsin C) was identified as an excretory/secretory product by Western blot analysis. The results of transcriptional level and translational level of Cscathepsin C at metacercaria stage were higher than that at adult worms. Immunolocalization analysis indicated that Cscathepsin C was specifically distributed in the suckers (oral sucker and ventral sucker), eggs, vitellarium, intestines, and testis of adult worms. In the metacercaria, it was mainly detected on the cyst wall and excretory bladder. Combining with the results mentioned above, it implies that Cscathepsin C may be an essential proteolytic enzyme for proteins digestion of hosts, nutrition assimilation, and immune invasion of C. sinensis. Furthermore, it may be a potential diagnostic antigen and drug target against C. sinensis infection. PMID:25138068

  2. Prevalence of Clonorchis sinensis Infection among Residents along 5 Major Rivers in the Republic of Korea

    PubMed Central

    Jeong, Young-Il; Shin, Hee-Eun; Lee, Sang-Eun; Cheun, Hyeng-Il; Ju, Jung-Won; Kim, Jung-Yeon; Park, Mi Yeoun; Cho, Shin-Hyeong

    2016-01-01

    Clonorchis sinensis is currently the most important parasite affecting public health problems in the Republic of Korea. We investigated the prevalence of C. sinensis infection among residents living along 5 major rivers in Korea. A total of 42,562 individual stool samples were collected from 37 localities and examined using the formalin-ether sedimentation technique. Helminth eggs were detected in 4,052 (9.5%) residents and 3,586 (8.4%) were infected with C. sinensis. The egg positive rate of C. sinensis in Nakdong, Seomjin, Geum, Yeongsan, and Han River was 11.7%, 9.9%, 6.5%, 3.1%, and 1.0%, respectively. The overall prevalence of clonorchiasis by sex was 11.2% in males and 6.2% in females. The age-prevalence was the highest in the 50-59 years band. It has been reconfirmed that the endemicity of clonorchiasis is higher in southern areas of Korea, especially along Nakdong and Seomjin Rivers. A combination of continuous control programs with health education initiatives is urgently required in these highly endemic areas of clonorchiasis in Korea. PMID:27180582

  3. Advanced Enzymology, Expression Profile and Immune Response of Clonorchis sinensis Hexokinase Show Its Application Potential for Prevention and Control of Clonorchiasis

    PubMed Central

    Tang, Zeli; Xie, Zhizhi; Lin, Zhipeng; Sun, Hengchang; Wan, Shuo; Li, Xuerong; Huang, Yan; Yu, Xinbing; Xu, Jin

    2015-01-01

    Background Approximately 35 million people are infected with Clonorchis sinensis (C. sinensis) globally, of whom 15 million are in China. Glycolytic enzymes are recognized as crucial molecules for trematode survival and have been targeted for vaccine and drug development. Hexokinase of C. sinensis (CsHK), as the first key regulatory enzyme of the glycolytic pathway, was investigated in the current study. Principal Findings There were differences in spatial structure and affinities for hexoses and phosphate donors between CsHK and HKs from humans or rats, the definitive hosts of C. sinensis. Effectors (AMP, PEP, and citrate) and a small molecular inhibitor regulated the enzymatic activity of rCsHK, and various allosteric systems were detected. CsHK was distributed in the worm extensively as well as in liver tissue and serum from C. sinensis infected rats. Furthermore, high-level specific IgG1 and IgG2a were induced in rats by immunization with rCsHK. The enzymatic activity of CsHK was suppressed by the antibody in vitro. Additionally, the survival of C. sinensis was inhibited by the antibody in vivo and in vitro. Conclusions/Significance Due to differences in putative spatial structure and enzymology between CsHK and HK from the host, its extensive distribution in adult worms, and its expression profile as a component of excretory/secretory products, together with its good immunogenicity and immunoreactivity, as a key glycolytic enzyme, CsHK shows potential as a vaccine and as a promising drug target for Clonorchiasis. PMID:25799453

  4. Fasciola hepatica: development of the tegument of normal and gamma-irradiated flukes during infection in rats and mice.

    PubMed

    Burden, D J; Bland, A P; Hughes, D L; Hammet, N C

    1983-02-01

    Rats and mice were infected with either normal metacercariae or metacercariae gamma-irradiated at 3 krad. or 4 krad. Flukes were recovered at various times after infection and their teguments examined using a transmission electron microscope. In normal flukes, the secretory granules T0, T1 and T2 were all seen during tegumental development. The teguments of flukes from mice developed faster than the corresponding teguments in rats. T0 granules were present from day 0 to day 10 post-infection (p.i.) in mouse flukes and from day 0 to day 14 p.i. in rat flukes. T1 granules first appeared in mouse flukes by day 4 p.i. but not until day 8 p.i. in rat flukes. T2 granules were seen in mouse flukes 2 days p.i. but not before 6 days p.i. in rat flukes. gamma-Irradiation at 4 krad prevented normal tegumental development in flukes from both rats and mice. T0 granules were present at all times in flukes from either host. T1 granules were produced in mouse flukes but their appearance was delayed until day 6 p.i. No significant production of T2 granules occurred in flukes from either host. Parasite survival was also affected by gamma-irradiation and none of the flukes reached maturity. Flukes from rats died between 10 and 21 days p.i. and flukes from mice died between 14 and 28 days p.i. gamma-Irradiation of metacercariae at 3 krad. had an extremely variable effect on subsequent tegumental development in both rats and mice. Some flukes developed normally, some showed development associated with gamma-irradiation at 4 krad, whilst some showed intermediate development. PMID:6835695

  5. An integrated pipeline for next generation sequencing and annotation of the complete mitochondrial genome of the giant intestinal fluke, Fasciolopsis buski (Lankester, 1857) Looss, 1899

    PubMed Central

    Biswal, Devendra Kumar; Ghatani, Sudeep; Shylla, Jollin A.; Sahu, Ranjana; Mullapudi, Nandita

    2013-01-01

    Helminths include both parasitic nematodes (roundworms) and platyhelminths (trematode and cestode flatworms) that are abundant, and are of clinical importance. The genetic characterization of parasitic flatworms using advanced molecular tools is central to the diagnosis and control of infections. Although the nuclear genome houses suitable genetic markers (e.g., in ribosomal (r) DNA) for species identification and molecular characterization, the mitochondrial (mt) genome consistently provides a rich source of novel markers for informative systematics and epidemiological studies. In the last decade, there have been some important advances in mtDNA genomics of helminths, especially lung flukes, liver flukes and intestinal flukes. Fasciolopsis buski, often called the giant intestinal fluke, is one of the largest digenean trematodes infecting humans and found primarily in Asia, in particular the Indian subcontinent. Next-generation sequencing (NGS) technologies now provide opportunities for high throughput sequencing, assembly and annotation within a short span of time. Herein, we describe a high-throughput sequencing and bioinformatics pipeline for mt genomics for F. buski that emphasizes the utility of short read NGS platforms such as Ion Torrent and Illumina in successfully sequencing and assembling the mt genome using innovative approaches for PCR primer design as well as assembly. We took advantage of our NGS whole genome sequence data (unpublished so far) for F. buski and its comparison with available data for the Fasciola hepatica mtDNA as the reference genome for design of precise and specific primers for amplification of mt genome sequences from F. buski. A long-range PCR was carried out to create an NGS library enriched in mt DNA sequences. Two different NGS platforms were employed for complete sequencing, assembly and annotation of the F. buski mt genome. The complete mt genome sequences of the intestinal fluke comprise 14,118 bp and is thus the shortest trematode mitochondrial genome sequenced to date. The noncoding control regions are separated into two parts by the tRNA-Gly gene and don’t contain either tandem repeats or secondary structures, which are typical for trematode control regions. The gene content and arrangement are identical to that of F. hepatica. The F. buski mtDNA genome has a close resemblance with F. hepatica and has a similar gene order tallying with that of other trematodes. The mtDNA for the intestinal fluke is reported herein for the first time by our group that would help investigate Fasciolidae taxonomy and systematics with the aid of mtDNA NGS data. More so, it would serve as a resource for comparative mitochondrial genomics and systematic studies of trematode parasites. PMID:24255820

  6. Prevalence of Clonorchis sinensis infection in freshwater fishes in northeastern China.

    PubMed

    Zhang, Y; Chang, Q C; Zhang, Y; Na, L; Wang, W T; Xu, W W; Gao, D Z; Liu, Z X; Wang, C R; Zhu, X Q

    2014-08-29

    The prevalence of Clonorchis sinensis infection in freshwater fishes was surveyed in Heilongjiang Province, northeastern China, between August 2011 and September 2013. Thirteen species of freshwater fish (n=3221) and one species of shrimp (n=93) were collected from Songhua river, Nenjiang river and other lakes or ponds in 37 sites of 15 representative cities in Heilongjiang Province. They were individually examined by digestion technique, and the C. sinensis metacercariae were identified morphologically followed by confirmation using sequences of the second internal transcribed spacer of ribosomal DNA. Ten of the 13 examined species of freshwater fishes were infected with C. sinensis metacercariae, while all shrimps were negative. The overall prevalence of C. sinensis infection in 3221 examined freshwater fishes was 19.96%, with 42.57% (272/639) in Pseudorasbora parva, 22.55% (83/368) in Hemicculter leuciclus, 20.44% (121/592) in Carassius auratus, 17.71% (68/384) in Saurogobio dabryi, 10.85% (23/212) in Rhodeus ocellatus, 10.54% (48/455) in Phoxinus lagowskii, 8.20% (21/256) in Perccottus glehnii, 6.25% (5/80) in Misgurnus anguillicaudatus, 4.55% (1/22) in Xenocypris davidi, and 1.49% (1/67) in Cyprinus carpio. The average infection intensity in P. parva was 103.3 encysted metacercariae per gram of fish meat in Zhaoyuan city. The average prevalence of C. sinensis infection in Songhua river, Nenjiang river and lakes or ponds were 31.96% (503/1574), 11.30% (102/903) and 7.93% (59/744), respectively. The prevalence of C. sinensis infection in Zhaoyuan city (43.68%) was the highest among all sampling locations. These results revealed a high-prevalence of C. sinensis infection in freshwater fishes in Heilongjiang Province, northeastern China, posing significant public health concern. PMID:24880648

  7. Comparison of two serpins of Clonorchis sinensis by bioinformatics, expression, and localization in metacercaria

    PubMed Central

    Yang, Yabo; Hu, Dong; Wang, Lexun; Liang, Chi; Hu, Xuchu; Xu, Jin; Huang, Yan; Yu, Xinbing

    2014-01-01

    Clonorchiasis, which has been an important public health problem in China, is caused by ingestion of raw or undercooked fish contaminated by live metacercaria. Therefore, preventing fish from infecting is of great significance for controlling the disease. SERPINs (serine protease inhibitors) are well known as negative regulators of hemostasis, thrombolysis, and innate immune responses. In the present study, two full-length sequences encoding SERPIN were identified from metacercaria cDNA library of Clonorchis sinensis (C. sinensis) and were denominated as CsSERPIN and CsSERPIN3, respectively. Bioinformatics analysis showed that the two sequences shares 35.9% identity to each other. Both of the sequences have SERPIN domain and the greatest difference between the two domains is the reactive centre loop. Transmembrane region was found in CsSERPIN3 while not in CsSERPIN. The expression of the two CsSERPINs was significantly higher at the life stage of metacercaria than that of adult. The transcription levels of CsSERPIN and CsSERPIN3 at metacercaria stage were 3.249- and 11.314-fold of that at adult stage, respectively. Furthermore, the expression of CsSERPIN was 4.32-fold of that of CsSERPIN3 at metacercaria stage. Immunobiochemistry revealed that CsERPIN was dispersed at subtegument and oral sucker of metacercaria, while CsSERPIN3 localized intensely in the tegument of metacercaria of C. sinensis inside of the cyst wall. All these indicated that the CsSERPINs play important roles at metacercaria stage of the parasite. CsSERPIN may take part in regulation of endogenous serine proteinase and CsSERPIN3 may be involved in immune evasion and be a potential candidate for vaccine and drug target for clonorchiasis. PMID:24831344

  8. Molecular Cloning and Characterization of Growth Factor Receptor Bound-Protein in Clonorchis sinensis

    PubMed Central

    Bai, Xuelian; Lee, Ji-Yun; Kim, Tae Im; Dai, Fuhong; Lee, Tae-Jin; Hong, Sung-Jong

    2014-01-01

    Background Clonorchis sinensis causes clonorchiasis, a potentially serious disease. Growth factor receptor-bound protein 2 (Grb2) is a cytosolic protein conserved among animals and plays roles in cellular functions such as meiosis, organogenesis and energy metabolism. In the present study, we report first molecular characters of growth factor receptor bound-protein (CsGrb2) from C. sinensis as counter part of Grb2 from animals and its possible functions in development and organogenesis of C. sinensis. Methodology/Principal Findings A CsGrb2 cDNA clone retrieved from the C. sinensis transcriptome encoded a polypeptide with a SH3-SH2-SH3 structure. Recombinant CsGrb2 was bacterially produced and purified to homogeneity. Native CsGrb2 with estimated molecular weight was identified from C. sinensis adult extract by western blotting using a mouse immune serum to recombinant CsGrb2. CsGrb2 transcripts was more abundant in the metacercariae than in the adults. Immunohistochemical staining showed that CsGrb2 was localized to the suckers, mesenchymal tissues, sperms in seminal receptacle and ovary in the adults, and abundantly expressed in most organs of the metacercariae. Recombinant CsGrb2 was evaluated to be little useful as a serodiagnostic reagent for C. sinesis human infections. Conclusion Grb2 protein found in C. sinensis was conserved among animals and suggested to play a role in the organogenesis, energy metabolism and mitotic spermatogenesis of C. sinensis. These findings from C. sinensis provide wider understanding on diverse function of Grb2 in lower animals such as platyhelminths. PMID:24454892

  9. Molecular cloning and functional characterization of a glucose transporter (CsGLUT) in Clonorchis sinensis.

    PubMed

    Ahn, Seong Kyu; Cho, Pyo Yun; Na, Byoung-Kuk; Hong, Sung-Jong; Nam, Ho-Woo; Sohn, Woon-Mok; Ardelli, Bernadette F; Park, Yun-Kyu; Kim, Tong-Soo; Cha, Seok Ho

    2016-01-01

    A complementary DNA (cDNA) encoding a glucose transporter of Clonorchis sinensis (CsGLUT) was isolated from the adult C. sinensis cDNA library. The open reading frame of CsGLUT cDNA consists of 1653 base pairs that encode a 550-amino acid residue protein. Hydropathy analysis suggested that CsGLUT possess 12 putative membrane-spanning domains. The Northern blot analysis result using poly(A)(+)RNA showed a strong band at ~2.1 kb for CsGLUT. When expressed in Xenopus oocytes, CsGLUT mediated the transport of radiolabeled deoxy-D-glucose in a time-dependent but sodium-independent manner. Concentration-dependency results showed saturable kinetics and followed the Michaelis-Menten equation. Nonlinear regression analyses yielded a Km value of 588.5 ± 53.0 μM and a Vmax value of 1500.0 ± 67.5 pmol/oocyte/30 min for [1,2-(3)H]2-deoxy-D-glucose. No trans-uptakes of bile acid (taurocholic acid), amino acids (tryptophan and arginine), or p-aminohippuric acid were observed. CsGLUT-mediated transport of deoxyglucose was significantly and concentration-dependently inhibited by radio-unlabeled deoxyglucose and D-glucose. 3-O-Methylglucose at 10 and 100 μM inhibited deoxyglucose uptake by ~50 % without concentration dependence. No inhibitory effects by galactose, mannose, and fructose were observed. This work may contribute to the molecular biological study of carbohydrate metabolism and new drug development of C. sinensis. PMID:26450594

  10. Comparison of two serpins of Clonorchis sinensis by bioinformatics, expression, and localization in metacercaria.

    PubMed

    Yang, Yabo; Hu, Dong; Wang, Lexun; Liang, Chi; Hu, Xuchu; Xu, Jin; Huang, Yan; Yu, Xinbing

    2014-06-01

    Clonorchiasis, which has been an important public health problem in China, is caused by ingestion of raw or undercooked fish contaminated by live metacercaria. Therefore, preventing fish from infecting is of great significance for controlling the disease. SERPINs (serine protease inhibitors) are well known as negative regulators of hemostasis, thrombolysis, and innate immune responses. In the present study, two full-length sequences encoding SERPIN were identified from metacercaria cDNA library of Clonorchis sinensis (C. sinensis) and were denominated as CsSERPIN and CsSERPIN3, respectively. Bioinformatics analysis showed that the two sequences shares 35.9% identity to each other. Both of the sequences have SERPIN domain and the greatest difference between the two domains is the reactive centre loop. Transmembrane region was found in CsSERPIN3 while not in CsSERPIN. The expression of the two CsSERPINs was significantly higher at the life stage of metacercaria than that of adult. The transcription levels of CsSERPIN and CsSERPIN3 at metacercaria stage were 3.249- and 11.314-fold of that at adult stage, respectively. Furthermore, the expression of CsSERPIN was 4.32-fold of that of CsSERPIN3 at metacercaria stage. Immunobiochemistry revealed that CsERPIN was dispersed at subtegument and oral sucker of metacercaria, while CsSERPIN3 localized intensely in the tegument of metacercaria of C. sinensis inside of the cyst wall. All these indicated that the CsSERPINs play important roles at metacercaria stage of the parasite. CsSERPIN may take part in regulation of endogenous serine proteinase and CsSERPIN3 may be involved in immune evasion and be a potential candidate for vaccine and drug target for clonorchiasis. PMID:24831344

  11. Low Divergence of Clonorchis sinensis in China Based on Multilocus Analysis

    PubMed Central

    Sun, Jiufeng; Huang, Yan; Huang, Huaiqiu; Liang, Pei; Wang, Xiaoyun; Mao, Qiang; Men, Jingtao; Chen, Wenjun; Deng, Chuanhuan; Zhou, Chenhui; Lv, Xiaoli; Zhou, Juanjuan; Zhang, Fan; Li, Ran; Tian, Yanli; Lei, Huali; Liang, Chi; Hu, Xuchu; Xu, Jin; Li, Xuerong; XinbingYu

    2013-01-01

    Clonorchis sinensis, an ancient parasite that infects a number of piscivorous mammals, attracts significant public health interest due to zoonotic exposure risks in Asia. The available studies are insufficient to reflect the prevalence, geographic distribution, and intraspecific genetic diversity of C. sinensis in endemic areas. Here, a multilocus analysis based on eight genes (ITS1, act, tub, ef-1a, cox1, cox3, nad4 and nad5 [4.986 kb]) was employed to explore the intra-species genetic construction of C. sinensis in China. Two hundred and fifty-six C. sinensis isolates were obtained from environmental reservoirs from 17 provinces of China. A total of 254 recognized Multilocus Types (MSTs) showed high diversity among these isolates using multilocus analysis. The comparison analysis of nuclear and mitochondrial phylogeny supports separate clusters in a nuclear dendrogram. Genetic differentiation analysis of three clusters (A, B, and C) showed low divergence within populations. Most isolates from clusters B and C are geographically limited to central China, while cluster A is extraordinarily genetically diverse. Further genetic analyses between different geographic distributions, water bodies and hosts support the low population divergence. The latter haplotype analyses were consistent with the phylogenetic and genetic differentiation results. A recombination network based on concatenated sequences showed a concentrated linkage recombination population in cox1, cox3, nad4 and nad5, with spatial structuring in ITS1. Coupled with the history record and archaeological evidence of C. sinensis infection in mummified desiccated feces, these data point to an ancient origin of C. sinensis in China. In conclusion, we present a likely phylogenetic structure of the C. sinensis population in mainland China, highlighting its possible tendency for biogeographic expansion. Meanwhile, ITS1 was found to be an effective marker for tracking C. sinensis infection worldwide. Thus, the present study improves our understanding of the global epidemiology and evolution of C. sinensis. PMID:23825605

  12. Fasciola hepatica: a technique for the study of gut penetration by juvenile flukes.

    PubMed

    Burden, D J; Bland, A P; Hughes, D L; Hammet, N C

    1981-10-01

    A method using light and electron microscopes is described which is suitable for the examination of gut penetration by juvenile Fasciola hepatica. It involved the ligation of small sections of the small intestine of rats and the introduction of artificially excysted flukes into these gut loops. By restricting the area of infection in this way it was possible to either recover flukes from the gut lumen or to prepare ultrathin sections for electron microscopy of flukes penetrating the gut wall. In addition, flukes were recovered from the body cavity at various times after preparation of loops in resistant and naive rats. It was found that more flukes reached the body cavity in naive rats than in resistant rats, demonstrating a resistance to infection in the gut loops of sensitized rats. PMID:7329714

  13. Gene diversity and genetic variation in lung flukes (genus Paragonimus).

    PubMed

    Blair, David; Nawa, Yukifumi; Mitreva, Makedonka; Doanh, Pham Ngoc

    2016-01-01

    Paragonimiasis caused by lung flukes (genus Paragonimus) is a neglected disease occurring in Asia, Africa and the Americas. The genus is species-rich, ancient and widespread. Genetic diversity is likely to be considerable, but investigation of this remains confined to a few populations of a few species. In recent years, studies of genetic diversity have moved from isoenzyme analysis to molecular phylogenetic analysis based on selected DNA sequences. The former offered better resolution of questions relating to allelic diversity and gene flow, whereas the latter is more suitable for questions relating to molecular taxonomy and phylogeny. A picture is emerging of a highly diverse taxon of parasites, with the greatest diversity found in eastern and southern Asia where ongoing speciation might be indicated by the presence of several species complexes. Diversity of lung flukes in Africa and the Americas is very poorly sampled. Functional molecules that might be of value for immunodiagnosis, or as targets for medical intervention, are of great interest. Characterisation of these from Paragonimus species has been ongoing for a number of years. However, the imminent release of genomic and transcriptomic data for several species of Paragonimus will dramatically increase the rate of discovery of such molecules, and illuminate their diversity within and between species. PMID:26740357

  14. Molecular characterization of Clonorchis sinensis secretory myoglobin: Delineating its role in anti-oxidative survival

    PubMed Central

    2014-01-01

    Background Clonorchiasis is a globally important, neglected food-borne disease caused by Clonorchis sinensis (C. sinensis), and it is highly related to cholangiocarcinoma and hepatocellular carcinoma. Increased molecular evidence has strongly suggested that the adult worm of C. sinensis continuously releases excretory-secretory proteins (ESPs), which play important roles in the parasite-host interactions, to establish successful infection and ensure its own survival. Myoglobin, a hemoprotein, is present in high concentrations in trematodes and ESPs. To further understand the biological function of CsMb and its putative roles in the interactions of C. sinensis with its host, we explored the molecular characterization of CsMb in this paper. Methods We expressed CsMb and its mutants in E. coli BL21 and identified its molecular characteristics using bioinformatics analysis and experimental approaches. Reverse transcription PCR analysis was used to measure myoglobin transcripts of C. sinensis with different culture conditions. The peroxidase activity of CsMb was confirmed by spectrophotometry. We co-cultured RAW264.7 cells with recombinant CsMb (rCsMb), and we then measured the production of hydrogen peroxide (H2O2) and nitric oxide (NO) in addition to the mRNA levels of inducible nitric oxide synthase (iNOS), Cu-Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) in activated RAW264.7 cells. Results In the in vitro culture of adult worms, the transcripts of CsMb increased with the increase of oxygen content. Oxidative stress conditions induced by H2O2 increased the levels of CsMb transcripts in a dose-dependent manner. Furthermore, CsMb catalyzed oxidation reactions in the presence of H2O2, and amino acid 34 of CsMb played an essential role in its reaction with H2O2. In addition, CsMb significantly reduced H2O2 and NO levels in LPS-activated macrophages, and CsMb downregulated iNOS and SOD expression in activated macrophages. Conclusion The present study is the first to investigate the peroxidase activity of CsMb. This investigation suggested that C. sinensis may decrease the redox activation of macrophages by CsMb expression to evade host immune responses. These studies contribute to a better understanding of the role of CsMb in the molecular mechanisms involved in ROS detoxification by C. sinensis. PMID:24885788

  15. Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine

    PubMed Central

    Uddin, Md. Hafiz; Choi, Min-Ho; Kim, Woo Ho; Jang, Ja-June; Hong, Sung-Tae

    2015-01-01

    Background Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA). Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model. Methods Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl.), infected with C. sinensis (Cs), ingested N-nitrosodimethylamine (NDMA), and both Cs infected and NDMA introduced (Cs+NDMA). The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR) and western blotting. Principal Findings CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA). The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model. Conclusions/Significance The present findings suggest that oncogenes, PSMD10 and CDK4, and tumor suppressors, p53 and RB, are involved in the carcinogenesis process of C. sinensis induced CCA in hamsters. PMID:26313366

  16. Gill trematodes (flukes) in wild-caught killifish (Fundulus heteroclitus).

    PubMed

    Goulding, David R; Blankenship-Paris, Terry L; Lewbart, Gregory A; Myers, Page H; Demianenko, Tracy K; Clark, James A; Forsythe, Diane B

    2004-03-01

    Three wild caught killifish (Fundulus heteroclitus) on an Institutional Animal Care and Use Committee-approved protocol were found dead within 2 days after being received. The fish were housed in two separate aquaria. Aquarium water was evaluated, and pH, salinity, ammonia, nitrate, and nitrite levels were within acceptable parameters. Several remaining fish appeared to be slow-moving and were presented for necropsy. Multiple, scattered, ulcerated skin lesions (diameter, 1 to 5 mm) were noted at necropsy and were cultured. No pathogenic bacteria were isolated. Wet-mount samples of the gills revealed multiple cysts at the gill margins, each containing a motile organism. No other gill parasites were detected. A diagnosis of trematodiasis was made. The cysts were identified as encysted metacercariae of a digenetic trematode. We surmise that the large numbers of gill flukes combined with the stress of recent shipment likely caused the observed morbidity and mortality. PMID:15053506

  17. Observations on the biology, epidemiology and economic relevance of rumen flukes (Paramphistomidae) in cattle kept in a temperate environment.

    PubMed

    Sargison, Neil; Francis, Emily; Davison, Chloe; Bronsvoort, Barend M deC; Handel, Ian; Mazeri, Stella

    2016-03-30

    There is concern about the probable recent introduction, increased prevalence and potential economic impact of rumen fluke infection of United Kingdom cattle. A study of 339 cattle slaughtered in a Scottish red meat abattoir was undertaken with the aims of describing the prevalence and geographical distribution of rumen fluke infection, estimating its effect on production, and evaluating faecal egg counts (FECs) as a tool to diagnose infection in live animals and study the epidemiology of the disease. The overall proportion of cattle consigned to the abattoir from northern United Kingdom with rumen fluke infection in the forestomachs was 0.29. Rumen flukes were distributed predominantly in the cranial sac of the rumen and adjacent to the reticular groove. Overall, a mean of 213 and median of 44 rumen flukes was identified in the forestomachs of rumen fluke-positive cattle. The mean and median FECs of animals were 26.01 and 5.20 eggs per gram (epg), respectively. There was a significant difference between the mean FECs per rumen fluke of 0.08 and 0.13epg during summer/autumn and winter sampling periods, respectively. The overall correlation between rumen fluke FECs and the number of flukes in the forestomach was high, albeit lower in the summer/autumn than in the winter period. The sensitivities of rumen fluke FECs for the identification of flukes in the forestomach during the summer/autumn and winter sampling periods were 0.65 and 0.85, respectively. These results will aid in the interpretation of rumen fluke FECs when monitoring cattle health and production and studying the parasite's epidemiology in a temperate environment, thereby informing rational, precise and sustainable disease control. PMID:26921033

  18. Host specificity of a parasitic fluke: is Posthodiplostomum minimum a centrarchid-infecting generalist or specialist?

    PubMed

    Lane, Beth; Spier, Timothy; Wiederholt, Julia; Meagher, Shawn

    2015-02-01

    Parasite host specificity has important implications for species diversity estimates, food web dynamics, and host shifts. "White grub" is the metacercaria stage of a fluke ( Posthodiplostomum minimum ) that occurs in many fish species, but no attempt has been made to quantify variation in host use by this worm. Here we used 2 approaches to evaluate host specificity within the strain that infects centrarchids ( P. minimum centrarchi). First, we measured parasite loads in 2 centrarchid hosts, bluegill ( Lepomis macrochirus ) and white crappie ( Pomoxis annularis ), from Spring Lake in McDonough County, Illinois. We found that infection levels differed significantly between these hosts. Prevalence in bluegill was 100% and the median intensity was 940 metacercariae, but only 57% of white crappie were infected (median intensity = 4). Site specificity of white grub also differed significantly between the 2 hosts. In bluegills, kidneys were most heavily infected, whereas in white crappies, livers harbored the most worms. We also performed a literature survey of P. minimum prevalence estimates from 14 centrarchid species from other localities. We calculated the mean white grub prevalence for each host species and used this to calculate STD*, a quantitative index of host specificity. STD* was 1.33, significantly closer to the value for a specialist (STD* = 1.00) than a generalist (STD* = 2.00). This reflects the fact that P. minimum prevalence is higher in Lepomis species than it is in centrarchids outside this genus. These data show that P. minimum centrarchi specializes on Lepomis species, but the causes of this specialization are unknown. This worm may be a single species that differs in host use due to ecological or physiological host differences, or it may be a complex of species that vary in host use for similar reasons. Genetic data are required to evaluate these possibilities. PMID:25260116

  19. The genome of the blood fluke Schistosoma mansoni

    PubMed Central

    Berriman, Matthew; Haas, Brian J.; LoVerde, Philip T.; Wilson, R. Alan; Dillon, Gary P.; Cerqueira, Gustavo C.; Mashiyama, Susan T.; Al-Lazikani, Bissan; Andrade, Luiza F.; Ashton, Peter D.; Aslett, Martin A.; Bartholomeu, Daniella C.; Blandin, Gaelle; Caffrey, Conor R.; Coghlan, Avril; Coulson, Richard; Day, Tim A.; Delcher, Art; DeMarco, Ricardo; Djikeng, Appoliniare; Eyre, Tina; Gamble, John A.; Ghedin, Elodie; Gu, Yong; Hertz-Fowler, Christiane; Hirai, Hirohisha; Hirai, Yuriko; Houston, Robin; Ivens, Alasdair; Johnston, David A.; Lacerda, Daniela; Macedo, Camila D.; McVeigh, Paul; Ning, Zemin; Oliveira, Guilherme; Overington, John P.; Parkhill, Julian; Pertea, Mihaela; Pierce, Raymond J.; Protasio, Anna V.; Quail, Michael A.; Rajandream, Marie-Adèle; Rogers, Jane; Sajid, Mohammed; Salzberg, Steven L.; Stanke, Mario; Tivey, Adrian R.; White, Owen; Williams, David L.; Wortman, Jennifer; Wu, Wenjie; Zamanian, Mostafa; Zerlotini, Adhemar; Fraser-Liggett, Claire M.; Barrell, Barclay G.; El-Sayed, Najib M.

    2009-01-01

    Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. We report here analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and novel families of micro-exon genes that undergo frequent alternate splicing. As the first sequenced flatworm, and a representative of the lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, while the identification of membrane receptors, ion channels and more than 300 proteases, provide new insights into the biology of the life cycle and novel targets. Bioinformatics approaches have identified metabolic chokepoints while a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease. PMID:19606141

  20. Prevalence and Sequence-Based Identity of Rumen Fluke in Cattle and Deer in New Caledonia.

    PubMed

    Cauquil, Laura; Hüe, Thomas; Hurlin, Jean-Claude; Mitchell, Gillian; Searle, Kate; Skuce, Philip; Zadoks, Ruth

    2016-01-01

    An abattoir survey was performed in the French Melanesian archipelago of New Caledonia to determine the prevalence of paramphistomes in cattle and deer and to generate material for molecular typing at species and subspecies level. Prevalence in adult cattle was high at animal level (70% of 387 adult cattle) and batch level (81%). Prevalence was lower in calves at both levels (33% of 484 calves, 51% at batch level). Animals from 2 of 7 deer farms were positive for rumen fluke, with animal-level prevalence of 41.4% (29/70) and 47.1% (33/70), respectively. Using ITS-2 sequencing, 3 species of paramphistomes were identified, i.e. Calicophoron calicophorum, Fischoederius elongatus and Orthocoelium streptocoelium. All three species were detected in cattle as well as deer, suggesting the possibility of rumen fluke transmission between the two host species. Based on heterogeneity in ITS-2 sequences, the C. calicophorum population comprises two clades, both of which occur in cattle as well as deer. The results suggest two distinct routes of rumen fluke introduction into this area. This approach has wider applicability for investigations of the origin of rumen fluke infections and for the possibility of parasite transmission at the livestock-wildlife interface. PMID:27043709

  1. Prevalence and Sequence-Based Identity of Rumen Fluke in Cattle and Deer in New Caledonia

    PubMed Central

    Cauquil, Laura; Hüe, Thomas; Hurlin, Jean-Claude; Mitchell, Gillian; Searle, Kate; Skuce, Philip; Zadoks, Ruth

    2016-01-01

    An abattoir survey was performed in the French Melanesian archipelago of New Caledonia to determine the prevalence of paramphistomes in cattle and deer and to generate material for molecular typing at species and subspecies level. Prevalence in adult cattle was high at animal level (70% of 387 adult cattle) and batch level (81%). Prevalence was lower in calves at both levels (33% of 484 calves, 51% at batch level). Animals from 2 of 7 deer farms were positive for rumen fluke, with animal-level prevalence of 41.4% (29/70) and 47.1% (33/70), respectively. Using ITS-2 sequencing, 3 species of paramphistomes were identified, i.e. Calicophoron calicophorum, Fischoederius elongatus and Orthocoelium streptocoelium. All three species were detected in cattle as well as deer, suggesting the possibility of rumen fluke transmission between the two host species. Based on heterogeneity in ITS-2 sequences, the C. calicophorum population comprises two clades, both of which occur in cattle as well as deer. The results suggest two distinct routes of rumen fluke introduction into this area. This approach has wider applicability for investigations of the origin of rumen fluke infections and for the possibility of parasite transmission at the livestock-wildlife interface. PMID:27043709

  2. Fasciola hepatica: antibody coating of juvenile flukes in the intestinal lumen of resistant rats.

    PubMed

    Burden, D J; Hughes, D L; Hammet, N C

    1982-01-01

    Newly excysted juvenile Fasciola hepatica, when placed in isolated loops of intestine prepared in previously infected rats, acquired a surface covering of rat immunoglobulin. IgG, IgA, IgE and IgM were all involved. This immunoglobulin coating was sloughed off when the flukes were maintained in vitro for three hours. PMID:7045997

  3. Severe biliary hyperplasia associated with liver fluke infection in an adult alpaca.

    PubMed

    Hamir, A N; Smith, B B

    2002-09-01

    An adult alpaca (Lama pacos) had a locally extensive area of hepatic atrophy involving the right lobe. Grossly, the atrophic lobe was light tan and firm and contained small, raised, white to yellow, partially mineralized circular nodules predominantly at the periphery of the atrophic tissue. Microscopically, viable hepatocytes were not present in the atrophic area, and the tissue consisted of diffuse biliary epithelial proliferation without any evidence of nuclear or cellular atypia or the presence of mitotic figures. The circular mineralized nodules consisted of granulomatous inflammation with intralesional parasitic ova surrounded by fibrous connective tissue. Morphologically, the ova were compatible with those of Fasciola hepatica. The severe biliary hyperplasia was unusual, and it was not clear whether it was caused by an aberrant host response to the parasitic infection or whether it was an unrelated event. PMID:12243473

  4. Detection of the Carcinogenic Liver Fluke Opisthorchis viverrini Using a Mini Parasep SF Faecal Parasite Concentrator.

    PubMed

    Kaewpitoon, Soraya J; Rujirakul, Ratana; Tongtawee, Taweesak; Matrakul, Likit; Panpimanmas, Sukij; Wakkuwattapong, Parichart; Loyd, Ryan A; Kaewpitoon, Natthawut

    2016-01-01

    The Mini Parasep SF fecal parasite concentrator (MPSFC) is a new modification of the closed concentration system, which can easily be adopted in any routine clinical pathology laboratory. Here we describe our experience with the system in diagnosing Opisthorchis viverrini. A total of 199 fecal samples was submitted for routine examination in the clinical pathology laboratory of Suranaree University of Technology hospital, Nakhon Ratchasima province, Thailand, during August to October 2015. Out of all samples examined, 10 (5.03%) were positive with intestinal parasites including O. viverrini (2.01%), followed by Strongyloided stercoralis (1.51%), Hookworm (0.5%), Taenia spp. (0.5%), and Entamoeba coli (0.5%). Regarding the distribution of intestinal parasites in relation to the methods used, and found that 4 samples (2.01%) were positive using the direct wet smear method while 10 (5.03%) were positive with the Mini Parasep SF method; the difference was statistically significant (X2-test = 116.506, p-value =0.001). Mean time for processing using the Parasep system was 6.03 min/ sample, the conventional direct wet smear method at 0.3 min/sample. Cost per test, conventional direct wet smear method costing less than the Parasep method at USD 0.74/sample versus USD 1.47/sample. This first report of O. viverrini detection using MPSFC indicates that Parasep concentration test is useful in the routine laboratory, increasing the yield of parasites as compared to direct microscopy, but with greater processing time and cost. Further comparisons between the Parasep concentration test and common methods for O. viverrini detection are required, particularly concerning use in epidemiological surveys. PMID:26838241

  5. A native 13-kDa fatty acid binding protein from the liver fluke Fasciola hepatica.

    PubMed

    Timanova-Atanasova, Anna; Jordanova, Rosita; Radoslavov, Georgi; Deevska, Gergana; Bankov, Ilia; Barrett, John

    2004-09-24

    A 13-kDa fatty acid binding protein (FABP) (Fh13) has been isolated from the cytosol of adult Fasciola hepatica and its physicochemical and binding characteristics determined. Fh13 appears to exist as a dimer in native solution. Binding of the fluorescent fatty acid analogue 11-((5-dimethyl aminonaphthalene-1-sulfonyl) amino) undecanoic acid (DAUDA) to Fh13 results in changes in the emission spectrum, which are reversed by oleic acid. The binding activity for DAUDA determined from titration experiments revealed a single binding site per monomeric unit with Kd of 1.5 microM. The displacement of DAUDA by competitive nonfluorescent ligands allowed Kd values for oleic (2.5 microM), retinoic (2.8 microM), palmitic (4.1 microM) and arachidonic acid (6.1 microM) to be calculated. Ten commonly used anthelmintics were evaluated for binding to Fh13, but only bithionol showed binding activity commensurate with those of the putative natural ligands (Kd 6.8 microM). PMID:15374624

  6. Aberrant Expression of NF-κB in Liver Fluke Associated Cholangiocarcinoma: Implications for Targeted Therapy

    PubMed Central

    Seubwai, Wunchana; Wongkham, Chaisiri; Puapairoj, Anucha; Khuntikeo, Narong; Pugkhem, Ake; Hahnvajanawong, Chariya; Chaiyagool, Jariya; Umezawa, Kazuo; Okada, Seiji; Wongkham, Sopit

    2014-01-01

    Background Up-regulation and association of nuclear factor kappa B (NF-κB) with carcinogenesis and tumor progression has been reported in several malignancies. In the current study, expression of NF-κB in cholangiocarcinoma (CCA) patient tissues and its clinical significance were determined. The possibility of using NF-κB as the therapeutic target of CCA was demonstrated. Methodology Expression of NF-κB in CCA patient tissues was determined using immunohistochemistry. Dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor, was used to inhibit NF-κB action. Cell growth was determined using an MTT assay, and cell apoptosis was shown by DNA fragmentation, flow cytometry and immunocytofluorescent staining. Effects of DHMEQ on growth and apoptosis were demonstrated in CCA cell lines and CCA-inoculated mice. DHMEQ-induced apoptosis in patient tissues using a histoculture drug response assay was quantified by TUNEL assay. Principal Findings Normal bile duct epithelia rarely expressed NF-κB (subunits p50, p52 and p65), whereas all CCA patient tissues (n  =  48) over-expressed all NF-κB subunits. Inhibiting NF-κB action by DHMEQ significantly inhibited growth of human CCA cell lines in a dose- and time-dependent manner. DHMEQ increased cell apoptosis by decreasing the anti-apoptotic protein expressions–Bcl-2, XIAP–and activating caspase pathway. DHMEQ effectively reduced tumor size in CCA-inoculated mice and induced cell apoptosis in primary histocultures of CCA patient tissues. Conclusions NF-κB was over-expressed in CCA tissues. Inhibition of NF-κB action significantly reduced cell growth and enhanced cell apoptosis. This study highlights NF-κB as a molecular target for CCA therapy. PMID:25170898

  7. Comparative Characterization of MicroRNAs from the Liver Flukes Fasciola gigantica and F. hepatica

    PubMed Central

    Fu, Jing-Hua; Nisbet, Alasdair J.; Liu, Qing-You; Chen, Mu-Xin; Zhou, Dong-Hui; Zhu, Xing-Quan

    2012-01-01

    MicroRNAs (miRNAs) are key regulators of gene expression at the post-transcription level. The present study specifically explored and compared the miRNA expression profiles of F. gigantica and F. hepatica using an integrated sequencing and bioinformatics platform and quantitative real-time PCR. Nineteen and 16 miRNA candidates were identified from F. gigantica and F. hepatica, respectively. The two parasites shared 11 miRNAs, with 8 also showing similarity to miRNAs of Schistosoma japonicum. Another 8 miRNAs were identified as F. gigantica-specific and 5 as F. hepatica-specific, most of which were novel. Predicted target analysis with 11465 mRNA and EST sequences of F. hepatica and F. gigantica revealed that all of the miRNAs had more than one target, ranging from 2 to 398 with an average of 51 targets. Some functions of the predicted targets were only found in F. gigantica, such as “transcription regulator”, while some others were only found in F. hepatica, such as “reproduction” and “response to stimulus”, indicating the different metabolism and gene regulation patterns of the two parasites. The present study represents the first global comparative characterization of miRNA expression profiles of F. gigantica and F. hepatica, which has provided novel valuable resources for a better understanding of the two zoonotic trematodes. PMID:23300925

  8. Combined effects of social stress and liver fluke infection in a mouse model.

    PubMed

    Avgustinovich, Damira F; Marenina, Mariya K; Zhanaeva, Svetlana Ya; Tenditnik, Mikhail V; Katokhin, Alexey V; Pavlov, Konstantin S; Sivkov, Anton Yu; Vishnivetskaya, Galina B; Lvova, Maria N; Tolstikova, Tatiana G; Mordvinov, Viatcheslav A

    2016-03-01

    The effects of two influences, social stress and acute opisthorchiasis, were investigated in inbred C57BL/6J male mice. In the model of social stress, mice were repeatedly attacked and defeated by aggressive outbred ICR male mice and were in continuous sensory contact with an aggressive conspecific mouse in their home cage for 20days. Acute opisthorchiasis was provoked by invasion of Opisthorchis felineus (50 larvae per animal) on the fourth day after the social stress was induced. Simultaneous action of both factors caused the hypertrophy of adrenal glands, as well as elevated the activity of cathepsins B and L in the spleen. This effect on the activity of the cysteine proteases in the hippocampus and hypothalamus following O. felineus invasion was the predominant result of simultaneous action with social stress. Acute opisthorchiasis, social stress, and their combination caused an increase in the level of blood IL-6 in approximately 30% of the animals. Social stress induced a more pronounced effect on mouse plus-maze behavior than O. felineus invasion. Our results suggest a more severe negative effect of the simultaneous influence of both factors on most of the parameters that were investigated. PMID:26778779

  9. Ultrastructural investigations on the effects of praziquantel on human trematodes from Asia: Clonorchis sinensis, Metagonimus yokogawai, Opisthorchis viverrini, Paragonimus westermani and Schistosoma japonicum.

    PubMed

    Mehlhorn, H; Kojima, S; Rim, H J; Ruenwongsa, P; Andrews, P; Thomas, H; Bunnag, B

    1983-01-01

    The effect of praziquantel (Biltricide) on the ultrastructure of trematodes pathogenic to man in Asia was investigated in: Clonorchis sinensis, Opisthorchis viverrini, Schistosoma japonicum, Metagonimus yokogawai, and Paragonimus westermani. The different parasites were isolated from their respective experimental hosts and uniformly incubated for 5, 15, 30 or 60 min at 37 degrees C in medium TC 199 containing 0, 1, 10 or 100 micrograms praziquantel/ml. All parasites exposed to praziquantel were contracted and displayed tegumental alterations. 1. Clonorchis sinensis, Opisthorchis viverrini and Schistosoma japonicum reacted with severe tegumental vacuolisation within 5 min after exposure to 1 microgram praziquantel/ml. The extent of the damage induced increased with exposure time. 2. In vivo treated Opisthorchis viverrini worms had the same damages as in vitro treated ones. 3. Metagonimus yokogawai displayed the same degree of vacuolisation after exposure to all concentrations of praziquantel. Complete destruction of the tegumental surface was not achieved, however, possibly because of the presence of numerous tegumental hooks. 4. Paragonimus westermani was least sensitive to praziquantel. Only very few vacuoles were formed after incubation in 100 micrograms/ml for 60 min. It is assumed that the very dense texture of the thick tegument is responsible for the relative refractoriness to praziquantel in vitro. However, in vivo the parasite is successfully eliminated by praziquantel. PMID:6338885

  10. Fasciola hepatica: attempts to immunise rats and mice with metabolic and somatic antigens derived from juvenile flukes.

    PubMed

    Burden, D J; Harness, E; Hammet, N C

    1982-02-01

    Attempts were made to vaccinate rats and mice against Fasciola hepatica using either somatic or metabolic antigens derived from juvenile flukes between 10 and 16 days old. None of the regimes tried induced a good resistance to subsequent infection, though metabolic antigens derived from 13-14-day-old flukes when injected subcutaneously into rats with adjuvant did produce some protection to challenge. PMID:7201201

  11. Phyllodistomum kanae sp. nov. (Trematoda: Gorgoderidae), a bladder fluke from the Ezo salamander Hynobius retardatus.

    PubMed

    Nakao, Minoru

    2015-10-01

    The Ezo salamander, Hynobius retardatus, is endemic only to Hokkaido, the northernmost island of Japan. Gravid flukes of the family Gorgoderidae were discovered from the urinary bladder of H. retardatus. The parasites were identified as a new species named Phyllodistomum kanae sp. nov. In the neighboring Honshu island another bladder fluke, Phyllodistomum patellare, has already been found from the Japanese newt. The new species clearly differs from P. patellare in having a spherical ovary and very weakly lobed testes. The discovery of species of Phyllodistomum from urodelan amphibians is very uncommon in Eurasia. A molecular phylogeny based on 28S ribosomal DNA suggests that sphaeriid bivalves may serve as the first intermediate host for the new species. PMID:25892565

  12. The Observational Problem of Whether Life on Earth is a Fluke

    NASA Astrophysics Data System (ADS)

    Woolf, N. J.

    1998-12-01

    The presence of life on Earth could be the result of such a rare accident, so that life far from Earth would be exceedingly rare. The issue arises because the simplest known life forms are exceedingly complex, the apparent result of a long line of chemical and biological evolution. We know that life was relatively abundant on Earth not long after the last ocean-destroying collision occurred here. But this alone does not tell us whether or not in the development of life there was some extremely improbable step or steps. Whether life here was the result of such a fluke or flukes is susceptible to two lines of study, one observational, the other experimental. In the experimental method, one attempts to create very simple life forms. But it is by no means certain that human experimental ability is as good as nature's. The observational approach has three current facets, looking for microbial life elsewhere in the solar system, looking for chemical tracers of life in other planetary systems and looking for the communications of extra-terrestrial intelligences. All three are discussed at this meeting by Chyba, Beichman and Tarter. The discovery of life elsewhere in the solar system does not exclude a fluke -- if panspermia works within the solar system, we could all be Martians, Europans etc. in origin, and the fluke might have occurred there. If panspermia works between different planetary systems, then at best we are looking to see whether life exists with both forms of handedness, which would demonstrate that life developed at least twice, and such a test would require an interstellar vehicle. The study of chemical tracers and communications are searches designed against false positives. This paper explores the implications that would be associated with positive results from observations.

  13. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic ... Almost any cancer can spread to the liver. Cancers that can spread to the liver include: Breast cancer Colorectal cancer Esophageal ...

  14. Differential Activation of Diverse Glutathione Transferases of Clonorchis sinensis in Response to the Host Bile and Oxidative Stressors

    PubMed Central

    Bae, Young-An; Ahn, Do-Whan; Lee, Eung-Goo; Kim, Seon-Hee; Cai, Guo-Bin; Kang, Insug; Sohn, Woon-Mok; Kong, Yoon

    2013-01-01

    Background Clonorchis sinensis causes chronic cumulative infections in the human hepatobiliary tract and is intimately associated with cholangiocarcinoma. Approximately 35 million people are infected and 600 million people are at risk of infections worldwide. C. sinensis excretory-secretory products (ESP) constitute the first-line effector system affecting the host-parasite interrelationship by interacting with bile fluids and ductal epithelium. However, the secretory behavior of C. sinensis in an environment close to natural host conditions is unclear. C. sinensis differs from Fasciola hepatica in migration to, and maturation in, the hepatic bile duct, implying that protein profile of the ESP of these two trematodes might be different from each other. Methodology/Principal Findings We conducted systemic approaches to analyze the C. sinensis ESP proteome and the biological reactivity of C. sinensis glutathione transferases (GSTs), such as global expression patterns and induction profiles under oxidative stress and host bile. When we observed ex host excretion behavior of C. sinensis in the presence of 10% host bile, the global proteome pattern was not significantly altered, but the amount of secretory proteins was increased by approximately 3.5-fold. Bioactive molecules secreted by C. sinensis revealed universal/unique features in relation to its intraluminal hydrophobic residing niche. A total of 38 protein spots identified abundantly included enzymes involved in glucose metabolism (11 spots, 28.9%) and diverse-classes of glutathione transferases (GSTs; 10 spots, 26.3%). Cathepsin L/F (four spots, 10.5%) and transporter molecules (three spots, 7.9%) were also recognized. The universal secretory proteins found in other parasites, such as several enzymes involved in glucose metabolism and oxygen transporters, were commonly detected. C. sinensis secreted less cysteine proteases and fatty acid binding proteins compared to other tissue-invading or intravascular trematodes. Interestingly, secretion of a 28 kDa σ-class GST (Cs28σGST3) was significantly affected by the host bile, involving reduced secretion of the 28 kDa species and augmented secretion of Cs28σGST3-related high-molecular-weight 85 kDa protein. Oxidative stressors induced upregulated secretion of 28 kDa Cs28σGST3, but not an 85 kDa species. A secretory 26 kDa μ-class GST (Cs26μGST2) was increased upon treatment with oxidative stressors and bile juice, while another 28 kDa σ-class GST (Cs28σGST1) showed negligible responses. Conclusions/Significance Our results represent the first analysis of the genuine nature of the C. sinensis ESP proteome in the presence of host bile mimicking the natural host environments. The behavioral patterns of migration and maturation of C. sinensis in the bile ducts might contribute to the secretion of copious amounts of diverse GSTs, but a smaller quantity and fewer kinds of cysteine proteases. The Cs28σGST1 and its paralog(s) detoxify endogenous oxidative molecules, while Cs28σGST3 and Cs26μGST2 conjugate xenobiotics/hydrophobic substances in the extracellular environments, which imply that diverse C. sinensis GSTs might have evolved for each of the multiple specialized functions. PMID:23696907

  15. A comparison of the efficacy of doramectin, closantel and levamisole in the treatment of the 'oriental eye fluke', Philophthalmus gralli, in commercially reared ostriches (Struthio camelus).

    PubMed

    Mukaratirwa, S; Chimbwanda, M; Matekwe, N; Matenga, E

    2008-06-01

    Commercially reared ostriches at Msengi farm situated in the Chinhoyi area of Mashonaland West province in Zimbabwe were found to be infected with the 'oriental eye fluke', Philopthalmus gralli, in 2001. This was the ist record of the fluke in Zimbabwe. Trials were conducted to identify a suitable drug for the treatment of this fluke. A total of 12 ostriches confirmed to be infected with the fluke through clinical examination of the eyes and identification of the fluke were randomly divided into 3 equal groups, with each group receiving a different treatment protocol. The 3 drugs used were doramectin, levamisole and closantel. Each of the drugs was used in combination with chloramphenicol as an eye ointment. Levamisole was administered topically into the eye whereas doramectin and closantel were administered parenterally as an intramuscular injection. The results indicated a positive response in levamisole-treated birds but there were no noticeable responses to doramectin and closantel treatments. PMID:18846856

  16. Fasciola hepatica: Histology of the Reproductive Organs and Differential Effects of Triclabendazole on Drug-Sensitive and Drug-Resistant Fluke Isolates and on Flukes from Selected Field Cases

    PubMed Central

    Hanna, Robert

    2015-01-01

    This review summarises the findings of a series of studies in which the histological changes, induced in the reproductive system of Fasciola hepatica following treatment of the ovine host with the anthelmintic triclabendazole (TCBZ), were examined. A detailed description of the normal macroscopic arrangement and histological features of the testes, ovary, vitelline tissue, Mehlis’ gland and uterus is provided to aid recognition of the drug-induced lesions, and to provide a basic model to inform similar toxicological studies on F. hepatica in the future. The production of spermatozoa and egg components represents the main energy consuming activity of the adult fluke. Thus the reproductive organs, with their high turnover of cells and secretory products, are uniquely sensitive to metabolic inhibition and sub-cellular disorganisation induced by extraneous toxic compounds. The flukes chosen for study were derived from TCBZ-sensitive (TCBZ-S) and TCBZ-resistant (TCBZ-R) isolates, the status of which had previously been proven in controlled clinical trials. For comparison, flukes collected from flocks where TCBZ resistance had been diagnosed by coprological methods, and from a dairy farm with no history of TCBZ use, were also examined. The macroscopic arrangement of the reproductive system in flukes was studied using catechol/carmine stained whole mounts, and the histology of the main organs was examined using conventional haematoxylin-eosin stained sections. Validation of apoptosis in the fluke sections was carried out using an in situ hybridisation method designed to label endonuclease-induced DNA strand breaks. In TCBZ-S flukes exposed to TCBZ metabolites for 24–96 h in vivo, but not in TCBZ-R flukes, those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), were found to display progressive loss of cell content. This was due to apparent failure of cell division to keep pace with expulsion of the mature or effete products. Further, actively dividing cell types tended to become individualised, rounded and condensed, characteristic of apoptotic cell death. In the treated TCBZ-S flukes, strong positive labelling indicating apoptosis was associated with the morphologically abnormal cells undergoing mitosis or meiosis in the testis, ovary and vitelline follicles. In treated flukes from field outbreaks of suspected TCBZ-R fasciolosis, no significant histological changes were observed, nor was there any positive labelling for apotosis. On the other hand, sections of TCBZ treated flukes derived from a field case of fasciolosis where TCBZ resistance was not suspected displayed severe histological lesions, and heavy positive labelling for apoptosis. The triggering of apoptosis is considered to be related to failure of spindle formation at cell division, supporting the contention that TCBZ inhibits microtubule formation. In treated TCBZ-S flukes, protein synthesis and transport was apparently inhibited in the Mehlis’ secretory cells, perhaps due to energy uncoupling or to microtubule defects. In the uterus, successful formation of shelled eggs represents the culmination of a complex sequence of cytokinetic, cytological and synthetic activity involving the vitelline follicles, the ovary and the Mehlis’ gland. Histological evidence indicating failure of ovigenesis in TCBZ-S flukes was evident from as early as 24 h post-treatment onwards. Light labelling for apoptosis was associated with the testis of untreated Cullompton (TCBZ-S) and Sligo type 2 (TCBZ-R) flukes, which exhibit abnormal spermatogenesis and spermiogenesis, respectively. This was attributed to apoptosis and to heterophagy of effete germ line cells by the sustentacular tissue. The studies summarised in this review illustrate the potential utility of histological techniques for conveniently screening representative samples of flukes in field trials designed to validate instances of drug resistance. Histology can also be used to test the efficacy of new products against known drug-resistant and drug-susceptible fluke isolates. The account also provides reference criteria for drug-induced histopathological changes in fluke reproductive structures, examination of which may supplement and augment conventional coprological testing, and aid interpretation of TEM findings. PMID:26131614

  17. Eye fluke infection status in Baltic cod, Gadus morhua, after three decades and their use as ecological indicators.

    PubMed

    Mehrdana, Foojan; Marana, Moonika H; Skov, Jakob; Bahlool, Qusay Z M; Sindberg, Diana; Mundeling, Mai; Overgaard, Bettina C; Kania, Per W; Buchmann, Kurt

    2015-09-01

    Eye flukes of the genus Diplostomum were recorded with a prevalence of 7.4% and a mean intensity of 11.9 (range 1-75) parasites per fish in eye lenses of a total of 188 Atlantic cod, Gadus morhua, sampled in the Southeastern Baltic Sea from March 2013 to February 2014. A slight decrease of infection level, among the fish with body length ranging from 30 to 89.5 cm, was found when data were compared to a corresponding survey in the 1980s. Due to imprecise species identification of eye flukes based on morphometric analyses we present, as a baseline for further studies, rDNA sequences from a subsample of 19 eye flukes based on sequencing of a part of 18S, ITS-1, 5.8S, ITS-2 and part of 28S. We discuss the use of eye fluke recordings in Baltic cod as an environmental indicator due to the dependence of the parasite's life cycle on biotic (occurrence of snail and bird hosts) and abiotic (temperature and salinity) parameters. PMID:26204178

  18. Antibodies against Clonorchis sinensis LDH could cross-react with LDHB localizing on the plasma membrane of human hepatocarcinoma cell SMMC-7721 and induce apoptosis.

    PubMed

    Song, Tianzhang; Gan, Wenjia; Chen, Jintao; Huang, Lilin; Yin, Hongling; He, Tailong; Huang, Huaiqiu; Hu, Xuchu

    2016-04-01

    Lactate dehydrogenase (LDH) is a terminal enzyme in anaerobic glycolytic pathway. It widely exists in various organisms and is in charge of converting the glycolysis product pyruvic acid to lactic acid. Most parasites, including Clonorchis sinensis, predominantly depend on glycolysis to provide energy. Bioinformatic analysis predicts that the LDHs from many species have more than one transmembrane region, suggesting that it may be a membrane protein. C. sinensis LDH (CsLDH) has been confirmed as a transmembrane protein mainly located in the tegument. The antibodies against CsLDH can inhibit the worm's energy metabolism, kill the worm, and may have the same effects on human cancer cells. In this study, we cloned and characterized human LDHA (HsLDHA), HsLDHB, and CsLDH. Semi-quantitative real-time RCP showed that HsLDHB only existed in hepatocarcinoma cell SMMC-7721. Confocal microscopy and Western blot experiments revealed that HsLDHB was localized in the plasma membrane of SMMC-7721 cells, and the antibodies against CsLDH could cross-react with it. This cross-reaction could inhibit the enzymatic activity of HsLDHB. The cancer cells co-cultured with anti-CsLDH sera showed a significant decrease in cell proliferation rate and increases in caspase 9 and reactive oxygen species (ROS) levels. Therefore, anti-CsLDH antibodies can induce the apoptosis of cancer cells SMMC-7721 and may serve as a new tool to inhibit tumor. PMID:26769711

  19. Fasciola hepatica infection in sheep: changes in liver metabolism.

    PubMed

    Lenton, L M; Bygrave, F L; Behm, C A; Boray, J C

    1996-09-01

    Several aspects of liver function during infection with Fasciola hepatica were examined in sheep four weeks after infection and compared with the changes observed in infected rats. Previously reported respiratory abnormalities in mitochondria isolated from the left lobe of the liver of infected sheep were characterised further. Evidence is presented that the respiratory lesion is located in the mitochondrial electron transport chain and that the aberrant respiratory behaviour is not associated with an increase in nonesterified fatty acids and the depletion of mitochondrial phospholipids, as is the case in the rat. Microsomal membranes, which have also been shown to be depleted of phospholipids in the fluke-infected rat liver, showed no such changes in the sheep. However, in common with the rat, a substantial loss of cytochrome P450 was recorded in microsomes prepared from the left lobe, and the glycogen content of the left lobe was found to be less than 50 per cent of control values. No change was observed in glucose 6-phosphatase activity. All these changes were localised effects, confined to areas of fluke infiltration. PMID:8880986

  20. Characteristics and molecular phylogeny of Fasciola flukes from Bangladesh, determined based on spermatogenesis and nuclear and mitochondrial DNA analyses.

    PubMed

    Mohanta, Uday Kumar; Ichikawa-Seki, Madoka; Shoriki, Takuya; Katakura, Ken; Itagaki, Tadashi

    2014-07-01

    This study aimed to precisely discriminate Fasciola spp. based on DNA sequences of nuclear internal transcribed spacer 1 (ITS1) and mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 (nad1) gene. We collected 150 adult flukes from the bile ducts of cattle, buffaloes, sheep, and goats from six different regions of Bangladesh. Spermatogenic status was determined by analyzing stained seminal vesicles. The ITS1 types were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The nad1 haplotypes were identified based on PCR and direct sequencing and analyzed phylogenetically by comparing with nad1 haplotypes of Fasciola spp. from other Asian countries. Of the 127 aspermic flukes, 98 were identified as Fg type in ITS1, whereas 29 were identified as Fh/Fg type, indicating a combination of ITS1 sequences of Fasciola hepatica and Fasciola gigantica. All the 127 aspermic flukes showed Fsp-NDI-Bd11 in nad1 haplotype with nucleotide sequences identical to aspermic Fasciola sp. from Asian countries. Further, 20 spermic flukes were identified as F. gigantica based on their spermatogenic status and Fg type in ITS1. F. gigantica population was thought to be introduced into Bangladesh considerably earlier than the aspermic Fasciola sp. because 11 haplotypes with high haplotype diversity were detected from the F. gigantica population. However, three flukes from Bangladesh could not be precisely identified, because their spermatogenic status, ITS1 types, and nad1 haplotypes were ambiguous. Therefore, developing a robust method to distinguish aspermic Fasciola sp. from other Fasciola species is necessary in the future. PMID:24781019

  1. Eosinophilic proliferative pylephlebitis in the liver of Japanese beef cattle with fascioliasis.

    PubMed

    Tanimoto, T; Shirota, K; Ohtsuki, Y; Araki, K

    1998-10-01

    Intrahepatic pylephlebitis was detected in 17 Japanese beef cattle. Grossly, the intrahepatic vessels in the caudate lobe and/or in the periphery of the other hepatic lobes were thickened and protruded above the lobar surface. The vessel lumina were packed with white to red, waste thread-like contents. A few immature flukes were found in the bile ducts in 3 of the 7 cases with biliary thickening. Foci of hepatic necrosis and hemorrhage were scattered around the thickened vessels in 8 cases. Histologically, the interlobular veins were thickened due to severe intimal hyperplasia with endothelial proliferation and eosinophilic accumulation and medial hypertrophy, accompanied by fibrosis and eosinophilic infiltration in the portal areas. Hepatic tissues with necrosis and hemorrhage were surrounded by eosinophils and histiocytes including a granulomatous reaction. One immature fluke was detected in one of these regions of necrosis. Immunoperoxidase staining revealed that the small fluke, Kupffer cells, and histiocytes in the liver of all cases were positively stained with anti-Japanese Fasciola sp. antiserum. Enzyme-linked immunosorbent assay of the sera of 15 cases revealed that all were positive for the anti-Fasciola antibody. On the basis of these findings, the present cases were regarded as an atypical form of fascioliasis, characterized by eosinophilic proliferative pylephlebitis of the liver. PMID:9819759

  2. Pathological changes in cattle naturally infected by Calicophoron daubneyi adult flukes.

    PubMed

    Fuertes, Miguel; Pérez, Valentín; Benavides, Julio; González-Lanza, M Camino; Mezo, Mercedes; González-Warleta, Marta; Giráldez, Francisco Javier; Fernández, Miguel; Manga-González, M Yolanda; Ferreras, M Carmen

    2015-04-30

    Local host response and parasite distribution were studied in the forestomachs, abomasum, duodenum and regional lymph nodes of cattle suffering from bovine paramphistomosis. The parasites were found attached, by its ventral sucker, to small conical papillae of the rumen and reticulum. Affected papillae, showed morphological changes denoted by very narrow stalks and expanded heads. Histologically, these changes were characterized by epithelial acanthosis-hyperkeratosis of the epithelium. Infiltration of inflammatory cells was often related with the epithelial changes, although it was also found in the duodenal mucosa and submucosa. These cells were arranged as aggregates or follicles but sparse infiltration of eosinophils, globule leukocytes, mast cells or macrophages was also observed in the lamina propria. Tissue damage and inflammatory reaction were more severe in the ruminal atrium, where the largest number of flukes and affected papillae were observed. In contrast, lesions in the ruminal dorsal sac were absent or mild. Statistical correlation between lesion severity and parasite burden was confirmed. PMID:25801360

  3. Risk factors for Opisthorchis viverrini and minute intestinal fluke infections in Lao PDR, 2009-2011.

    PubMed

    Yoon, Hee Jung; Ki, Moran; Eom, Keeseon; Yong, Tai-Soon; Chai, Jong-Yil; Min, Duk-Young; Rim, Han-Jong; Sohn, Woon-Mok; Insisiengmay, Bounnaloth; Phommasack, Bounlay

    2014-08-01

    The purpose of this report is to compare the prevalence of Opisthorchis viverrini/minute intestinal fluke (Ov/MIF) in Lao People's Democratic Republic according to different regions and evaluate the effect of ingestion of raw freshwater fish on the infection. Demographic data, behavioral data, and symptoms were obtained, and the Kato-Katz method was used for the diagnosis of Ov/MIF. In total, 3,046 individuals were enrolled. The risk factors associated with acquisition of Ov/MIF were raw fish consumption and province. Khong Island showed the highest prevalence (odds ratio = 80.1, 95% confidence interval = 47.9-133.9, P < 0.001) compared with other districts, and raw fish consumption was related to Ov/MIF infection. Administration of praziquantel to entire populations, education (avoiding consumption of raw food dishes and improved hygiene), and access to clean water and sanitation should be considered. PMID:24980495

  4. Risk Factors for Opisthorchis viverrini and Minute Intestinal Fluke Infections in Lao PDR, 2009–2011

    PubMed Central

    Yoon, Hee Jung; Ki, Moran; Eom, Keeseon; Yong, Tai-Soon; Chai, Jong-Yil; Min, Duk-Young; Rim, Han-Jong; Sohn, Woon-Mok; Insisiengmay, Bounnaloth; Phommasack, Bounlay

    2014-01-01

    The purpose of this report is to compare the prevalence of Opisthorchis viverrini/minute intestinal fluke (Ov/MIF) in Lao People's Democratic Republic according to different regions and evaluate the effect of ingestion of raw freshwater fish on the infection. Demographic data, behavioral data, and symptoms were obtained, and the Kato–Katz method was used for the diagnosis of Ov/MIF. In total, 3,046 individuals were enrolled. The risk factors associated with acquisition of Ov/MIF were raw fish consumption and province. Khong Island showed the highest prevalence (odds ratio = 80.1, 95% confidence interval = 47.9–133.9, P < 0.001) compared with other districts, and raw fish consumption was related to Ov/MIF infection. Administration of praziquantel to entire populations, education (avoiding consumption of raw food dishes and improved hygiene), and access to clean water and sanitation should be considered. PMID:24980495

  5. Liver Wellness

    MedlinePlus

    ... disease. • Some liver diseases such as hepatitis A, hepatitis B, hepatitis C, fatty liver disease, NASH, and alcohol- ... prevented. • There are vaccines for hepatitis A and hepatitis B. American Liver Foundation www.liverfoundation.org 1-800- ...

  6. Liver biopsy

    MedlinePlus

    ... cancer. This test also may be performed for: Alcoholic liver disease (fatty liver, hepatitis, or cirrhosis) Amebic ... C Hepatitis D Hepatocellular carcinoma Hodgkin's lymphoma Non-alcoholic fatty liver disease Non-Hodgkin's lymphoma Primary biliary ...

  7. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  8. Transcriptome analysis of the adult rumen fluke Paramphistomum cervi following next generation sequencing.

    PubMed

    Choudhary, Vijayata; Garg, Sweta; Chourasia, Reetika; Hasnani, J J; Patel, P V; Shah, Tejas M; Bhatt, Vaibhav D; Mohapatra, Amitbikram; Blake, Damer P; Joshi, Chaitanya G

    2015-10-01

    Rumen flukes are parasitic trematodes (Platyhelminthes: Digenea) of major socioeconomic importance in many countries. Key representatives, such as Paramphistomum cervi, can cause "Rumen fluke disease" or paramphistomosis and undermine economic animal productivity and welfare. P. cervi is primarily a problem in sheep, goat and buffalo production as a consequence of reduced weight gain and milk production, clinical disease or death. Recent technological advances in genomics and bioinformatics now provide unique opportunities for the identification and pre-validation of drug targets and vaccines through improved understanding of the biology of pathogens such as P. cervi and their relationship with their hosts at the molecular level. Here, we report next generation transcriptome sequencing analysis for P. cervi. RNAseq libraries were generated from RNA extracted from 15 adult P. cervi parasites sampled from each of three different host species (sheep, goat and buffalo) and a reference transcriptome was generated by assembly of all Ion Torrent PGM sequencing data. Raw reads (7,433,721 in total) were initially filtered for host nucleotide contamination and ribosomal RNAs and the remaining reads were assembled into 43,753 high confidence transcript contigs. In excess of 50% of the assembled transcripts were annotated with domain- or protein sequence similarity derived functional information. The reference adult P. cervi transcriptome will serve as a basis for future work on the biology of this important parasite. Using the widely investigated trematode virulence factor and vaccine candidate Cathepsin L as an example, the epitope GPISIAINA was found to be conserved in P. cervi isolated from three different host species supporting its candidacy for vaccine development and illustrating the utility of the adult P. cervi transcriptome. PMID:26049095

  9. Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells

    PubMed Central

    He, Lei; Wang, Xiaoyun; Liang, Pei; Chen, Wenjun; Bian, Meng; Ren, Mengyu; Lin, Jinsi; Liang, Chi; Xu, Jin; Wu, Zhongdao; Li, Xuerong; Huang, Yan; Yu, Xinbing

    2013-01-01

    Background Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC). It has been well known that the excretory/secretory products of C. sinensis (CsESPs) play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin), which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell. Methodology/Principal Findings There was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin) and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h. Conclusions/Significance Collectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the process of HCC patients combined with C. sinensis infection. PMID:24367717

  10. Factors affecting abundance and prevalence of blood fluke, Cardicola forsteri, infection in commercially ranched southern bluefin tuna, Thunnus maccoyii, in Australia.

    PubMed

    Aiken, Hamish M; Hayward, Craig J; Nowak, Barbara F

    2015-05-30

    A survey of blood fluke, Cardicola forsteri, infection in ranched southern bluefin tuna, Thunnus maccoyii, was undertaken over three farming seasons, from March 2004 to September 2006. Analyses of covariance and logistic regression were used to explore the effects of company, year, season, time in culture, and condition index on intensity, abundance and prevalence of blood fluke infection. Average prevalence of blood fluke infection was 62.64% over the period of the survey. Average intensity was 6.20 (± 0.57) fluke per infected host and the average abundance was 3.70 (± 0.57) fluke per host. Year did not influence mean intensity or abundance although a significant decrease in prevalence in 2005 was evident. Tuna harvested in winter had a significantly greater abundance and prevalence of blood fluke than the tuna harvested in autumn. No effect of intensity or abundance of infection was observed on the condition of the infected tuna. A universal factor in explaining variation in C. forsteri intensity, abundance and prevalence was company. Differences in infection levels between tuna from different companies may be related to differences in husbandry measures employed on each farm, or due to different average sizes of tuna farmed by each of the companies, or due to the location of the operations. PMID:25862423

  11. Clonorchiasis control: starting from awareness

    PubMed Central

    2014-01-01

    Clonorchiasis is caused by infection with food-borne liver fluke, namely Clonorchis sinensis, which is also considered to be a neglected tropical disease. It is estimated that over 10 million people are infected with C. sinensis in China and, subsequently, several thousand new cholangiocarcinoma cases occur annually. On May 18, 2014, China Central Television broadcasted an episode on the habit of raw-fish eating and its potential to cause clonorchiasis in a programme called Health on the tip of the tongue. Here, I briefly introduce the content of the episode and discuss its significance for clonorchiasis control in China. PMID:25243069

  12. Intervention to Improve the Quality of Life of a Bottlenose Dolphin That Developed Necrosis on the Tail Flukes

    PubMed Central

    Ueda, Keiichi; Murakami, Masahito; Kato, Junichi; Miyahara, Hirokazu; Izumisawa, Yasuharu

    2013-01-01

    [Purpose, Case, and Methods] A female bottlenose dolphin (Tursiops truncatus) in captivity developed necrosis of the tail flukes. Although the diseased site healed after surgical resection, the loss of approximately 75% of the tail greatly affected her swimming performance. To restore swimming ability, we developed artificial tail flukes as a prosthetic swimming aid and provided physical therapy that included swimming training from postoperative day 1 to day 1427. [Results] The prosthetic enabled the dolphin to recover swimming ability almost to the level prior to disease onset, but even acquire applied movement, and reestablish social relationships, thus greatly improving the animal's quality of life. [Conclusion] The results clearly demonstrate that, as in postoperative rehabilitation in humans, the use of prosthetic devices in physical therapy can be beneficial for marine animals such as dolphins. PMID:24259946

  13. Role of the lymnaeid snail Pseudosuccinea columella in the transmission of the liver fluke Fasciola hepatica in Egypt.

    PubMed

    Dar, Y; Vignoles, P; Rondelaud, D; Dreyfuss, G

    2015-11-01

    Experimental infections of three Egyptian Pseudosuccinea columella populations with sympatric miracidia of Fasciola sp., coming from cattle- or sheep-collected eggs, were carried out to determine the capacity of this lymnaeid to support larval development of the parasite. Using microsatellite markers, the isolates of Egyptian miracidia were identified as Fasciola hepatica. Apart from being independent of snail origin, prevalences ranging from 60.4 to 75.5% in snails infected with five miracidia of F. hepatica were significantly higher than values of 30.4 to 42.2% in snails with bi-miracidial infections. The number of metacercariae ranged from 243 to 472 per cercarial-shedding snail and was independent of snail origin, parasite origin and miracidial dose used for infection. If P. columella was subjected to two successive bi-miracidial infections with F. hepatica, prevalence of infection was 63.3%, with a mean of 311 metacercariae per snail. These values were clearly greater than those already reported for Radix natalensis infected with the same parasite and the same protocol. Successful experimental infection of P. columella with F. hepatica suggests that this lymnaeid snail is an important intermediate host for the transmission of fascioliasis in Egypt. PMID:24865184

  14. Pleural epitheliod hemangioendothelioma: What started as a liver fluke and ended up being almost mistaken for malignant mesothelioma

    PubMed Central

    Jamy, Omer H.; Huber, Bryan; Giri, Smith

    2015-01-01

    Epitheliod hemangioendothelioma (EHE) is a rare tumor of vascular origin. The pleural variant has only been reported around 20 times in English literature. It commonly occurs in older men and carries a poor prognosis with average survival lasting from a few weeks to months. Pleural EHE (PEHE) can be a diagnostic challenge due to its rarity as well as similarities to other pleural and vascular tumors. There is currently no standard treatment for EHE. Due to the rarity of this disease, reaching a final diagnosis is challenging. It's clinical, radiological, and pathological resemblance to malignant mesothelioma can cause a delay in diagnosis. Special stains such as CD31, CD34, and factor VIII related antigen can help differentiate between the two. Ordering appropriate stains in a timely manner can help avoid misdiagnosing PEHE. PMID:26664569

  15. Carcinogenic liver fluke Opistorchis viverrini oxysterols detected by LC-MS/MS survey of soluble fraction parasite extract

    PubMed Central

    Vale, Nuno; Gouveia, Maria João; Botelho, Mónica; Sripa, Banchob; Suttiprapa, Sutas; Rinaldi, Gabriel; Gomes, Paula; Brindley, Paul J.; da Costa, José Manuel Correia

    2013-01-01

    Liquid chromatography in tandem mass spectrometry (LC-MS/MS) has emerged as an informative tool to investigate oxysterols (oxidized derivatives of cholesterol) in helminth parasite associated cancers. Here, we used LC-MS/MS to investigate in soluble extracts of the adult developmental stage of O. viverrini from experimentally infected hamsters. Using comparisons with known bile acids and the metabolites of estrogens, the LC-MS data indicated the existence of novel oxysterol derivatives in O. viverrini. Most of these derivatives were ramified at C-17, in similar fashion to bile acids and their conjugated salts. Several were compatible with the presence of an estrogen core, and/or hydroxylation of the steroid aromatic ring A, hydroxylation of both C-2 and C-3 of the steroid ring and further oxidation into an estradiol-2,3-quinone. PMID:23973383

  16. Plasma IgG autoantibody against actin-related protein 3 in liver fluke Opisthorchis viverrini infection.

    PubMed

    Rucksaken, R; Haonon, O; Pinlaor, P; Pairojkul, C; Roytrakul, S; Yongvanit, P; Selmi, C; Pinlaor, S

    2015-07-01

    Opisthorchiasis secondary to Opisthorchis viverrini infection leads to cholangiocellular carcinoma through chronic inflammation of the bile ducts and possibly inducing autoimmunity. It was hypothesized that plasma autoantibodies directed against self-proteins are biomarkers for opisthorchiasis. Plasma from patients with opisthorchiasis was tested using proteins derived from immortalized cholangiocyte cell lines, and spots reacting with plasma were excised and subjected to LC-MS/MS. Seven protein spots were recognized by IgG autoantibodies, and the highest matching scored protein was actin-related protein 3 (ARP3). The antibody against ARP3 was tested in plasma from 55 O. viverrini-infected patients, 24 patients with others endemic parasitic infections and 17 healthy controls using Western blot and ELISA. Immunoreactivity against recombinant ARP3 was significantly more prevalent in opisthorchiasis compared to healthy controls at Western blotting and ELISA (P < 0.05). Plasma ARP3 autoantibody titres were also higher in opisthorchiasis compared to healthy individuals (P < 0.01) and other parasitic infections including Strongyloides stercoralis (P < 0.001), echinostome (P < 0.05), hookworms (P < 0.001) and Taenia spp. (P < 0.05). It was further characterized in that the ARP3 autoantibody titre had a sensitivity of 78.18% and specificity of 100% for opisthorchiasis. In conclusion, it may be suggested that plasma anti-ARP3 might represent a new diagnostic antibody for opisthorchiasis. PMID:25809205

  17. Liver Immunology

    PubMed Central

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  18. Co-dispersal of the blood fluke Schistosoma japonicum and Homo sapiens in the Neolithic Age

    PubMed Central

    Yin, Mingbo; Zheng, Hong-Xiang; Su, Jing; Feng, Zheng; McManus, Donald P.; Zhou, Xiao-Nong; Jin, Li; Hu, Wei

    2015-01-01

    The global spread of human infectious diseases is of considerable public health and biomedical interest. Little is known about the relationship between the distribution of ancient parasites and that of their human hosts. Schistosoma japonicum is one of the three major species of schistosome blood flukes causing the disease of schistosomiasis in humans. The parasite is prevalent in East and Southeast Asia, including the People’s Republic of China, the Philippines and Indonesia. We studied the co-expansion of S. japonicum and its human definitive host. Phylogenetic reconstruction based on complete mitochondrial genome sequences showed that S. japonicum radiated from the middle and lower reaches of the Yangtze River to the mountainous areas of China, Japan and Southeast Asia. In addition, the parasite experienced two population expansions during the Neolithic agriculture era, coinciding with human migration and population growth. The data indicate that the advent of rice planting likely played a key role in the spread of schistosomiasis in Asia. Moreover, the presence of different subspecies of Oncomelania hupensis intermediate host snails in different localities in Asia allowed S. japonicum to survive in new rice-planting areas, and concurrently drove the intraspecies divergence of the parasite. PMID:26686813

  19. Co-dispersal of the blood fluke Schistosoma japonicum and Homo sapiens in the Neolithic Age.

    PubMed

    Yin, Mingbo; Zheng, Hong-Xiang; Su, Jing; Feng, Zheng; McManus, Donald P; Zhou, Xiao-Nong; Jin, Li; Hu, Wei

    2015-01-01

    The global spread of human infectious diseases is of considerable public health and biomedical interest. Little is known about the relationship between the distribution of ancient parasites and that of their human hosts. Schistosoma japonicum is one of the three major species of schistosome blood flukes causing the disease of schistosomiasis in humans. The parasite is prevalent in East and Southeast Asia, including the People's Republic of China, the Philippines and Indonesia. We studied the co-expansion of S. japonicum and its human definitive host. Phylogenetic reconstruction based on complete mitochondrial genome sequences showed that S. japonicum radiated from the middle and lower reaches of the Yangtze River to the mountainous areas of China, Japan and Southeast Asia. In addition, the parasite experienced two population expansions during the Neolithic agriculture era, coinciding with human migration and population growth. The data indicate that the advent of rice planting likely played a key role in the spread of schistosomiasis in Asia. Moreover, the presence of different subspecies of Oncomelania hupensis intermediate host snails in different localities in Asia allowed S. japonicum to survive in new rice-planting areas, and concurrently drove the intraspecies divergence of the parasite. PMID:26686813

  20. Lung fluke (Paragonimus africanus) infects Nigerian red-capped mangabeys and causes respiratory disease

    PubMed Central

    Friant, Sagan; Brown, Kelsey; Saari, Mason T.; Segel, Nicholas H.; Slezak, Julia; Goldberg, Tony L.

    2015-01-01

    Eggs of the lung fluke genus Paragonimus were detected in red-capped mangabeys (Cercocebus torquatus) in Nigeria. We assess the role of these primates as potential sylvatic hosts and the clinical effects of the parasite on monkeys. DNA sequenced from eggs in feces were 100% identical in the ITS2 region to Paragonimus africanus sequences from humans in Cameroon. Paragonimus-positive monkeys coughed more than uninfected monkeys. Experimental de-worming led to reduction in parasite intensity and a corresponding reduction of coughing to baseline levels in infected monkeys. This report provides the first evidence of Paragonimus sp. in C. torquatus, of P. africanus in Nigerian wildlife, and the first molecular evidence of the parasite in African wildlife. Coughing, sometimes interpreted as a communication behavior in primates, can actually indicate infection with lung parasites. Observations of coughing in primates may, in turn, provide a useful mechanism for surveillance of Paragonimus spp, which are re-emerging human pathogens, in wildlife reservoirs. PMID:26543803

  1. Sequencing and characterization of the complete mitochondrial genome from the pancreatic fluke Eurytrema pancreaticum (Trematoda: Dicrocoeliidae).

    PubMed

    Chang, Qiao-Cheng; Liu, Guo-Hua; Gao, Jun-Feng; Zheng, Xu; Zhang, Yan; Duan, Hong; Yue, Dong-Mei; Fu, Xue; Su, Xin; Gao, Yuan; Wang, Chun-Ren

    2016-01-15

    The trematode Eurytrema pancreaticum is a parasite of ruminant pancreatic and bile ducts, and also occasionally infects humans, causing eurytremiasis. In spite of it being a common fluke of cattle and sheep in endemic regions, little is known about the genomic resources of the parasite. We sequenced the complete mitochondrial (mt) genome of E. pancreaticum. It is 15,031 bp in size, and encodes 36 genes: 12 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes. The E. pancreaticum mt gene order is the same as that of Dicrocoelium chinensis and Dicrocoelium dendriticum, and all genes are transcribed in the same direction. Phylogenetic analysis based on the concatenated amino acid sequences of 12 protein-coding genes by Bayesian inference shows that E. pancreaticum is closely related to D. chinensis and other members of the family Dicrocoeliidae with strong posterior probability support. The E. pancreaticum mt genome should prove to be a useful resource for comparative mt genomic studies of digenetic trematodes, and will provide a rich source of DNA markers for studies into the systematics, epidemiology, and population genetics of this parasite and other digenean trematodes. PMID:26434796

  2. Heterophysiasis, an intestinal fluke infection of man and vertebrates transmitted by euryhaline gastropods and fish

    NASA Astrophysics Data System (ADS)

    Taraschewski, H.

    1984-03-01

    Heterophyes heterophyes, agent of human heterophyiasis in the Near East, is transmitted in marine lagoons and saline inland waters, where the euryhaline intermediate hosts are abundant. In Egypt, mullets, the predominant second intermediate hosts, are customarily consumed raw; thus man becomes infected easily. Symptoms of human infections are usually considered mild. Mullets do not seem to be affected by the metacercariae encysted in the muscles, whereas the growth of the snail host Pirenella conica was found to be enhanced due to the infestation by the trematodes. In laboratory experiments, the flukes were found to be well developed in dogs, foxes and cats, but failed to reach sexual maturity in several other potentially piscivorous mammals and birds. In nature, dogs probably serve as the major reservoir hosts. Heterophyiasis is most prevalent in the Nile Delta, a huge brackish water area which is densely populated by humans and, consequently, also by dogs and cats. In the Far East, besides Heterophyes nocens, several other heterophysids with marine or fresh-water life-cycles are known to infect humans.

  3. Sequence Analysis and Molecular Characterization of Clonorchis sinensis Hexokinase, an Unusual Trimeric 50-kDa Glucose-6-Phosphate-Sensitive Allosteric Enzyme

    PubMed Central

    Chen, Tingjin; Ning, Dan; Sun, Hengchang; Li, Ran; Shang, Mei; Li, Xuerong; Wang, Xiaoyun; Chen, Wenjun; Liang, Chi; Li, Wenfang; Mao, Qiang; Li, Ye; Deng, Chuanhuan; Wang, Lexun; Wu, Zhongdao; Huang, Yan; Xu, Jin; Yu, Xinbing

    2014-01-01

    Clonorchiasis, which is induced by the infection of Clonorchis sinensis (C. sinensis), is highly associated with cholangiocarcinoma. Because the available examination, treatment and interrupting transmission provide limited opportunities to prevent infection, it is urgent to develop integrated strategies to prevent and control clonorchiasis. Glycolytic enzymes are crucial molecules for trematode survival and have been targeted for drug development. Hexokinase of C. sinensis (CsHK), the first key regulatory enzyme of the glycolytic pathway, was characterized in this study. The calculated molecular mass (Mr) of CsHK was 50.0 kDa. The obtained recombinant CsHK (rCsHK) was a homotrimer with an Mr of approximately 164 kDa, as determined using native PAGE and gel filtration. The highest activity was obtained with 50 mM glycine-NaOH at pH 10 and 100 mM Tris-HCl at pH 8.5 and 10. The kinetics of rCsHK has a moderate thermal stability. Compared to that of the corresponding negative control, the enzymatic activity was significantly inhibited by praziquantel (PZQ) and anti-rCsHK serum. rCsHK was homotropically and allosterically activated by its substrates, including glucose, mannose, fructose, and ATP. ADP exhibited mixed allosteric effect on rCsHK with respect to ATP, while inorganic pyrophosphate (PPi) displayed net allosteric activation with various allosteric systems. Fructose behaved as a dose-dependent V activator with the substrate glucose. Glucose-6-phosphate (G6P) displayed net allosteric inhibition on rCsHK with respect to ATP or glucose with various allosteric systems in a dose-independent manner. There were differences in both mRNA and protein levels of CsHK among the life stages of adult worm, metacercaria, excysted metacercaria and egg of C. sinensis, suggesting different energy requirements during different development stages. Our study furthers the understanding of the biological functions of CsHK and supports the need to screen for small molecule inhibitors of CsHK to interfere with glycolysis in C. sinensis. PMID:25232723

  4. Liver Cancer

    MedlinePlus

    ... alcohol use Having cirrhosis, or scarring of the liver Having hemochromatosis, an iron storage disease Obesity and diabetes Symptoms can include a lump or pain on the right side of your abdomen and yellowing of the skin. ... that examine the liver and the blood to diagnose liver cancer. Treatment ...

  5. Liver transplantation☆

    PubMed Central

    Rossi, M.; Mennini, G.; Lai, Q.; Ginanni Corradini, S.; Drudi, F.M.; Pugliese, F.; Berloco, P.B.

    2007-01-01

    Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease. The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza). The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center. PMID:23396075

  6. Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

    PubMed Central

    Fajtová, Pavla; Štefanić, Saša; Hradilek, Martin; Dvořák, Jan; Vondrášek, Jiří; Jílková, Adéla; Ulrychová, Lenka; McKerrow, James H.; Caffrey, Conor R.; Mareš, Michael; Horn, Martin

    2015-01-01

    Background Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is a need to identify new targets for chemotherapeutic interventions. Our research is focused on Schistosoma mansoni prolyl oligopeptidase (SmPOP) from the serine peptidase family S9, which has not been investigated in detail in trematodes. Methodology/Principal Findings We demonstrate that SmPOP is expressed in adult worms and schistosomula in an enzymatically active form. By immunofluorescence microscopy, SmPOP is localized in the tegument and parenchyma of both developmental stages. Recombinant SmPOP was produced in Escherichia coli and its active site specificity investigated using synthetic substrate and inhibitor libraries, and by homology modeling. SmPOP is a true oligopeptidase that hydrolyzes peptide (but not protein) substrates with a strict specificity for Pro at P1. The inhibition profile is analogous to those for mammalian POPs. Both the recombinant enzyme and live worms cleave host vasoregulatory, proline-containing hormones such as angiotensin I and bradykinin. Finally, we designed nanomolar inhibitors of SmPOP that induce deleterious phenotypes in cultured schistosomes. Conclusions/Significance We provide the first localization and functional analysis of SmPOP together with chemical tools for measuring its activity. We briefly discuss the notion that SmPOP, operating at the host-parasite interface to cleave host bioactive peptides, may contribute to the survival of the parasite. If substantiated, SmPOP could be a new target for the development of anti-schistosomal drugs. PMID:26039195

  7. Tracking the fate of iron in early development of human blood flukes.

    PubMed

    Jones, Malcolm K; McManus, Donald P; Sivadorai, Padma; Glanfield, Amber; Moertel, Luke; Belli, Sabina I; Gobert, Geoffrey N

    2007-01-01

    Iron (Fe) is an important trace element found in nearly all organisms, and is used as a cofactor in many biological reactions. One role for Fe in some invertebrates is in stabilization of extracellular matrices. The human blood fluke, Schistosoma japonicum, is responsible for significant human disease in developing and tropical nations. Disease in humans arises from host immunological reaction to parasite eggs that lodge in tissues. Schistosomes require Fe for development in their hosts, and store abundant Fe in vitelline (eggshell-forming) cells of the female system. The understanding of Fe metabolism and functionality are aspects of its biology that may be exploited in future therapeutics. The biology of Fe stores in vitelline cells of S. japonicum was investigated to illuminate possible functions of this element in early development of these parasites. Vitelline Fe is stored in yolk ferritin that is upregulated in females and is also expressed at low levels in egg-stages and adult males. Laser microdissection microscopy, coupled with reverse transcriptase- and real time-PCR amplification of schistosome ferritin sequences, confirmed that the vitelline cells are the likely progenitor cells of yolk ferritin. Assessment of Fe concentrations in whole male and whole female adult worms, eggs and purified eggshells by colorimetric assays and mass spectroscopy demonstrated higher levels of Fe in the female parasite, but also high levels of the element in whole parasite eggs and purified eggshell. Qualitative energy dispersive spectroscopy of purified eggshells, revealed that Fe is abundant in the eggshell, the matrix of which is composed of heavily cross-linked eggshell precursor proteins. Thus, vitelline stores of Fe are implicated in eggshell cross-linking in platyhelminths. These observations emphasise the importance of Fe in schistosome metabolism and egg formation and suggest new avenues for disruption of egg formation in these pathogenic parasites. PMID:17556009

  8. Infection status of estuarine fish and oysters with intestinal fluke metacercariae in Muan-gun, Jeollanam-do, Korea.

    PubMed

    Cho, Shin-Hyeong; Kim, In-Sang; Hwang, Eun-Jung; Kim, Tong-Soo; Na, Byoung-Kuk; Sohn, Woon-Mok

    2012-09-01

    The source of human infection with intestinal flukes was surveyed in estuarine fishes, including the dotted gizzard shad, common sea bass, common blackish goby, redlip mullet, black sea bream, and oyster collected from Muan-gun, Jeollanam-do, Korea during August and September 2007. Collected fishes and oysters were artificially digested in pepsin-HCl solution and examined under a stereomicroscope. In 36 shads (Konosirus punctatus) and 20 basses (Lateolabrax japonicus) examined, Heterophyopsis continua metacercariae were found in 58.3% and 100%, and their average numbers were 12.0 and 6.3 per infected fish, respectively. In 34 gobies (Acanthogobius flavimanus) examined, metacercariae of H. continua were detected in 79.4%, Stictodora lari in 97.1%, and Acanthotrema felis in 92.1%, and their average numbers were 45.8, 189.3, and 235.3 per infected fish, respectively. In 37 redlip mullets (Chelon haematocheilus), Heterophyes nocens metacercariae were found in 56.8%, Pygidiopsis summa in 94.6%, and Stictodora fuscata in 45.9%, and the average metacercarial densities were 17.4, 31.3, and 35.1 per infected fish, respectively. In 30 black sea breams (Acanthopagrus schlegeli) and 45 oysters (Crassostrea gigas) examined, no metacercariae were detected. From the above results, it has been confirmed that the dotted gizzard shad, common sea bass, common blackish goby, and redlip mullet from Muan-gun, Jeollanam-do, Korea are infected with the metacercariae of heterophyid flukes. PMID:22949748

  9. MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

    PubMed

    Zhu, Lihui; Zhao, Jiangping; Wang, Jianbin; Hu, Chao; Peng, Jinbiao; Luo, Rong; Zhou, Chunjing; Liu, Juntao; Lin, Jiaojiao; Jin, Youxin; Davis, Richard E; Cheng, Guofeng

    2016-02-01

    Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production. PMID:26871705

  10. MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum

    PubMed Central

    Hu, Chao; Peng, Jinbiao; Luo, Rong; Zhou, Chunjing; Liu, Juntao; Lin, Jiaojiao; Jin, Youxin; Davis, Richard E.; Cheng, Guofeng

    2016-01-01

    Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production. PMID:26871705

  11. Liver spots

    MedlinePlus

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ...

  12. SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni

    PubMed Central

    Dvořák, Jan; Mashiyama, Susan T.; Sajid, Mohammed; Braschi, Simon; Delcroix, Melaine; Schneider, Eric L.; McKerrow, Wilson H.; Bahgat, Mahmoud; Hansell, Elizabeth; Babbitt, Patricia C.; Craik, Charles S.; McKerrow, James H.; Caffrey, Conor R.

    2009-01-01

    Background Blood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide. Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases) facilitates hydrolysis of host hemoglobin and serum proteins. Methodology/Principal Findings We identified a new cathepsin L termed SmCL3 using PCR strategies based on S. mansoni EST sequence data. An ortholog is present in Schistosoma japonicum. SmCL3 was heterologously expressed as an active enzyme in the yeast, Pichia pastoris. Recombinant SmCL3 has a broad pH activity range against peptidyl substrates and is inhibited by Clan CA protease inhibitors. Consistent with a function in degrading host proteins, SmCL3 hydrolyzes serum albumin and hemoglobin, is localized to the adult gastrodermis, and is expressed mainly in those life stages infecting the mammalian host. The predominant form of SmCL3 in the parasite exists as a zymogen, which is unusual for proteases. This zymogen includes an unusually long prodomain with alpha helical secondary structure motifs. The striking specificity of SmCL3 for amino acids with large aromatic side chains (Trp and Tyr) at the P2 substrate position, as determined with positional scanning-synthetic combinatorial library, is consistent with a molecular model that shows a large and deep S2 pocket. A sequence similarity network (SSN) view clusters SmCL3 and other cathepsins L in accordance with previous large-scale phylogenetic analyses that identify six super kingdoms. Conclusions/Significance SmCL3 is a gut-associated cathepsin L that may contribute to the network of proteases involved in degrading host blood proteins as nutrients. Furthermore, this enzyme exhibits some unusual sequence and biophysical features that may result in additional functions. The visualization of network inter-relationships among cathepsins L suggests that these enzymes are suitable ‘marker sequences’ for inclusion in future phylogenetic analyses. PMID:19488406

  13. The effectiveness of repeated tank treatments of copper sulfate and formalin on gill flukes and Ich in naturally infested white bass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ectoparasites infesting the gills of juvenile fish reared in tanks can cause serious fish losses. Multiple treatments of formalin and copper sulfate (CuSO4) were evaluated for effectiveness against a natural infestation of gill flukes Onchocleidus mimus (Monogenoidea: Ancyrocephalidae) and Ichthyop...

  14. Liver bioengineering

    PubMed Central

    Caralt, Mireia; Velasco, Enrique; Lanas, Angel; Baptista, Pedro M

    2014-01-01

    Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization1–3. Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc)4. Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications. PMID:25102189

  15. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other. PMID:17559071

  16. Liver Transplant

    MedlinePlus

    ... are the body rejecting the liver and infections. Rejection occurs when the body’s immune system attacks an object it does not recognize. To prevent rejection, transplant patients are given medicines to weaken the ...

  17. Liver Panel

    MedlinePlus

    ... may potentially damage the liver Those who are alcoholics or heavy drinkers Those who have a history ... persistently increased Normal to slightly increased Normal Normal Alcoholic Hepatitis Normal or increased AST is moderately increased, ...

  18. Liver cirrhosis.

    PubMed Central

    Williams, E. J.; Iredale, J. P.

    1998-01-01

    Liver fibrosis and its related complications continue to represent a significant worldwide healthcare burden. Over the past decade there has been considerable improvement in our understanding of the cellular mechanisms and pathophysiology underlying hepatic fibrosis. This greater insight into the relevant basic sciences may lead to the development of novel treatment strategies designed to block the fibrogenic cascade or even enhance matrix degradation. In addition, there have been significant advances in the management of the complications of cirrhosis, with specific treatments now available for some conditions. Perhaps most notably, liver transplantation is now a highly successful treatment for end-stage liver disease and should be considered in all patients with chronic liver disease. PMID:9683971

  19. Liver transplant

    MedlinePlus

    ... disorders of copper or iron ( Wilson's disease and hemochromatosis ) Liver transplant surgery is often not recommended for ... rest of their lives. This is called immunosuppressive therapy. Although the treatment helps prevent organ rejection, it ...

  20. The liver

    PubMed Central

    Fam, Barbara C.; Joannides, Christos N.; Andrikopoulos, Sofianos

    2012-01-01

    Liver fructose-1,6-bisphosphatase (FBPase) is a regulatory enzyme in gluconeogenesis that is elevated by obesity and dietary fat intake. Whether FBPase functions only in glucose metabolism or has other metabolic roles is currently unclear. In our recently published study, we examined the importance of liver FBPase in body weight regulation by performing a series of comprehensive physiological and biochemical assessments of energy balance and specific intervention studies in our transgenic mouse line that overexpresses FBPase specifically in the liver. Compared with negative littermates, these FBPase transgenic mice weighed 10% less, had 50% less adiposity, ate 15% less food but did not have altered energy expenditure. Increased circulating leptin and cholecystokinin levels, elevated fatty acid oxidation and reduced appetite stimulating neuropeptides, neuropeptide Y (NPY) and agouti-related peptide (AGRP), underpinned this phenotype. Blocking the action of FBPase returned food intake and body weight to those of the negative littermates. Our study is the first to identify liver FBPase as a previously unknown regulator of appetite and adiposity. Importantly, this work recognizes the liver as an important organ in appetite and body weight regulation. This commentary will provide further insight and expand on this novel concept that the liver does in fact play an important role in adiposity. PMID:23700543

  1. Evolutionary avenues for, and constraints on, the transmission of frog lung flukes (Haematoloechus spp.) in dragonfly second intermediate hosts.

    PubMed

    Bolek, Matthew G; Janovy, John

    2007-06-01

    Metacercariae survival patterns and their distribution in second intermediate odonate hosts were examined for 4 species of frog lung flukes. Surveys of aquatic larvae and recently emerged teneral dragonflies and damselflies indicated that prevalence and mean abundance of Haematoloechus spp. metacercariae were significantly lower in teneral dragonflies than larval dragonflies, while there was no significant difference in prevalence or mean abundance of Haematoloechus spp. metacercariae among larval and teneral damselflies. Experimental infections of dragonflies indicated that metacercariae of Haematoloechus coloradensis and Haematoloechus complexus were located in the head, thorax, and branchial basket of dragonflies, whereas metacercariae of Haematoloechus longiplexus and Haematoloechus parviplexus were restricted to the branchial basket of these hosts. Metacercariae of H. coloradensis, H. complexus, and H. longiplexus infected the head, thorax, and abdomen of damselflies, but these insects were resistant to infection with H. parviplexus. Subsequent metamorphosis experiments on experimentally infected dragonflies indicated that most metacercariae of H. longiplexus were lost from the branchial basket during metamorphosis, but most metacercariae of H. coloradensis, H. complexus, and H. parviplexus survived dragonfly metamorphosis. These observations suggest that the observed ecological host specificity of H. longiplexus in semiterrestrial leopard frogs may be due to few metacercariae of H. longiplexus reaching these frogs in a terrestrial environment. Because of the uncertain validity of Haematoloechus varioplexus as a distinct species from its synonym H. parviplexus, their morphological characters were reevaluated. The morphological data on H. varioplexus and H. parviplexus indicate that they differ in their acetabulum length and width, ovary shape, testes length, and egg length and width. Experimental infections of plains leopard frogs, northern leopard frogs, and bullfrogs with worms from bullfrogs indicate that the synonymy of H. parviplexus with H. varioplexus is not warranted, and that these flukes are distinct species, i.e., H. parviplexus in bullfrogs and H. varioplexus in plains leopard frogs and northern leopard frogs. PMID:17626352

  2. Impaired antioxidant enzyme activity and increased DNA repair enzyme expression in hamster liver tissues related to cholangiocarcinoma development.

    PubMed

    Loilome, Watcharin; Kadsanit, Sasithorn; Namwat, Nisana; Techasen, Anchalee; Puapairoj, Anucha; Dechakhamphu, Ananya; Pinitsoontorn, Chadamas; Yongvanit, Puangrat

    2012-01-01

    A possible mechanism of liver fluke (Opisthorchis viverrini; Ov) -associated cholangiocarcinoma (CCA) genesis may be imbalance in responses of antioxidant enzymes and/or DNA repair enzymes which are the consequence of oxidative/nitrative stress, arising from inflammatory processes. This study aimed to investigate changes in the expression patterns of antioxidant enzymes, including superoxide dismutase 2 (SOD2) and catalase (CAT), as well as their activities in Ov-associated hamster CCA tissues. Expression of DNA repair enzymes including apurinic endonuclease (APE) and DNA polymerase beta (DNA pol β) was also investigated. Our results showed that SOD2 and CAT levels were increased in CCA-induced liver hamster tissues at every time point during cholangiocarcinogenesis. However, once tumors were well established, activities of both enzymes were significantly decreased. Expression of APE and DNA pol β was increased in the acute phase of Ov infection and this persisted until tumors developed. These findings suggest that a reduction in antioxidant enzymes and an increase in DNA repair enzymes may contribute to DNA translesion-mediated CCA in liver fluke-associated cholangiocarcinogenesis in the hamster model. PMID:23480773

  3. Whole transcriptome profiling of adult and infective stages of the trematode Opisthorchis felineus.

    PubMed

    Pomaznoy, Mikhail Yu; Logacheva, Maria D; Young, Neil D; Penin, Aleksey A; Ershov, Nikita I; Katokhin, Alexey V; Mordvinov, Viatcheslav A

    2016-02-01

    Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a causative agent of the infection called opisthorchiasis or liver fluke infection. Being a close relative of Opisthorchis viverrini and Clonorchis sinensis (oriental liver flukes) it is encountered in northern Eurasia, especially in Russia, Kazakhstan, Belarus, Ukraine, and Baltic countries. Whole genome data for oriental liver flukes revealed their adaptations for life in the bile duct but our knowledge of O. felineus is scarce. To address this knowledge gap and uncover evolutionary aspect of the adaptations on the transcriptomic level, we used RNA-sequencing approach to investigate two stages of the parasite residing in different hosts. Bioinformatic analysis revealed specific features affecting various biochemical pathways and gene networks. Namely, we observed the loss of genes involved in polyamine synthesis, methionine salvage and peroxisome biogenesis. Some of the gene families, like MD-2 lipid binding proteins, calmodulins and cathepsins on the contrary have expanded compared to free living eukaryotes. We identified significant differences between the stages in homeodomain-containing genes, G-protein coupled receptors, and neuroactive signaling systems. Granulin-like growth factors specific for O. felineus were also identified. In this work, we provide the first whole transcriptome investigation of this parasite. We also hope that these results will create a background for further molecular research of helminth infections and opisthorchiasis in particular. PMID:26363139

  4. Benign Liver Tumors

    MedlinePlus

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  5. American Liver Foundation

    MedlinePlus

    ... Liver Function Tests Liver Transplant Newborn Jaundice Non-Alcoholic Fatty Liver Disease Primary Biliary Cholangitis (PBC) Primary Sclerosing Cholangitis (PSC) Progression of Liver Disease Reye Syndrome Type I Glycogen Storage Disease Wilson Disease Find Your ...

  6. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  7. Liver disease - resources

    MedlinePlus

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  8. Population dynamics and host reactions in young foxes following experimental infection with the minute intestinal fluke, Haplorchis pumilio

    PubMed Central

    2013-01-01

    Background Infections with fish-borne zoonotic trematodes (FZT) including the minute intestinal fluke, Haplorchis pumilio, are highly prevalent in Southeast Asia. However, little is known about the infection dynamics and clinical symptoms in the final hosts which include a range of animal species and man. We aimed to generate such information using an experimental model with H. pumilio in foxes. Method Eight commercially bred foxes were each orally infected with 2000 H. pumilio metacercariae. Another three foxes served as uninfected controls. Faecal examination for eggs was performed twice weekly. The body weight was measured, standard haematological and biochemical analysis were performed regularly. All foxes were euthanized at day 56 post infection (p.i.). Adult worms were quantified and location in the small intestine noted. Results Anorexia was observed in all infected foxes starting day 12 p.i. and lasting for approximately a week. A weight loss was noticed in the infected group in weeks 3–6 p.i. Five of eight infected foxes excreted H. pumilio eggs day 9 p.i. onwards, the remaining three started on day 13 p.i. Mean (± SD) faecal egg counts showed an initial peak at day 16–20 with a maximum of 1443 ± 1176 eggs per gram of faeces (epg), where after a stable egg output around 4–500 epg was seen. Worm burdens ranged between 116–2070 adult flukes with a mean (± SD) worm recovery of 948 ± 666. The majority of worms were found in the lower part of the jejunum. Total white blood cell and lymphocyte counts were significant lower in the infected group from first week p.i. onwards and throughout the study period. A significantly lower level of eosinophils was found in week 2 p.i. and transient anaemia was seen in week 2 and 4 p.i. Conclusion This study showed a short prepatency period, an initial peak in egg excretion, establishment of infection in all animals with predilection site in the lower jejunum and a marked but transient clinical effect of the infection. The findings on egg output and prepatency should be taken into consideration when control programs targeting dogs and other reservoir hosts are to be established. PMID:23289937

  9. Haplorchis taichui, Witenberg, 1930: Development of a HAT-RAPD marker for the detection of minute intestinal fluke infection.

    PubMed

    Wongsawad, Chalobol; Wongsawad, Pheravut; Chai, Jong Yil; Anuntalabhochai, Somboon

    2009-10-01

    Specific primers to determine the presence of an intestinal fluke, Haplorchis taichui, were investigated using the high annealing temperature random amplified polymorphic DNA (HAT-RAPD) PCR, and 18 arbitrary primers (Operon Technologies), to generate different polymorphic DNA profiles. Thirteen kinds of parasites were used to compare fingerprints. A 256bp HAT-RAPD marker, generated from the OPP-11 primer, was found to be H. taichui-specific, and this marker was cloned, transformed, and sequenced. From the sequence data, a pair of primers were designed with Genetyx-MAC ver.11 and indicated as: Hap-t F 5'-GGC CAA CGC AAT CGT CAT CC-3' and Hap-t R 5'-GCG TCG GGT TTC AGA CAT GG-3'. These specific primers were tested for efficacy and specificity by amplifying them with all 13 parasites DNAs in PCR reaction. A 256bp amplicon was generated, which was shown to have a positive result, only for H. taichui DNA. It revealed no cross-reaction with any of the other tested parasite species. The minimum DNA template, needed for detection by PCR, was 0.1picogram (pg). The successful development of H. taichui-specific primers is expected to be beneficial for epidemiological studies and for prevention and control of these parasitic infections. PMID:19563805

  10. Correlation of humoral immune response in southern bluefin tuna, T. maccoyii, with infection stage of the blood fluke, Cardicola forsteri.

    PubMed

    Kirchhoff, Nicole T; Leef, Melanie J; Valdenegro, Victoria; Hayward, Craig J; Nowak, Barbara F

    2012-01-01

    The blood fluke, Cardicola forsteri, is a prevalent infection in ranched southern bluefin tuna. This project aimed to define the timing and intensity of the various developmental stages of C. forsteri within southern bluefin tuna as well as to relate infection to host pathology and immune response. Archival samples from several cohorts of T. maccoyii sampled from 2008 to 2010 were used in this study. The prevalence and intensity of C. forsteri infection was described using heart flushes and histological examination. Humoral immune response, i.e. C. forsteri specific antibody, lysozyme activity, and alternative complement activity, was also described. Based on the validated and detailed C. forsteri infection timeline, relationships between infection events, physiological response, and diagnosis were proposed. Immune response developed concurrently with C. forsteri infection, with the majority of physiological response coinciding with commencing egg production. Further research is needed to confirm the origin of C. forsteri antigen which is responsible for immune response development and how T. maccoyii immune response works against infection. To aide this research, further diagnostic methods for confirmation of infection need to be developed. PMID:23029217

  11. Bilirubin binding with liver cystatin induced structural and functional changes.

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

    Cysteine proteinases and their inhibitors play a significant role in the proteolytic environment of the cells. Inhibitors of cysteine proteinases regulate the activity of these enzymes helping in checking the degdration activity of cathepsins. The bilirubin secreated by liver cells can bind to cystatin present in the liver resulting in its functional inactivation, which may further lead to the increase in cathepsins level causing liver cirrhosis. In case of some pathophysiological conditions excess bilirubin gets accumulated e.g. in presence of Fasciola hepatica (liver fluke) in mammals and humans, leading to liver cirrhosis and possibly jaundice or normal blockade of bile duct causing increased level of bilirubin in blood. Protease-cystatin imbalance causes disease progression. In the present study, Bilirubin (BR) and liver cystatin interaction was studied to explore the cystatin inactivation and structural alteration. The binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of BR with buffalo liver cystatin (BLC). Stern-Volmer analysis of BR-BLC system indicates the presence of static component in the quenching mechanism and the number of binding sites to be close to 1. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. FTIR analysis of BR-Cystatin complex revealed change in the secondary structure due to perturbation in the microenvironment further confirmed by the decreased caseinolytic activity of BLC against papain. Fluorescence measurements also revealed quenching of fluorescence and shift in peak at different time intervals and at varying pH values. Photo-illumination of BR-cystatin complex causes change in the surrounding environment of liver cystatin as indicated by red-shift. The binding constant for BR-BLC complex was found to be 9.279 × 10(4) M(-1). The cystatin binding with bilirubin has a significant biophysical and pathophysiological significance, hence our effort to study the same. PMID:24711081

  12. Sj-FABPc fatty-acid-binding protein of the human blood fluke Schistosoma japonicum: structural and functional characterization and unusual solvent exposure of a portal-proximal tryptophan residue.

    PubMed Central

    Kennedy, M W; Scott, J C; Lo, S; Beauchamp, J; McManus, D P

    2000-01-01

    Sj-FABPc of the blood fluke of humans, Schistosoma japonicum, is a member of the FABP/P2/CRBP/CRABP family of beta-barrel cytosolic fatty-acid-binding and retinoid-binding proteins. Sj-FABPc has at least eight different variants encoded by a single-copy polymorphic gene. In fluorescence-based assays, recombinant Sj-FABPc was found to bind 11-(dansylamino)undecanoic acid (DAUDA), inducing a shift in peak fluorescence emission from 543 to 493 nm. A similar spectral change was observed in dansyl-amino-octanoic acid (in which the dansyl fluorophore is attached at the alpha-carbon rather than the omega-carbon of DAUDA), indicating that the ligand enters entirely into the binding site. Sj-FABPc also bound the naturally fluorescent cis-parinaric acid, as well as oleic acid and arachidonic acid, by competition, but not all-trans-retinol. Dissociation constants were, for cis-parinaric acid, K(d)=2.5+/-0.1 microM (mean+/-S.E.M.) and an apparent stoichiometry consistent with one binding site per molecule of Sj-FABPc and, for oleic acid, K(i) approximately 80 nM. A deletion mutant from which alpha-II was absent failed to bind ligand. Sj-FABPc modelled well to known structures of the protein family; an unusually solvent-exposed Trp side chain was evident adjacent to the presumptive portal through which ligand is thought to enter and leave. Intrinsic fluorescence analyses of Sj-FABPc and of the deletion mutant (from which Trp-27 is absent) confirmed the unusual disposition of this side chain. Virtually all members of the FABP/P2/CRBP/CRABP protein family have prominent hydrophobic side chains in this position, with the exception of liver FABP and ileal FABP, which instead have charged side chains. Liver FABP is known to be distinct from other members of the protein family in that it does not seem to contact membranes to collect and deposit its ligand. It is therefore postulated that the unusually positioned apolar side chains in Sj-FABPc and others in the family are important in interactions with membranes or other cellular components. PMID:10861250

  13. Liver Function Tests

    MedlinePlus

    ... proteins found in the blood are globulins and albumin. Globulin is a protein made in your liver ... a sign of liver damage or other conditions. Albumin is another protein made in your liver. An ...

  14. Liver Function Tests

    MedlinePlus

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  15. Differences in the compatibility of infection between the liver flukes Fascioloides magna and Fasciola hepatica in a Colombian population of the snail Galba sp.

    PubMed

    Dreyfuss, G; Correa, A C; Djuikwo-Teukeng, F F; Novobilský, A; Höglund, J; Pankrác, J; Kašný, M; Vignoles, P; Hurtrez-Boussès, S; Pointier, J P; Rondelaud, D

    2015-11-01

    Experimental infections of Galba sp. (origin, Colombia) with allopatric isolates of Fasciola hepatica from France or Fascioloides magna from the Czech Republic were carried out during five successive snail generations to determine if this lymnaeid might sustain complete larval development of either parasite. In snails exposed to F. hepatica, 7 of 400 snails harboured several rediae and only two snails contained a small number of free cercariae on day 50 post-exposure. In contrast, the intensity of F. magna infection in Galba sp. progressively increased from the F1 to F5 generations. Spontaneous cercarial shedding of F. magna occurred in 7 of 100 Galba sp. belonging to the F5 generation and the number of shed cercariae did not differ significantly from that noted in control Galba truncatula of French origin. Galba sp. from Colombia can be added to the list of potential intermediate hosts for F. magna. PMID:25000491

  16. The Carcinogenic Liver Fluke Opisthorchis viverrini among Rural Community People in Northeast Thailand: a Cross- Sectional Descriptive Study using Multistage Sampling Technique.

    PubMed

    Kaewpitoon, Soraya J; Kaewpitoon, Natthawut; Rujirakul, Ratana; Ueng-Arporn, Naporn; Matrakool, Likit; Tongtawee, Taweesak

    2015-01-01

    Opisthorchis viverrini infection is a serious public health problem in Southeast Asia especially in the northeast and north of Thailand. Therefore, a cross-sectional survey using multistage sampling was conducted from the rural communities of Surin province, Thailand, during September 2013 to July 2014. O. viverrini infection was determined using Kato's thick smear technique. Socio-demographic, information resources, and history data were collected using predesigned semi-structured questionnaires. A total of 510 participants completed interviews and had stools collected. Some 32 (6.47%) participants were infected with O. viverrini. The rate was slightly higher in males (6.61%) than females (6.32%). High frequencies were found in the age groups 61-70 (19.4%) and 71-80 years (19.4%), those involved in agriculture (10.5%), and in primary school (10.3%). The distribution of high infection was found in Tha Tum (16.7%) and Sankha district (16.7%), followed by Samrong Thap (13.3%), Si Narong (13.33%), and Buachet district (13.33%). Chi-square testing indicated that age (61-70 and 71-80 year old), education (primary school) and occupation (agriculture), were significantly associated with O. viverrini infection (p-value<0.05). Of 72.6% participants who had past histories with stool examination, 17.0% of them had been infected with O. viverrini and 43.2% treated with praziquantel. This finding confirmed that O. viverrini is still a problem in Surin province, Thailand, and therefore, interventions are urgently required for mass treatment and health education implementation. PMID:26625801

  17. Amplification of chromosome 21q22.3 harboring trefoil factor family genes in liver fluke related cholangiocarcinoma is associated with poor prognosis

    PubMed Central

    Muenphon, Kanuengnuch; Limpaiboon, Temduang; Jearanaikoon, Patcharee; Pairojkul, Chawalit; Sripa, Banchob; Bhudhisawasdi, Vajarabhongsa

    2006-01-01

    AIM: To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes (TFF) in cholangiocarcinoma (CCA) patients and analyze the correlation between allelic imbalances and clinicopathological parameters. METHODS: Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes (TFF1, TFF2, and TFF3) using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by χ2-tests. Kaplan-Meier method was used to analyze survival. RESULTS: The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis (mean: 51.7 wk vs 124.82 wk, P = 0.012). Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis. CONCLUSION: D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients. PMID:16830362

  18. Natural prevalence in Cuban populations of the lymnaeid snail Galba cubensis infected with the liver fluke Fasciola hepatica: small values do matter.

    PubMed

    Vázquez, Antonio A; Sánchez, Jorge; Alba, Annia; Pointier, Jean-Pierre; Hurtrez-Boussès, Sylvie

    2015-11-01

    Natural infections of lymnaeid snails by Fasciola hepatica are of primary importance to study transmission. Also, infected snails in the field can be used to explore the existing compatibility in host-parasite interactions. This paper aimed to describe the infection rate of Galba cubensis populations in fasciolosis transmission areas. Eight sites were sampled in western Cuba and 24 infected snails at six sites were found. The mean prevalence was 2.94% and the maximum value was 11.4%. The intensity of parasite infection was assessed as the number of rediae inside a single snail. High variation within the sites examined was observed, but a maximum of 76 rediae was recovered from one individual. Although the presence of two other trematode families (Schistosomatidae and Paramphistomatidae) was discovered in dissected individuals, no co-infection with F. hepatica was observed. This is the first time a study of natural prevalence of F. hepatica infection is carried out in Cuba, considered a hyper endemic country for bovine fasciolosis. Our results suggest that fasciolosis transmission may occur even when the number of infected snails remains relatively low. PMID:26250985

  19. Alcohol-Related Liver Disease

    MedlinePlus

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  20. Food-Borne Trematodiases

    PubMed Central

    Keiser, Jennifer; Utzinger, Jürg

    2009-01-01

    Summary: An estimated 750 million people are at risk of infections with food-borne trematodes, which comprise liver flukes (Clonorchis sinensis, Fasciola gigantica, Fasciola hepatica, Opisthorchis felineus, and Opisthorchis viverrini), lung flukes (Paragonimus spp.), and intestinal flukes (e.g., Echinostoma spp., Fasciolopsis buski, and the heterophyids). Food-borne trematodiases pose a significant public health and economic problem, yet these diseases are often neglected. In this review, we summarize the taxonomy, morphology, and life cycle of food-borne trematodes. Estimates of the at-risk population and number of infections, geographic distribution, history, and ecological features of the major food-borne trematodes are reviewed. We summarize clinical manifestations, patterns of infection, and current means of diagnosis, treatment, and other control options. The changing epidemiological pattern and the rapid growth of aquaculture and food distribution networks are highlighted, as these developments might be associated with an elevated risk of transmission of food-borne trematodiases. Current research needs are emphasized. PMID:19597009

  1. Characterization of Constituents and Anthelmintic Properties of Hagenia abyssinica

    PubMed Central

    Thomsen, Henrieke; Reider, Katrin; Franke, Katrin; Wessjohann, Ludger A.; Keiser, Jennifer; Dagne, Ermias; Arnold, Norbert

    2012-01-01

    The dried female flowers of Hagenia abyssinica (Bruce) J. F. Gmel. (Rosaceae) are traditionally used as an anthelmintic remedy in Ethiopia and formerly were incorporated into the European Pharmacopoeia. One-, two- and tricyclic phloroglucinol derivatives (kosins) were suggested to be the active principles. However, polar constituents may also contribute to the activity. Therefore, we investigated for the first time the polar constituents. We isolated typical Rosaceae constituents such as quercetin 3-O-β-glucuronide, quercetin 3-O-β-glucoside and rutin. Polar kosin glycosides or derivatives could not be detected. The anthelmintic activity of fractions of different polarity were tested against the blood fluke Schistosoma mansoni, the liver flukes Clonorchis sinensis and Fasciola hepatica and the intestinal fluke Echinostoma caproni. The anthelmintic activity decreased with increasing polarity of the tested fractions. ESI-MS investigations indicated the predominant occurrence of kosins in the active fractions. Using the anthelmintic active extracts of Hagenia abyssinica we developed a simple, inexpensive bioassay against the non-parasitic nematode Caenorhabditis elegans, which can be used as an initial screening procedure for anthelmintic properties of crude extracts of plants or fungi. The anthelmintic activity of test extracts against the model organism was determined in a microtiter plate assay by enumeration of living and dead nematodes under a microscope. PMID:22896828

  2. Role of liver progenitors in liver regeneration

    PubMed Central

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A.

    2015-01-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs. PMID:25713804

  3. Liver xenotransplantation.

    PubMed

    Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

    1993-10-01

    During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure. PMID:25951555

  4. Engineering Liver

    PubMed Central

    Griffith, Linda G.; Wells, Alan; Stolz, Donna Beer

    2014-01-01

    Interest in “engineering liver” arises from multiple communities: therapeutic replacement; mechanistic models of human processes; and drug safety and efficacy studies. An explosion of micro- and nano-fabrication, biomaterials, microfluidic, and other technologies potentially afford unprecedented opportunity to create microphysiological models of human liver, but engineering design principles for how to deploy these tools effectively towards specific applications, including how to define the essential constraints of any given application (including available sources of cells, acceptable cost, and user-friendliness) are still emerging. Arguably less appreciated is the parallel growth in computational systems biology approaches towards these same problems – particularly, in parsing complex disease processes from clinical material, building models of response networks, and in how to interpret the growing compendium of data on drug efficacy and toxicology in patient populations. Here, we provide insight into how the complementary paths of “engineering liver” – experimental and computational – are beginning to interplay towards greater illumination of human disease states and technologies for drug development. PMID:24668880

  5. Liver disease in menopause

    PubMed Central

    Brady, Carla W

    2015-01-01

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure. PMID:26167064

  6. Liver disease in menopause.

    PubMed

    Brady, Carla W

    2015-07-01

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure. PMID:26167064

  7. Discrimination of O. viverrini, C. sinensis, H. pumilio and H. taichui using nuclear DNA-based PCR targeting ribosomal DNA ITS regions.

    PubMed

    Sato, Megumi; Thaenkham, Urusa; Dekumyoy, Paron; Waikagul, Jitra

    2009-01-01

    Small liver and minute intestinal flukes are highly prevalent in Southeast Asia, and in mixed infections, their eggs are difficult to differentiate morphologically in fecal samples. PCR assays targeting the ITS regions in ribosomal DNA were designed to identify and differentiate species. The PCR amplicons of Opisthorchis viverrini, Clonorchis sinensis, Haplorchis pumilio, and Haplorchis taichui were 800, 820, 1250, and 930 bp for the ITS1 region, and 380, 390, 380, and 530 bp for ITS2, respectively. The ITS1-region amplicon sizes successfully differentiated 4 species, while only H. taichui were significantly different from the other 3 species in the ITS2 region. PCR assays were employed for preliminary analysis using fecal samples diagnosed as having "small trematode eggs" by modified thick smear, showing 76.2% sensitivity for ITS1 and 95.2% for ITS2. PMID:18952037

  8. Liver fibrosis markers in alcoholic liver disease.

    PubMed

    Chrostek, Lech; Panasiuk, Anatol

    2014-07-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

  9. Liver fibrosis markers in alcoholic liver disease

    PubMed Central

    Chrostek, Lech; Panasiuk, Anatol

    2014-01-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

  10. Fluke egg characteristics for the diagnosis of human and animal fascioliasis by Fasciola hepatica and F. gigantica.

    PubMed

    Valero, M Adela; Perez-Crespo, Ignacio; Periago, M Victoria; Khoubbane, Messaoud; Mas-Coma, Santiago

    2009-08-01

    In trematodiases, shape and size of the fluke eggs shed with faeces are crucial diagnostic features because of their typically reduced intraspecific variability. In fascioliasis, the usual diagnosis during the biliary stage of infection is based on the classification of eggs found in stools, duodenal contents or bile. The aim of the present study is to validate the identification of Fasciola species based on the shape and size of eggs shed by humans, characterizing their morphometric traits using a computer image analysis system (CIAS). The influence of both the geographical location and of the host (human and livestock) has been analysed. Coprological studies were carried out in fascioliasis human endemic areas, where only F. hepatica is present (the northern Bolivian Altiplano and the Cajamarca valley in Peru), and where F. hepatica and F. gigantica coexist (the Kutaisi region of Georgia, the Nile Delta in Egypt, and the Quy Nhon province in Vietnam). Classically, it is considered that at the abopercular end of the shell of Fasciola eggs there is often a roughened or irregular area. Nevertheless, results show that the frequency of the presence of this feature in F. hepatica is population-dependent, and therefore is not a pathognomonic criterion in diagnosis. The study reveals that eggs shed by humans show morphological traits different from eggs shed by animals. In humans, F. hepatica eggs are bigger and F. gigantica eggs are smaller than reported to date from livestock, and their measurements overlap when compared. The material analysed in this study shows that the size of eggs shed by humans from Georgia and Egypt corresponds to the F. hepatica morph, while the size of eggs shed by humans from Vietnam corresponds to the F. gigantica morph. Measurements of F. hepatica and F. gigantica eggs originating from humans and animals from sympatric areas overlap, and, therefore, they do not allow differential diagnosis when within this overlapping range. In this sense, the new results should aid clinicians since the application of the classic egg size range in human samples may lead to erroneous conclusions. Fasciolid egg size in human stool samples ought to be corrected in books and monographs related to medical parasitology and/or tropical medicine as well as in guides for clinicians and parasitic disease diagnosis analysts. PMID:19375410

  11. Liver progenitor cells-mediated liver regeneration in liver cirrhosis.

    PubMed

    Shang, Haitao; Wang, Zhijun; Song, Yuhu

    2016-05-01

    Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury. In cirrhotic liver where hepatocytes proliferation is compromised, liver progenitor cells (LPCs) are activated and then differentiated into hepatocytes and cholangiocytes, leading to the generation of regenerative nodules and functional restoration. Here, we summarize and discuss recent findings on the mechanisms underlying LPCs-mediated regeneration in liver cirrhosis. Firstly, we provide recent research on the mechanism underlying LPCs activation in severe or chronic liver injury. Secondly, we present new and exciting data on exploring the origin of LPCs, which reveal that the hepatocytes give rise to duct-like progenitors that then differentiate back into hepatocytes in chronic liver injury or liver cirrhosis. Finally, we highlight recent findings from the literature exploring the role of LPCs niche in directing the behavior and fate of LPCs. This remarkable insight into the cellular and molecular mechanisms of LPCs-mediated regeneration in liver cirrhosis will provide a basis for translating this knowledge into clinical application. PMID:26742763

  12. [Anesthesia with liver failure].

    PubMed

    Camboni-Schellenberg, Eva-Lotte; Sinner, Barbara

    2016-01-01

    Liver failure can be categorized into acute liver failure, chronic liver failure and acute decompensation of chronic liver failure, the so-called acute-on-chronic liver failure, the incidence of which has increased over the last few years. Liver failure leads to a variety of pathophysiological changes where the extent is dependent on the nature and duration of the liver disease. This includes restriction of synthesis and metabolism, such as coagulation defects. Especially chronic liver failure is associated with malfunction of extrahepatic organs, such as the cardiovascular system, the respiratory system and the kidneys. In addition to these pathophysiological alterations the Child-Turcotte-Pugh classification (CTP) and the model of end stage liver disease (MELD) are used for perioperative risk stratification. PMID:26727937

  13. Biomarkers for liver fibrosis

    SciTech Connect

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  14. The mitochondrial genome of Paragonimus westermani (Kerbert, 1878), the Indian isolate of the lung fluke representative of the family Paragonimidae (Trematoda)

    PubMed Central

    Biswal, Devendra K.; Chatterjee, Anupam

    2014-01-01

    Among helminth parasites, Paragonimus (zoonotic lung fluke) gains considerable importance from veterinary and medical points of view because of its diversified effect on its host. Nearly fifty species of Paragonimus have been described across the globe. It is estimated that more than 20 million people are infected worldwide and the best known species is Paragonimus westermani, whose type locality is probably India and which infects millions of people in Asia causing disease symptoms that mimic tuberculosis. Human infections occur through eating raw crustaceans containing metacercarie or ingestion of uncooked meat of paratenic hosts such as pigs. Though the fluke is known to parasitize a wide range of mammalian hosts representing as many as eleven families, the status of its prevalence, host range, pathogenic manifestations and its possible survivors in nature from where the human beings contract the infection is not well documented in India. We took advantage of the whole genome sequence data for P. westermani, generated by Next Generation Sequencing, and its comparison with the existing data for the P. westermani for comparative mt DNA phylogenomic analyses. Specific primers were designed for the 12 protein coding genes with the aid of existing P. westermani mtDNA as the reference. The Ion torrent next generation sequencing platform was harnessed to completely sequence the mitochondrial genome, and applied innovative approaches to bioinformatically assemble and annotate it. A strategic PCR primer design utilizing the whole genome sequence data from P. westermani enabled us to design specific primers capable of amplifying all regions of the mitochondrial genome from P. westermani. Assembly of NGS data from libraries enriched in mtDNA sequence by PCR gave rise to a total of 11 contigs spanning the entire 14.7 kb mt DNA sequence of P. westermani available at NCBI. We conducted gap-filling by traditional Sanger sequencing to fill in the gaps. Annotation of non-protein coding genes successfully identified tRNA regions for the 24 tRNAs coded in mtDNA and 12 protein coding genes. Bayesian phylogenetic analyses of the concatenated protein coding genes placed P. westermani within the family Opisthorchida. The complete mtDNA sequence of P. westermani is 15,004 base pairs long; the lung fluke is the major etiological agent of paragonimiasis and the first Indian representative for the family Paragonimidae to be fully sequenced that provides important genetic markers for ecological, population and biogeographical studies and molecular diagnostic of digeneans that cause trematodiases. PMID:25165620

  15. Fatty liver - nonalcoholic

    MedlinePlus

    ... serious form of the disease is called non-alcoholic steatohepatitis (NASH). NASH can cause liver failure. It ... Gastroenterological Association. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American ...

  16. What Is Liver Cancer?

    MedlinePlus

    ... of HCC. Here “liver cancer” is hepatocellular carcinoma. Intrahepatic cholangiocarcinoma (bile duct cancer) About 10% to 20% of cancers that start in the liver are intrahepatic cholangiocarcinomas. These cancers start in the cells that line ...

  17. Hepatic (Liver) Function Panel

    MedlinePlus

    ... by the liver and attached to other chemicals). Albumin and total protein. Protein is needed to build ... so protein levels decrease. Liver function tests measure albumin specifically (the major blood protein produced by the ...

  18. Antioxidants in liver health

    PubMed Central

    Casas-Grajales, Sael; Muriel, Pablo

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734

  19. Liver transplant - series (image)

    MedlinePlus

    Liver failure causes many problems, including malnutrition, problems with blood clotting, bleeding form the gastrointestinal tract, and jaundice. Frequently, patients who undergo liver transplantation are quite ill, and require ...

  20. AN APPROACH TO REVEALING BLOOD FLUKE LIFE CYCLES, TAXONOMY, AND DIVERSITY: PROVISION OF KEY REFERENCE DATA INCLUDING DNA SEQUENCE FROM SINGLE LIFE CYCLE STAGES

    PubMed Central

    Brant, Sara V.; Morgan, Jess A. T.; Mkoji, Gerald M.; Snyder, Scott D.; Rajapakse, R. P. V. Jayanthe; Loker, Eric S.

    2008-01-01

    Revealing diversity among extant blood flukes, and the patterns of relationships among them, has been hindered by the difficulty of determining if specimens described from different life cycle stages, hosts, geographic localities, and times represent the same or different species. Persistent collection of all available life cycle stages and provision of exact collection localities, host identification, reference DNA sequences for the parasite, and voucher specimens eventually will provide the framework needed to piece together individual life cycles and facilitate reconciliation with classical taxonomic descriptions, including those based on single life cycle stages. It also provides a means to document unique or rare species that might only ever be recovered from a single life cycle stage. With an emphasis on the value of new information from field collections of any available life cycle stages, here we provide data for several blood fluke cercariae from freshwater snails from Kenya, Uganda, and Australia. Similar data are provided for adult worms of Macrobilharzia macrobilharzia and miracidia of Bivitellobilharzia nairi. Some schistosome and sanguinicolid cercariae that we recovered have peculiar morphological features, and our phylogenetic analyses (18S and 28S rDNA and mtDNA CO1) suggest that 2 of the new schistosome specimens likely represent previously unknown lineages. Our results also provide new insights into 2 of the 4 remaining schistosome genera yet to be extensively characterized with respect to their position in molecular phylogenies, Macrobilharzia and Bivitellobilharzia. The accessibility of each life cycle stage is likely to vary dramatically from one parasite species to the next, and our examples validate the potential usefulness of information gleaned from even one such stage, whatever it might be. PMID:16629320

  1. Liver Transplantation for Alcoholic Liver Disease.

    PubMed

    Addolorato, Giovanni; Bataller, Ramón; Burra, Patrizia; DiMartini, Andrea; Graziadei, Ivo; Lucey, Michael R; Mathurin, Philippe; OʼGrady, John; Pageaux, Georges; Berenguer, Marina

    2016-05-01

    Alcohol-related liver disease is the second most frequent indication for liver transplantation (LT), yet as many as 90% to 95% of patients with alcohol-related end-stage liver disease are never formally evaluated for LT. Furthermore, despite its significance as a cause of chronic liver disease and indication for LT, it has received little attention in recent years for several reasons, including the good posttransplant short-term results, and the lack of specific "drugs" used for this disease. A writing group, endorsed by the International Liver Transplant Society, was convened to write guidelines on Liver Transplantation for Alcoholic Liver Disease to summarize current knowledge and provide answers to controversial and delicate ethical as well as clinical problems. We report here a short version of the guidelines (long version available at www.ilts.org) with the final recommendations graded for level of evidence. The writing group membership is expected to remain active for 5 years, reviewing the guideline annually, and updating the online version when appropriate. PMID:26985744

  2. Acute liver failure and liver transplantation

    PubMed Central

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2013-01-01

    Summary Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted. PMID:25343108

  3. Nonalcoholic fatty liver disease

    PubMed Central

    Adams, Leon A.; Angulo, Paul; Lindor, Keith D.

    2005-01-01

    NONALCOHOLIC FATTY LIVER DISEASE is emerging as the most common chronic liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. In this article we discuss the etiology, pathogenesis and diagnosis of nonalcoholic fatty liver disease as well as approaches to its management. PMID:15795412

  4. Coffee and Liver Disease.

    PubMed

    Wadhawan, Manav; Anand, Anil C

    2016-03-01

    Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality. PMID:27194895

  5. FXR and liver carcinogenesis

    PubMed Central

    Huang, Xiong-fei; Zhao, Wei-yu; Huang, Wen-dong

    2015-01-01

    Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer. PMID:25500874

  6. Aging and liver disease

    PubMed Central

    Kim, Hee; Kisseleva, Tatiana; Brenner, David A.

    2016-01-01

    Purpose of review Aging is a condition in which a person gradually loses the ability to maintain homeostasis, due to structural alteration or dysfunction. Aging is a major risk factor for most chronic diseases. As the liver has a remarkable ability to regenerate, this review assessed the effect of aging on clinical liver disease with references to preclinical models when relevant to pathogenesis. Recent findings Aging has been shown to not only enhance vulnerability to acute liver injury but also increase susceptibility of the fibrotic response. Aging is associated with the severity and poor prognosis of various liver diseases including nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and liver transplantation. Summary Treatment of older patients with liver disease may require different or longer interventions. Transplantation of an older liver will be less tolerant of subsequent injury. Future studies are needed to understand more about the molecular mechanism of aging and contribute to the development of a noble treatment strategy that can block the progression of aging-induced liver diseases. PMID:25850346

  7. Fasciola hepatica: Specificity of a coproantigen ELISA test for diagnosis of fasciolosis in faecal samples from cattle and sheep concurrently infected with gastrointestinal nematodes, coccidians and/or rumen flukes (paramphistomes), under field conditions.

    PubMed

    Kajugu, P-E; Hanna, R E B; Edgar, H W; McMahon, C; Cooper, M; Gordon, A; Barley, J P; Malone, F E; Brennan, G P; Fairweather, I

    2015-09-15

    Chronic fasciolosis is often diagnosed by faecal egg counting (FEC), following concentration of the eggs in the sample by a zinc sulphate floatation method. However, concentration by a sedimentation technique gives improved sensitivity. Interpretation of FEC results for fasciolosis is complicated by factors such as the long pre-patent period and irregular egg shedding. Thus, FEC reduction tests (FECRT), when used alone, are not completely reliable for diagnosis of anthelmintic susceptibility or resistance in local fluke populations, especially when parasite burdens are small. A Fasciola hepatica coproantigen ELISA test has been introduced which more accurately reflects the presence of flukes in the host bile ducts in late pre-patent infections, and absence of flukes following successful chemotherapeutic intervention. The aim of the present study was to elucidate the specificity of the F. hepatica coproantigen ELISA technique, particularly regarding potential cross-reactivity with rumen fluke (paramphistome), gastrointestinal nematode and coccidian infections. The method involved parallel testing of a large battery of faecal samples from field-infected cattle and sheep using floatation and sedimentation FECs and coproantigen analysis. No evidence was found for significant false positivity in the F. hepatica coproantigen ELISA due to paramphistome, coccidian and/or gastrointestinal nematode co-infections. With sedimentation FECs less than 10 F. hepatica eggs per gram (epg), the likelihood of a positive coproantigen result for the sample progressively decreased. Diagnosis of fasciolosis should be based on consideration of both FEC and coproantigen ELISA findings, to ensure optimum sensitivity for pre-patent and low-level infections. PMID:26234898

  8. Robotic liver surgery.

    PubMed

    Leung, Universe; Fong, Yuman

    2014-10-01

    Robotic surgery is an evolving technology that has been successfully applied to a number of surgical specialties, but its use in liver surgery has so far been limited. In this review article we discuss the challenges of minimally invasive liver surgery, the pros and cons of robotics, the evolution of medical robots, and the potentials in applying this technology to liver surgery. The current data in the literature are also presented. PMID:25392840

  9. Robotic liver surgery

    PubMed Central

    Leung, Universe

    2014-01-01

    Robotic surgery is an evolving technology that has been successfully applied to a number of surgical specialties, but its use in liver surgery has so far been limited. In this review article we discuss the challenges of minimally invasive liver surgery, the pros and cons of robotics, the evolution of medical robots, and the potentials in applying this technology to liver surgery. The current data in the literature are also presented. PMID:25392840

  10. Statins and the Liver.

    PubMed

    Herrick, Cynthia; Bahrainy, Samira; Gill, Edward A

    2016-03-01

    Lipid lowering, particularly with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ("statins"), reduces the risk of cardiovascular disease. Patients with chronic liver disease present challenges to the use of lipid medications. In the case of most liver disorders, the concern has been one of safety. There is evidence that most lipid-lowering medications can be used safely in many situations, although large outcomes trials are lacking. This review examines lipid physiology and cardiovascular risk in specific liver diseases and reviews the evidence for lipid lowering and the use of statins in chronic liver disease. PMID:26893001

  11. Neonatal acute liver failure.

    PubMed

    Taylor, Sarah A; Whitington, Peter F

    2016-05-01

    Neonatal acute liver failure (NALF) is a rare disease about which there is little published data; however, NALF is an extremely important condition as it is distinct from acute liver failure seen in older children and adults. First, unlike acute liver failure in older patients, NALF can be diagnosed in an infant with cirrhosis. This is due to the fetal-neonatal continuum of liver disease, or the principle that neonatal liver failure may be the result of a liver disease that began in utero. Further differences exist in the mechanism of disease, diagnostic principles, and the common etiologies of NALF when compared with pediatric and adult acute liver failure. This review will address many of the distinguishing features of NALF and focus on the most common etiologies of NALF, including gestational alloimmune liver disease (GALD), the most common cause of NALF. Additionally, this review will provide insight into the pathogenesis, diagnosis, and treatment of this rare condition. Liver Transplantation 22 677-685 2016 AASLD. PMID:26946058

  12. Ectopic intracaval liver.

    PubMed

    Rafiei, Poyan; Sebastian, Sunit; Patel, Ramesh B; Roda, Manohar S

    2012-01-01

    Congenital abnormalities of the liver are rare with prior descriptions of lobar or segmental agenesis, Reidel's lobe, and ectopic hepatic lobes. Intrathoracic ectopic hepatic lobes have been reported in many instances; however, there is only one documented case of abnormally positioned liver tissue within the inferior vena cava (J Chapman-Fredricks, R Birusingh, M Ricci, M Rodriguez, Intracaval liver with cardiac extension. A new developmental anomaly? Fetal and Pediatric Pathology. 2010; 29:401-406). We report a second case of an ectopic intracaval liver defined as a mass in an adult who presented for abdominal pain and review the radiological findings. PMID:23154027

  13. Human Liver Progenitor Cells for Liver Repair

    PubMed Central

    Lombard, Catherine A.; Prigent, Julie; Sokal, Etienne M.

    2013-01-01

    Because of their high proliferative capacity, resistance to cryopreservation, and ability to differentiate into hepatocyte-like cells, stem and progenitor cells have recently emerged as attractive cell sources for liver cell therapy, a technique used as an alternative to orthotopic liver transplantation in the treatment of various hepatic ailments ranging from metabolic disorders to end-stage liver disease. Although stem and progenitor cells have been isolated from various tissues, obtaining them from the liver could be an advantage for the treatment of hepatic disorders. However, the techniques available to isolate these stem/progenitor cells are numerous and give rise to cell populations with different morphological and functional characteristics. In addition, there is currently no established consensus on the tests that need to be performed to ensure the quality and safety of these cells when used clinically. The purpose of this review is to describe the different types of liver stem/progenitor cells currently reported in the literature, discuss their suitability and limitations in terms of clinical applications, and examine how the culture and transplantation techniques can potentially be improved to achieve a better clinical outcome. PMID:26858860

  14. Nonalcoholic Fatty Liver Disease and Liver Transplantation.

    PubMed

    Pham, Tuan; Dick, Travis B; Charlton, Michael R

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is prevalent in the general population and a growing indication for liver transplant. Longer wait times and challenges with pretransplant survivorship are expected, underscoring the need for improved management of attendant comorbidities. Recognition with potential modification of obesity, sarcopenia, chronic kidney disease, and cardiovascular disease in patients with NAFLD may have important implications in the pretransplant and posttransplant periods. Although patients with NAFLD have generally favorable postoperative outcomes, they are at risk for developing recurrent disease in their allograft, driving the need for pharmacotherapies and dietary innovations appropriate for use in the posttransplant period. PMID:27063277

  15. [Multiple liver lesions accompanied by eosinophilia - a case report of fascioliosis].

    PubMed

    Trifina, Eva; Spenger, Johannes; Zandieh, Shahin; Haller, Jörg; Auer, Herbert; Osterreicher, Christian; Klaushofer, Klaus; Mikosch, Peter

    2011-09-01

    Fascioliosis is a zoonotic disease caused by Fasciola hepatica (common liver fluke). Initial clinical symptoms are frequently non-specific. Even after the development of liver tumors, a range of different underlying disorders will have to be considered. The rare cause of a parasitosis is not always included in the differential diagnostic work up. We report on a 41-year-old truck driver from Middle East who was admitted at our hospital due to ongoing upper abdominal pain, fatigue, night sweat and nausea lasting for weeks. Diagnostic investigation showed leucocytosis, high erythrocyte sedimentation rate, elevated liver values and IgE as well as blood eosinophilia. Radiological findings of the computed tomography were bilateral pulmonary lesions 3 mm in size and multiple hepatic lesions up to 4.5 cm in diameter. Due to the suspicion of a malignant disease, a liver biopsy was planned but cancelled after parasitological serology (Western blot and ELISA) revealed IgG-antibodies against F. hepatica. Detailed history gave evidence of a recent parasitological infection during a stay in Turkey with consumption of vegetable which were grown and washed with water from the local river. Eggs of the parasite could neither be found in analysis of duodenal secretion nor in examination of fecal culture. However, confirmation for the infection with F. hepatica was proved with another positive serology. The treatment with Triclabendazole (Egaten(®)) for two days with a total dosage of 2000 mg was followed by a remarkable recovery of the patient's symptoms and decrease of eosinophilia in the blood count just one month after treatment and normalization after four months. PMID:22016067

  16. Liver Cell Culture Devices

    PubMed Central

    Andria, B.; Bracco, A.; Cirino, G.; Chamuleau, R. A. F. M.

    2010-01-01

    In the last 15 years many different liver cell culture devices, consisting of functional liver cells and artificial materials, have been developed. They have been devised for numerous different applications, such as temporary organ replacement (a bridge to liver transplantation or native liver regeneration) and as in vitro screening systems in the early stages of the drug development process, like assessing hepatotoxicity, hepatic drug metabolism, and induction/inhibition studies. Relevant literature is summarized about artificial human liver cell culture systems by scrutinizing PubMed from 2003 to 2009. Existing devices are divided in 2D configurations (e.g., static monolayer, sandwich, perfused cells, and flat plate) and 3D configurations (e.g., liver slices, spheroids, and different types of bioreactors). The essential features of an ideal liver cell culture system are discussed: different types of scaffolds, oxygenation systems, extracellular matrixes (natural and artificial), cocultures with nonparenchymal cells, and the role of shear stress problems. Finally, miniaturization and high-throughput systems are discussed. All these factors contribute in their own way to the viability and functionality of liver cells in culture. Depending on the aim for which they are designed, several good systems are available for predicting hepatotoxicity and hepatic metabolism within the general population. To predict hepatotoxicity in individual cases genomic analysis might be essential as well. PMID:26998397

  17. Multiple listerial liver abscesses.

    PubMed Central

    Jenkins, D; Richards, J E; Rees, Y; Wicks, A C

    1987-01-01

    Hepatic involvement in listeriosis is uncommon in adults. Cases previously reported include three presenting as acute hepatitis and three of listerial liver abscesses found at necropsy. We report a case of multiple listerial liver abscesses. We believe this to be the first time this diagnosis has been made in a living patient. PMID:3428693

  18. Hypoxia and fatty liver

    PubMed Central

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-01-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease. PMID:25386057

  19. [Indications for liver transplant].

    PubMed

    Aguirre-Valadez, Jonathan; Torre, Aldo; Vilatobá, Mario; Contreras, Alan; Sánchez-Cedillo, Aczel; Antolinez-Motta, Jorge; García-Juárez, Ignacio

    2014-01-01

    Liver transplantation (LT) is the treatment of choice in selected patients with end-stage liver disease and in some with acute liver failure, hepatocellular carcinoma (HCC) and other diseases with no synthetic liver failure. Currently, LT has an overall survival > 90 % at 1 year. Proper selection of LT candidates is important given the shortage in organ donation. The allocation and priorization of organs to patients with chronic liver failure (CLF) in waiting lists, is determined by the MELD priority score (Model of End Stage Liver Disease). Indications for LT in patients with CLF are the same regardless of the etiology (any type of hepatic decompensation or development of HCC). Priority MELD is a variant to this classification used only in special cases such as in those with stable hepatopathy but severe extra-hepatic features (e.g., HCC or hepato-pulmonary syndrome). The indication for LT in patients with acute liver failure (ALF) and acute failure associated to chronic liver failure (ACLF) are not fully established; there are prognostic factors that may guide the decision for urgent LT and some centers, like the King's College Hospital criteria in the UK. Currently, LT is a therapeutic modality in some primary liver tumors (HCC, cholangiocarcinoma) and neuroendocrine liver metastatic tumors. These protocols have provided significant opportunities for long-term survival (> 70% at 5 years). The high demand and shortage of organs have fostered the development of new strategies to benefit more patients, such as the use of extended criteria donors, or "domino" transplants. This review focuses on the most relevant data on the different indications of LT. PMID:25729871

  20. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. PMID:24951302

  1. Discovery of intermediate hosts for two species of blood flukes Cardicola orientalis and Cardicola forsteri (Trematoda: Aporocotylidae) infecting Pacific bluefin tuna in Japan.

    PubMed

    Shirakashi, Sho; Tani, Kazuki; Ishimaru, Katsuya; Shin, Sang Phil; Honryo, Tomoki; Uchida, Hiro'omi; Ogawa, Kazuo

    2016-04-01

    Fish blood flukes (Aporocotylidae) are important pathogens of farmed finfish around the world. Among them, Cardicola spp. infecting farmed tuna are considered to be serious threats to tuna farming and have received tremendous attention. We conducted periodical samplings at a tuna farming site in Japan between January and May, 2015 to determine the life cycle of Cardicola spp. We collected over 4700 terebellid polychaetes from ropes, floats and frames of tuna culture cages and found nearly 400 infected worms. Sporocysts and cercariae found in Nicolea gracilibranchis were genetically identified as Cardicola orientalis by 28S and ITS2 ribosomal DNA sequences. This was the first discovery of the intermediate host for this parasite species. Infection prevalence and the abundance of N. gracilibranchis significantly varied between sampling points and the highest number of infected terebellids were collected from ropes. We also demonstrated morphologically and molecularly that asexual stages found in a single Amphitrite sp. (Terebellidae) and adult worms isolated from farmed juvenile tuna were Cardicola forsteri. This is the first report of C. forsteri in Pacific bluefin tuna (PBT) Thunnus orientalis in Japan. Our results demonstrated that all three species of Cardicola orientalis, C. forsteri and Cardicola opisthorchis exist in Japanese farmed PBTs and that they all use terebellid polychaetes as the intermediate hosts. PMID:26571413

  2. Molecular and functional characterization of a tandem-repeat galectin from the freshwater snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni

    PubMed Central

    Yoshino, Timothy P.; Dinguirard, Nathalie; Kunert, John; Hokke, Cornelius H.

    2008-01-01

    In the present study, a tandem-repeat type galectin was characterized from an embryonic cell line (Bge) and circulating hemocytes of the snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni. The predicted B. glabrata galectin (BgGal) protein of 32 kDa possessed 2 carbohydrate recognition domains, each displaying 6 of 8 conserved amino acids involved in galactoside-binding activity. A recombinant BgGal (rBgGal) demonstrated hemagglutinating activity against rabbit erythrocytes, which was specifically inhibited by galactose-containing sugars (lacNAc/lac > galNAc/gal). Although native galectin was immunolocalized in the cytoplasm of Bge cells and the plasma membrane of a subset of snail hemocytes (60%), it was not detected in cell-free plasma by Western blot analysis. The findings that rBgGal selectively recognizes the schistosome-related sugar, lacNAc, and strongly binds to hemocytes and the tegument of S. mansoni sporocysts in a sugar-inhibitable fashion suggest that hemocyte-bound galectin may be serving as pattern recognition receptor for this, or other pathogens possessing appropriate sugar ligands. Based on molecular and functional features, BgGal represents an authentic galectin, the first to be fully characterized in the medically-important molluscan Class Gastropoda. PMID:18280060

  3. Pathogenesis of liver cirrhosis

    PubMed Central

    Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

    2014-01-01

    Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions. PMID:24966602

  4. Proteoglycans in liver cancer.

    PubMed

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  5. Proteoglycans in liver cancer

    PubMed Central

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  6. Alcoholic liver disease

    PubMed Central

    Bruha, Radan; Dvorak, Karel; Petrtyl, Jaromir

    2012-01-01

    Alcohol use disorders affect millions of individuals worldwide. Alcohol consumption is directly associated with liver disease mortality and accounts for elevated social and economic costs. Alcoholic liver disease (ALD) may take the form of acute involvement (alcoholic hepatitis) or chronic liver disease (steatosis, steatohepatitis, fibrosis and cirrhosis). The severity and prognosis of alcohol-induced liver disease depends on the amount, pattern and duration of alcohol consumption, as well as on the presence of liver inflammation, diet, nutritional status and genetic predisposition of an individual. While steatosis is an almost completely benign disease, liver cirrhosis is associated with marked morbidity, mortality and life expectancy shortening. The median survival of patients with advanced cirrhosis is 1-2 years. Severe acute alcoholic hepatitis (AH) is associated with mortality as high as 50%. It has been managed with corticoids, pentoxifylline and enteral nutrition, although evidence based data are still conflicting. Some author suggest that pentoxifylline could be a better first-line treatment in patients with severe AH. Absolute abstinence is a basic condition for any treatment of acute or chronic ALD, the other therapeutical procedure being of a supportive nature and questionable significance. Acamprosate appears to be an effective treatment strategy for supporting continuous abstinence in alcohol dependent patients. Patients with advanced liver cirrhosis who demonstrably abstain can be considered for liver transplantation, which leads to a markedly prolonged life expectancy. The crucial step in ALD prevention is in the prevention of alcohol abuse, whereas the prevention of liver injury in active alcohol abusers is not clinically applicable. PMID:22489260

  7. Probiotics and liver disease.

    PubMed

    Sharma, Vishal; Garg, Shashank; Aggarwal, Sourabh

    2013-01-01

    Intestinal microbiota play an important role in health and disease. The gut-liver axis provides for an interaction between bacterial components like lipopolysaccharide and hepatic receptors (Toll-like receptors). Dysbiosis and altered intestinal permeability may modulate this interaction and therefore result in hepatic disorders or worsening of hepatic disorders. Administration of health-promoting microbial strains may help ameliorate these harmful interactions and hepatic disorders. This review focuses on changes in gut microbiota in the context of liver disease and possible roles of probiotics, prebiotics, and synbiotics in liver disease. PMID:24361022

  8. Gut-liver immunity.

    PubMed

    Trivedi, Palak J; Adams, David H

    2016-05-01

    The liver contributes to immune surveillance against pathogens entering via the gut and is itself influenced by alterations in mucosal immune responses and the microbiome. Mucosal immunity is also implicated in autoimmune liver diseases that associate with inflammatory bowel disease (IBD), and in steatohepatitis where compromised enteric barrier function and altered bacterial sensing drive liver inflammation. In this article, we discuss recent advances in our understanding of how dysregulated mucosal immune responses result in hepatobiliary injury; specifically through defective intestinal barrier function, changes in the enteric microbiome and loss of immune tolerance, and via shared leucocyte recruitment pathways. PMID:26686270

  9. Managing alcoholic liver disease

    PubMed Central

    2015-01-01

    Alcoholic liver disease continues to be a significant cause of liver-related morbidity and mortality throughout the world. A number of diagnostic and prognostic models have been developed in the management of this condition, although specific roles for liver biopsy still remain particularly in the setting of alcoholic hepatitis. Despite a large number of recent treatment trials, the ideal pharmacotherapy approach remains undefined. Most essential is the supportive care and focus on abstinence and nutrition. Owing in part to a great deal of attention from governmental funding sources, a number of new treatment approaches are undergoing rigorous evaluation, hopefully providing future treatment options in this very severe condition. PMID:26523266

  10. Robotic liver resection technique.

    PubMed

    Hart, Marquis E; Precht, Andrew

    2013-01-01

    The robotic approach to hepatic resection has evolved because of advances in laparoscopy and digital technology and based on the modern understanding of hepatic anatomy. Robotic technology has allowed for the development of a minimally invasive approach, which is conceptually similar to the open approach. The major differences are improved visualization and smaller incisions without a haptic interface. As a result, the operative strategy is reliant on visual cues and knowledge of hepatic surgical anatomy. Development of a robotic liver resection program ideally occurs in the setting of a comprehensive liver program with significant experience in all aspects of surgical liver care. PMID:23528723

  11. Liver Transplantation for Alcohol-Related Liver Disease.

    PubMed

    Choudhary, Narendra S; Kumar, Naveen; Saigal, Sanjiv; Rai, Rahul; Saraf, Neeraj; Soin, Arvinder S

    2016-03-01

    Alcoholic liver disease (ALD) is a common indication for liver transplantation. It is a much debated indication for deceased donor liver transplantation due to organ shortage and potential of alcohol relapse after liver transplantation. A six-month abstinence before liver transplantation is required at most centers to decrease chances of alcohol relapse after liver transplantation. However, this rule is not relevant for patients with severe alcoholic hepatitis or severely decompensated patients who are unlikely to survive till 6 months. Long-term care of these patients after liver transplantation includes assessment of relapse, smoking, and surveillance of de novo malignancies. Current review discusses role of abstinence, factors affecting alcohol relapse, liver transplantation for alcoholic hepatitis, role of living donor liver transplantation, and long-term care of ALD patients who undergo liver transplantation. PMID:27194896

  12. Liver (Hepatocellular) Cancer Prevention

    MedlinePlus

    ... with hepatitis A usually get better without treatment. Hepatitis B Hepatitis B is caused by contact with the ... factors may increase the risk of liver cancer: Hepatitis B and C Having chronic hepatitis B or chronic ...

  13. Research Areas: Liver Disease

    MedlinePlus

    ... weight control and nutrition, urologic diseases, endocrine and metabolic diseases, and blood diseases La Información de la Salud ... Program Digestive Disease and Nutrition Endocrine Disease and Metabolic Disease Hematologic Disease Kidney Disease Liver Disease Obesity Urologic ...

  14. Alcoholic liver disease

    MedlinePlus

    ... weight loss Nausea or belly pain Small, red spider-like blood vessels on the skin As liver ... result of too much fluid Reddened palms Red spider-like blood vessels on the skin Small testicles ...

  15. Pyogenic liver abscess

    MedlinePlus

    ... of liver abscesses, including: Abdominal infection, such as appendicitis , diverticulitis , or a perforated bowel Infection in the ... often, surgery is required. You will also receive antibiotics for about 4 - 6 weeks. Sometimes, antibiotics alone ...

  16. Pediatric liver transplantation

    PubMed Central

    Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

    2009-01-01

    In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089

  17. Cod Liver Oil

    MedlinePlus

    ... cod liver oil on their skin to speed wound healing. When taken in appropriate doses by mouth, cod ... young children. Heart disease. Systemic lupus erythematosus (SLE). Wound healing. Glaucoma. Other conditions. More evidence is needed to ...

  18. [Diabetes in liver cirrhosis].

    PubMed

    García-Compeán, Diego; Jáquez-Quintana, Joel O; González-González, José A; Lavalle-González, Fernando J; Villarreal-Pérez, Jesús Z; Maldonado-Garza, Hector J

    2013-01-01

    The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease. PMID:23628170

  19. Liver (Hepatocellular) Cancer Screening

    MedlinePlus

    ... United States than in other parts of the world. Liver cancer is uncommon in the United States, ... is the fourth most common cancer in the world. In the United States, men, especially Chinese American ...

  20. Analgesia after liver transplantation

    PubMed Central

    Milan, Zoka

    2015-01-01

    This article addresses postoperative analgesia in patients with end-stage liver disease who have undergone liver transplantation (LT). Postoperative analgesia determines how patients perceive LT. Although important, this topic is underrepresented in the current literature. With an increased frequency of fast tracking in LT, efficient intra- and postoperative analgesia are undergoing changes. We herein review the current literature, compare the benefits and disadvantages of the therapeutic options, and make recommendations based on the current literature and clinical experience. PMID:26413222

  1. [Advances in liver surgery].

    PubMed

    Grill, W

    1984-01-12

    In corroboration of previous research results our own investigations show that advances in liver surgery are achieved above all by early and considerably extended clinical diagnosis as well as by decisively improved surgical technique. Supporting measures such as mebendazole medication in the surgical management of echinococcosis have an important share in successful treatment. However, there is no doubt that, even today, liver surgery is not the routine operation ranking equal with biliary or gastric surgery. PMID:6698461

  2. Sorafenib Tosylate in Treating Patients With Liver Cancer Who Have Undergone a Liver Transplant

    ClinicalTrials.gov

    2015-03-25

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

  3. Update in liver transplantation.

    PubMed Central

    Wong, W. W.; Bain, V. G.

    1999-01-01

    OBJECTIVE: To review recent developments in liver transplantation with particular emphasis on issues relevant to patient care before and after transplantation. QUALITY OF EVIDENCE: Preference was given to recent studies with well-designed cohort methods and large numbers of study subjects. Data on natural history are summarized from large databases in Canada and the United States. Due to the nature of the subjects involved, most treatment studies are open studies or consecutive series rather than randomized controlled trials. MAIN MESSAGE: Substantial advances in liver transplantation have established it as an effective treatment for most end-stage liver diseases, with 1-year survival rates higher than 85% in many centres. Early referral by family physicians and careful patient selection by transplant centres remain crucial to continued success. Managing these patients requires special care from family physicians because of post-transplantation immunosuppression, increased risk of opportunistic infection, and transplantation-associated medical problems. Other unresolved issues include recurrence of disease (hepatitis B and C, and malignancy) and an ongoing shortage of organs. CONCLUSIONS: Liver transplantation is an effective form of therapy for end-stage liver disease, improving both patients' likelihood of survival and their quality of life. Because medical care of liver transplant patients is so complex, coordinated efforts between primary care physicians and transplant teams are crucial. PMID:10349068

  4. Fortuitously discovered liver lesions

    PubMed Central

    Dietrich, Christoph F; Sharma, Malay; Gibson, Robert N; Schreiber-Dietrich, Dagmar; Jenssen, Christian

    2013-01-01

    The fortuitously discovered liver lesion is a common problem. Consensus might be expected in terms of its work-up, and yet there is none. This stems in part from the fact that there is no preventive campaign involving the early detection of liver tumors other than for patients with known liver cirrhosis and oncological patients. The work-up (detection and differential diagnosis) of liver tumors comprises theoretical considerations, history, physical examination, laboratory tests, standard ultrasound, Doppler ultrasound techniques, contrast-enhanced ultrasound (CEUS), computed tomography and magnetic resonance imaging, as well as image-guided biopsy. CEUS techniques have proved to be the most pertinent method; these techniques became part of the clinical routine about 10 years ago in Europe and Asia and are used for a variety of indications in daily clinical practice. CEUS is in many cases the first and also decisive technical intervention for detecting and characterizing liver tumors. This development is reflected in many CEUS guidelines, e.g., in the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 as well as the recently published World Federation for Ultrasound in Medicine and Biology-EFSUMB guidelines 2012. This article sets out considerations for making a structured work-up of incidental liver tumors feasible. PMID:23745019

  5. Autoimmune liver disease, autoimmunity and liver transplantation.

    PubMed

    Carbone, Marco; Neuberger, James M

    2014-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune process is not clear. In this manuscript, we review novel findings about disease processes and mechanisms that lead to autoimmunity in the liver and their possible involvement in the immune response vs. the graft after LT. PMID:24084655

  6. Neuropilins and liver

    PubMed Central

    Elpek, Gülsüm Özlem

    2015-01-01

    Neuropilins (NRPs) are highly conserved transmembrane glycoproteins that possess pleiotropic functions. Neuropilin-1 (NRP1) and its homologue neuropilin-2 interact as coreceptors with both class 3 semaphorins and vascular endothelial growth factor and are involved in neuronal guidance and angiogenesis, respectively. The contribution of NRPs to tumor angiogenesis has been highlighted in previous studies, leading to the development of NRP antagonists as novel anti-angiogenesis therapies. However, more recent studies have demonstrated that NRPs have a much broader spectrum of activity in the integration of different pathways in physiological and pathological conditions. A few studies investigated the role of NRPs in both malignant and non-neoplastic liver diseases. In normal liver, NRP1 is expressed in hepatic stellate cells and liver sinusoidal endothelial cells. NRP1 expression in hepatocytes has been associated with malignant transformation and may play an important role in tumor behavior. A contribution of NRPs in sinusoidal remodeling during liver regeneration has been also noted. Studies in chronic liver diseases have indicated that, besides its influence on angiogenesis, NRP1 might contribute to the progression of liver fibrosis owing to its effects on other growth factors, including transforming growth factor β1. As a result, NRP1 has been identified as a promising therapeutic target for future antifibrotic therapies based on the simultaneous blockade of multiple growth factor signaling pathways. In this review, the structure of NRPs and their interactions with various ligands and associated cell surface receptors are described briefly. The current understanding of the roles of the NRPs in liver diseases including tumors, regeneration and fibrogenesis, are also summarized. PMID:26109793

  7. THEMES OF LIVER TRANSPLANTATION

    PubMed Central

    Starzl, Thomas E.; Fung, John J.

    2010-01-01

    Liver transplantation was the product of 5 interlocking themes. These began in 1958-59 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g. familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and ALG. With this regimen, the world’s longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979) which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as healthcare standards, the ethical, legal, equity, and the other humanism issues of Theme V have been resolved less conclusively than the medical-scientific problems of Themes I–IV. PMID:20235333

  8. [Epistemology of liver cirrhosis].

    TOXLINE Toxicology Bibliographic Information

    Coppo M; Borghi A

    1990-04-01

    Critical considerations are expressed on scientific approach to liver cirrhosis, a nosological entity based on both analytical inquiry and long term observation of a large number of cirrhotic patients. The main points taken into consideration are: the etiopathogenesis of cirrhosis; a systematic of diagnostic elements; some preventional aspects of the disease and of its major sequelae. In the histogenetical analysis, the following steps are identified and analysed: a) hepatocellular death (necrosis), b) inflammatory process, c) fibrosis, d) hepatocellular regeneration and disorganized vascular architecture as a consequence of nodular regeneration. The hepatotoxic action of the three most studied and widespread etiologic agents of cirrhosis, alcohol, HBV, iron, is also considered. Finally, as a last pathogenetic step and peculiar to liver cirrhosis, the complex vascular rearrangement that leads to a relative increase of the liver blood flow is analysed. Clinical experience suggests a distinction between active and inactive liver cirrhosis. In the former we find a chronic active hepatitis associated with nodular regeneration and subsequent compensatory blood flow rearrangement. No signs of chronic active hepatitis can be found in the latter which is characterized by irreversible alteration of the liver architecture, reduction of the liver function and hemodynamic rearrangement (portal and arterial). Both nosologic entities can be either clinically characterized or not by symptoms of the major sequelae and complications of cirrhosis. On the basis of the clinical experience, among the complications of cirrhosis spontaneous bacterial peritonitis, gastrointestinal bleeding, hepatorenal syndrome and hepatocarcinoma appear to have a great prognostic value. Association between hepatocarcinoma and liver cirrhosis, which seems to be independent of single etiologic factors of cirrhosis itself, also has a great reliance.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. De novo assembly and characterization of the transcriptome of the pancreatic fluke Eurytrema pancreaticum (trematoda: Dicrocoeliidae) using Illumina paired-end sequencing.

    PubMed

    Liu, Guo-Hua; Xu, Min-Jun; Song, Hui-Qun; Wang, Chun-Ren; Zhu, Xing-Quan

    2016-01-15

    Eurytrema pancreaticum is one of the most common trematodes living in the pancreatic and bile ducts of ruminants and also occasionally infects humans, causing eurytremiasis. In spite of its economic and medical importance, very little is known about the genomic resources of this parasite. Herein, we performed de novo sequencing, assembly and characterization of the transcriptome of adult E. pancreaticum. Approximately 36.4 million high-quality clean reads were obtained, and the length of the transcript contigs ranged from 66 to 19,968 nt with mean length of 479 nt and N50 length of 1094 nt, and then 23,573 unigenes were assembled. Of these unigenes, 15,353 (65.1%) were annotated by blast searches against the NCBI non-redundant protein database. Among these, 15,267 (64.8%), 2732 (11.6%) and 10,354 (43.9%) of the unigenes had significant similarity with proteins in the NR, NT and Swiss-Prot databases, respectively. 5510 (23.4%) and 4567 (19.4%) unigenes were assigned to GO and COG, respectively. 8886 (37.7%) unigenes were identified and mapped onto 254 pathways in the KEGG Pathway database. Furthermore, we found that 105 (1.18%) unigenes were related to pancreatic secretion and 61 (0.7%) to pancreatic cancer. The present study represents the first transcriptome of any members of the family Dicrocoeliidae, which has little genomic information available in the public databases. The novel transcriptome of E. pancreaticum should provide a useful resource for designing new strategies against pancreatic flukes and other trematodes of human and animal health significance. PMID:26494161

  10. Novel strategies for liver support in acute liver failure.

    PubMed

    Butler, A; Friend, P J

    1997-01-01

    At present, the treatment of a patient in acute liver failure is based upon scrupulous intensive care. In those patients whose condition deteriorates, emergency liver transplantation must be considered. There would be great benefit if it were possible to provide treatment which would stabilise the condition of a patient in acute liver failure. Thus, there is great incentive to develop a means of artificial liver support. Over many years, a considerable array of therapeutic strategies has been investigated. These can be considered in four main categories: plasma exchange, haemofiltration, extra-corporeal liver assist devices (ELAD), extra-corporeal liver perfusion (ECLP). Finally, the role of xenotransplantation is considered. PMID:9536523

  11. Gut microbiota and liver diseases.

    PubMed

    Minemura, Masami; Shimizu, Yukihiro

    2015-02-14

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  12. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  13. Transjugular Liver Biopsy

    PubMed Central

    Behrens, George; Ferral, Hector

    2012-01-01

    Liver biopsy is considered the gold standard for the evaluation of acute and chronic liver disorders. Transjugular liver biopsy (TJLB) was described by Dotter in 1964 and clinically performed for the first time by Hanafee in 1967. TJLB consists of obtaining liver tissue through a rigid cannula introduced into one of the hepatic veins, typically using jugular venous access. The quality of the TJLB specimens has improved so much that the samples obtained by this method are comparable with those obtained with the percutaneous technique. TJLB is indicated for patients with coagulopathy, ascites, peliosis hepatis, morbid obesity, liver transplant, or in patients undergoing a transjugular intrahepatic portosystemic shunt procedure. The technical success rate for a TJLB procedure ranges from 87 to 97%. Sample fragmentation has been reported in 14 to 25% of the TJLB samples. The complication rates are low and range between 1.3% and 6.5%. The purpose of this article is to provide a review of the fundamental aspects of the TJLB procedure, including technique, indications, contraindications, results, and complications. PMID:23729981

  14. Angiogenesis and liver fibrosis

    PubMed Central

    Elpek, Gülsüm Özlem

    2015-01-01

    Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes place in chronic liver diseases (CLDs) that are characterized by inflammation and progressive fibrosis. Because anti-angiogenic therapy has been found to be efficient in the prevention of fibrosis in experimental models of CLDs, it is suggested that blocking angiogenesis could be a promising therapeutic option in patients with advanced fibrosis. Consequently, efforts are being directed to revealing the mechanisms involved in angiogenesis during the progression of liver fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis are closely related in both clinical and experimental conditions. Hypoxia is a major inducer of angiogenesis together with inflammation and hepatic stellate cells. These profibrogenic cells stand at the intersection between inflammation, angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This review mainly focuses to give a clear view on the relevant features that communicate angiogenesis with progression of fibrosis in CLDs towards the-end point of cirrhosis that may be translated into future therapies. The pathogenesis of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non-alcoholic fatty liver disease and alcoholic liver disease are also discussed to emphasize the various mechanisms involved in angiogenesis during liver fibrogenesis. PMID:25848465

  15. Anesthesia for liver transplantation.

    PubMed

    Dalal, Aparna

    2016-01-01

    Patients with end stage liver disease (ESLD) have complex problems such as cirrhotic cardiomyopathy, coronary artery disease, hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), hepatic encephalopathy, intracranial hypertension, (ICP), left ventricular outflow tract obstruction (LVOTO), high Model of end liver disease (MELD) scores, hyponatremia, and coagulopathies. The anesthesia management for liver transplantation can be very complex, dynamic and challenging. Anesthesia agents affect hepatic blood flow and anesthetic drug distribution, metabolism and elimination maybe altered in end stage liver disease. Other non-anesthetic agents such as nitric oxide, epoprosterenol, THAM, hypertonic saline, fibrinogen concentrates, fresh frozen plasma, platelets, packed red blood cells, recombinant plasminogen activator, calcium chloride, epinephrine etc. may play a vital role in the perioperative management of these patients. Intraoperative hemostasis and coagulation management can be very arduous as these patients may bleed or be at risk for thrombosis. Monitoring modalities such as Thromboelastography (TEG), Transcranial Doppler (TCD), Transesophageal Echocardiography (TEE), Bispectral Index (BIS) and Optic Nerve Sheath Diameter (ONSD) ultrasound play a significant role in various circumstances. Surgical techniques include complete or partial occlusion of the inferior vena cava (IVC) with or without use of venovenous bypass (VVBP) or portocaval shunts. Post reperfusion syndrome (PRS) is a crucial event in this procedure, where patients may experience arrhythmia and/or cardiac arrest. Anesthetic handling of this phase has been recapitulated in detail. Provision of anesthesia services to the living liver transplant donor and pain management has been outlined. PMID:26118926

  16. Stereoscopic liver surface reconstruction

    PubMed Central

    Karwan, Adam; Rudnicki, Jerzy; Wróblewski, Tadeusz

    2012-01-01

    The paper presents a practical approach to measuring liver motion, both respiratory and laparoscopic, with a tool guided in the operating room. The presented method is based on standard operating room equipment, i.e. rigid laparoscopic cameras and a single incision laparoscopic surgery trocar. The triangulation algorithm is used and stereo correspondence points are marked manually by two independent experts. To calibrate the cameras two perpendicular chessboards, a pinhole camera model and a Tsai algorithm are used. The data set consists of twelve real liver surgery video sequences: ten open surgery and two laparoscopic, gathered from different patients. The setup equipment and methodology are presented. The proposed evaluation method based on both calibration points of the chessboard reconstruction and measurements made by the Polaris Vicra tracking system are used as a reference system. In the analysis stage we focused on two specific goals, measuring respiration and laparoscopic tool guided liver motions. We have presented separate examples for left and right liver lobes. It is possible to reconstruct liver motion using the SILS trocar. Our approach was made without additional position or movement sensors. Diffusion of cameras and laser for distance measurement seems to be less practical for in vivo laparoscopic data, but we do not exclude exploring such sensors in further research. PMID:23256023

  17. Imaging in pediatric liver transplantation.

    PubMed

    Monti, L; Soglia, G; Tomà, P

    2016-05-01

    Liver transplantation has become an established curative treatment in adult patients with acute or chronic end-stage liver diseases. In pediatric cases the number of cadaveric donor livers is not sufficient and to overcome the shortage of appropriate-sized whole liver grafts, technical variants of liver transplantation have been practiced. Reduced-size cadaveric and split cadaveric allografts have become an important therapeutic option, expanding the availability of size-appropriate organs for pediatric recipients with terminal liver disease. The number of pediatric deaths awaiting liver transplantation has been reduced by the introduction of living-related liver transplantation, developed to overcome the shortage of suitable grafts for children. It is important for radiologists to know that children have distinct imaging of liver transplantation that distinguish them from adults. A multidisciplinary pediatric liver transplantation team should be skilled in pediatric conditions and in associated processes, risks and complications. Radiologists should know the common pediatric liver diseases that lead to liver transplantation, the anastomotic techniques and the expected postoperative imaging findings. The aim of this study is to illustrate the role of non-invasive imaging such us ultrasonography, color Doppler ultrasonography, multidetector computed tomography and magnetic resonance imaging in the evaluation of pediatric liver transplantation and in potential liver donors. PMID:26909515

  18. Liver disease in the adolescent.

    PubMed

    Mavis, Alisha M; Alonso, Estella M

    2015-02-01

    This article discusses common liver diseases in the adolescent. Briefly reviewed is the evaluation of the adolescent with new-onset liver enzyme elevation. Then the article discusses common liver diseases, such as nonalcoholic fatty liver disease, hepatitis, metabolic disease, biliary atresia, cystic fibrosis, and inherited disorders of cholestasis. Finally, a management approach to the adolescent with liver disease is outlined, noting the challenges that must be addressed to effectively care for not only liver disease in the adolescent but also the patient as a whole. PMID:25454303

  19. Liver involvement in systemic infection

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2014-01-01

    The liver is often involved in systemic infections, resulting in various types of abnormal liver function test results. In particular, hyperbilirubinemia in the range of 2-10 mg/dL is often seen in patients with sepsis, and several mechanisms for this phenomenon have been proposed. In this review, we summarize how the liver is involved in various systemic infections that are not considered to be primarily hepatotropic. In most patients with systemic infections, treatment for the invading microbes is enough to normalize the liver function tests. However, some patients may show severe liver injury or fulminant hepatic failure, requiring intensive treatment of the liver. PMID:25276279

  20. Alcoholic liver disease: Treatment

    PubMed Central

    Suk, Ki Tae; Kim, Moon Young; Baik, Soon Koo

    2014-01-01

    The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

  1. Alcoholic liver disease: treatment.

    PubMed

    Suk, Ki Tae; Kim, Moon Young; Baik, Soon Koo

    2014-09-28

    The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

  2. [Living donor liver transplantation].

    PubMed

    Tanaka, K; Kaihara, S

    2003-10-01

    Liver transplantation has evolved into the standard treatment for numerous endstage liver diseases. The increase of organ shortages led to living organ donation. In 1988 living donor liver transplantation (LDLT) was performed for the first time. Since then multiple difficulties associated with LDLT have been solved. In Kyoto we can look back on more than 900 transplantations since the initiation of our LDLT program in 1990, which is the oldest in Japan and the largest in the world. In the following we review our extensive experience with special focus on issues such as donor safety, results after LDLT, and potential complications in the recipient. Further, graft size mismatching, venous drainage from anterior segment of the right lobe graft, LDLT for hepatocellular carcinoma, AB0-incompatible transplantation, and recurrence of hepatitis C infection, which are still unsolved problems in LDLT, are described and future directions are indicated. PMID:14605737

  3. [Complications of liver cirrhosis].

    PubMed

    Wittenburg, H; Tennert, U; Berg, T

    2011-09-01

    The occurrence of complications increases the mortality in patients with cirrhosis of the liver. Therefore, early detection and treatment of complications of cirrhosis is of major importance. Following diagnosis of cirrhosis, a screening gastroscopy detects esophageal varices. Primary prevention of variceal bleeding can be initiated with β-receptor antagonists or variceal band ligation. With the first episode of ascites or the manifestation of other complications of cirrhosis such as hepatic encephalopathy and hepatorenal syndrome, a paracentesis excludes spontaneous bacterial peritonitis. Hepatorenal syndrome can be treated with a combination of vasopressors and albumine. Furthermore, occurrence of complications in patients with cirrhosis of the liver should prompt the evaluation of an indication for liver transplantation. PMID:21611819

  4. Liver physiology and liver diseases in the elderly

    PubMed Central

    Tajiri, Kazuto; Shimizu, Yukihiro

    2013-01-01

    The liver experiences various changes with aging that could affect clinical characteristics and outcomes in patients with liver diseases. Both liver volume and blood flow decrease significantly with age. These changes and decreased cytochrome P450 activity can affect drug metabolism, increasing susceptibility to drug-induced liver injury. Immune responses against pathogens or neoplastic cells are lower in the elderly, although these individuals may be predisposed to autoimmunity through impairment of dendritic cell maturation and reduction of regulatory T cells. These changes in immune functions could alter the pathogenesis of viral hepatitis and autoimmune liver diseases, as well as the development of hepatocellular carcinoma. Moreover, elderly patients have significantly decreased reserve functions of various organs, reducing their tolerability to treatments for liver diseases. Collectively, aged patients show various changes of the liver and other organs that could affect the clinical characteristics and management of liver diseases in these patients. PMID:24379563

  5. Eosinophilic Liver Infiltration

    PubMed Central

    Figueroa Rivera, Ivonne; Toro, Doris H.; Gutierrez, Jose; Acosta, Eduardo

    2015-01-01

    Eosinophilic liver infiltration is a commonly encountered focal eosinophil-related inflammation with or without necrosis, which can be seen on computed tomography (CT) in the presence of peripheral eosinophilia. Although this entity has a relatively benign course, it is related to numerable conditions for which diagnosis may be challenging and requires substantial diagnostic work-up for proper management and care of the underlying disease. We report a case of a 60-year-old man who presented with a 1-week history of right upper quadrant abdominal pain with multiple ill-defined liver hypodensities associated with significant eosinophilia. PMID:26504883

  6. Obesity and liver transplantation

    PubMed Central

    Ayloo, Subhashini; Armstrong, John; Hurton, Scott; Molinari, Michele

    2015-01-01

    The percentage of overweight and obese patients (OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation (LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed. PMID:26421262

  7. Neoplasms of the liver

    SciTech Connect

    Okuda, K.; Ishak, K.G.

    1987-01-01

    Primary Liver Cancer is perhaps the most prevalent malignancy in the world, particularly in South East Asia and Africa. After the discovery of hepatitis B virus as a cause of chronic liver disease often terminating cirrhosis and hepatocellular carcinoma, and, more recently, the integration of viral DNA into host chromosomal DNA, the progress made in this field has been remarkable. This book contains 35 chapters and covers all topical aspects, such as oncogenes, epidemiology, carcinogenic role of hepatitis viruses, histopathology, new imaging techniques and new treatment modalities that include ultrasound-guided intratumor injections of ethanol and targeting chemotherapy.

  8. Stem Cells and Liver Regeneration

    PubMed Central

    DUNCAN, ANDREW W.; DORRELL, CRAIG; GROMPE, MARKUS

    2011-01-01

    One of the defining features of the liver is the capacity to maintain a constant size despite injury. Although the precise molecular signals involved in the maintenance of liver size are not completely known, it is clear that the liver delicately balances regeneration with overgrowth. Mammals, for example, can survive surgical removal of up to 75% of the total liver mass. Within 1 week after liver resection, the total number of liver cells is restored. Moreover, liver overgrowth can be induced by a variety of signals, including hepatocyte growth factor or peroxisome proliferators; the liver quickly returns to its normal size when the proliferative signal is removed. The extent to which liver stem cells mediate liver regeneration has been hotly debated. One of the primary reasons for this controversy is the use of multiple definitions for the hepatic stem cell. Definitions for the liver stem cell include the following: (1) cells responsible for normal tissue turnover, (2) cells that give rise to regeneration after partial hepatectomy, (3) cells responsible for progenitor-dependent regeneration, (4) cells that produce hepatocyte and bile duct epithelial phenotypes in vitro, and (5) transplantable liver-repopulating cells. This review will consider liver stem cells in the context of each definition. PMID:19470389

  9. The Virtual Liver: Modeling Chemical-Induced Liver Toxicity

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver) project is aimed at modeling chemical-induced processes in hepatotoxicity and simulating their dose-dependent perturbations. The v-Liver embodies an emerging field of research in computational tissue modeling that integrates molecular and cellul...

  10. Plants Consumption and Liver Health

    PubMed Central

    Guan, Yong-Song; He, Qing

    2015-01-01

    The liver is a very important organ with a lot of functions for the host to survive. Dietary components are essential for and can be beneficial or detrimental to the healthy or diseased liver. Plants food is an essential part of the human diet and comprises various compounds which are closely related to liver health. Selected food plants can provide nutritional and medicinal support for liver disease. At the present, the knowledge of the effects of plants on the liver is still incomplete. The most urgent task at the present time is to find the best dietary and medicinal plants for liver health in an endless list of candidates. This review article updates the knowledge about the effects of plants consumption on the health of the liver, putting particular emphasis on the potential beneficial and harmful impact of dietary and medicinal plants on liver function. PMID:26221179

  11. Liver Disease and Pulmonary Hypertension

    MedlinePlus

    Liver Disease Pulmonary & PH Hypertension Did you know that if you have liver disease, you are at risk for pulmonary hypertension? www.PHAssociation.org About Pulmonary Hypertension PULMONARY HYPERTENSION, OR PH, is complex and often misunderstood. PH means high ...

  12. Interventional Treatments for Liver Disease

    MedlinePlus

    ... stent placement Cancer - bone Cancer - breast Cancer - kidney Cancer - liver Cancer - lung Deep vein thrombosis Endovascular Treatment of CCSVI ... Obstruction In some patients, such as those with liver cancer or individuals who have had an injury to ...

  13. Coffee and liver health.

    PubMed

    Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

    2014-01-01

    Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients. PMID:25291138

  14. Glycosylation and Liver Cancer

    PubMed Central

    Mehta, Anand; Herrera, Harmin; Block, Timothy

    2015-01-01

    Liver cancer is the 5th most common cancer, but the 2nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non –viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2–7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development. PMID:25727150

  15. Alcoholic Liver Disease.

    PubMed

    Abittan; Lieber

    1999-02-01

    The traditional approach to alcoholism is treatment of underlying psychological and behavioral problems. Earlier and more direct avenues to prevent or counteract alcohol's effects include a focus on early detection of alcoholism, using, in part, biochemical markers of heavy drinking such as carbohydrate-deficient transferrin (CDT) and screening, among heavy users of alcohol, for signs of medical complications. Only a few heavy drinkers eventually develop liver cirrhosis. Because no practical genetic markers exist indicating who will develop fibrosis and cirrhosis, heavy drinkers who have signs of liver injury should undergo liver biopsy to determine whether they have perivenular fibrosis, a recognized precursor lesion to cirrhosis. Those who do should start intense treatment efforts, such as correction of nutritional deficits, curbing alcohol consumption, and participation in ongoing controlled trials. Some "supernutrients" have been effective in baboons, including S-adenosylmethionine for the treatment of alcohol-induced liver injury and polyenylphosphatidylcholine for the prevention of fibrosis. Both drugs are now being tested in humans. Prednisolone improves survival in patients with alcoholic hepatitis who have either spontaneous hepatic encephalopathy or a high "discriminant function." PMID:11096576

  16. Ton That Tung's livers.

    PubMed

    Helling, Thomas S; Azoulay, Daniel

    2014-06-01

    Born in the early 20th century, the Vietnamese surgeon Ton That Tung received his medical education in French colonial Indochina at the fledgling l'Ecole de Médecine de Hanoi, the first indigenous medical school in Southeast Asia. The benefactor of a postgraduate position at the medical school, Ton That Tung subsequently obtained his surgical training at the Phù Doãn Hospital in Hanoi and concurrently developed a passion for the study of liver anatomy, pathology, and surgery. His contributions to an understanding of liver anatomy based on meticulous dissection of autopsy specimens antedated and rivaled later work by the famous Western anatomists Couinaud, Healey, Schroy, and others. Ton That Tung's contributions, however, were overshadowed by the intense national struggles of the Vietnamese to establish independent rule and self-governance from the French and by eventual alignment with eastern bloc Communist countries, thus isolating much of his work behind the "Iron Curtain" until well after the end of the Cold War. Nevertheless, Ton That Tung remains a pioneer in liver anatomy and liver surgery. His commitment to surgical science and, more importantly, to the Vietnamese people stands as a tribute to the tireless pursuit of his ideals. PMID:24335785

  17. The EPA Liver Project

    EPA Science Inventory

    The v-Liver is part of a broader EPA effort on Virtual Tissues (VT) aimed at reducing the magnitude and spectrum of animal testing by integrative in silico and in vitro models, which recapitulate the properties of intact organs. The other VT projects include the Virtual Embryo (...

  18. Non-Alcoholic Fatty Liver Disease (NAFLD)

    MedlinePlus

    Non-Alcoholic Fatty Liver Disease What is Non-alcoholic fatty liver disease (NAFLD)? FAT N AFLD is a name ... liver may occur with resultant hepatitis called non-alcoholic steatohepatitis (NASH). This condition can lead to liver ...

  19. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  20. How Is Liver Cancer Found?

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Liver Cancer Download Printable Version [PDF] » View Overview Guide » Español » ... the topics below to get started. What Is Liver Cancer? What is liver cancer? What are the key ...

  1. SYBR, TaqMan, or both: highly sensitive, non-invasive detection of Cardicola blood fluke species in Southern Bluefin Tuna (Thunnus maccoyii).

    PubMed

    Polinski, Mark; Hamilton, Dylan Belworthy; Nowak, Barbara; Bridle, Andrew

    2013-09-01

    Three species of blood fluke from the genus Cardicola are known to parasitize and cause disease in Bluefin Tunas--C. forsteri, C. orientalis, and C. opisthorchis. Although initially believed to be separated by geography and host specificity, recent identification of at least two Cardicola spp. concurrently present within all three Bluefin species has raised questions concerning pathogenicity, relative abundance, and distribution of these parasites within Bluefin populations. Here, we present sensitive and differential real-time qPCR nucleic acid detection of these Cardicola spp. by targeting the ITS2 region of the parasite rDNA for PCR amplification. A limit of sensitivity of 1-5 genome copy equivelents was achieved for each of the three Cardicola species tested without cross-species or host genomic amplification. Similar sensitivity was further achieved in the presence of up to 20 ng/μL non-target host gDNA using SYBR Green chemistry alone, or in the presence of up to 160 ng/μL host gDNA through the utilization of a TaqMan probe common-reporter detection system. These methods were subsequently used to positively identify both C. forsteri and C. orientalis DNA in preserved samples of serum, gill, and heart from ranched Southern Bluefin Tuna Thunnus maccoyii. Both methods were more sensitive for positively and differentially identifying the presence of Cardicola spp. than either histological or heart-flush microscopy techniques previously employed, and also possess the ability to be applied in non-lethal blood sampling of these highly valued fish. This is the first report for rapid and differential molecular quantitative detection of Cardicola, and opens the potential for effective monitoring of infection in cultured bluefin populations. Further, it is anticipated that the use of SYBR Green for melt-curve analyses in conjunction with a common-reporter TaqMan assay will present a flexible, accurate, and cost-effective approach for differential detection of a variety of other pathogens in future. PMID:23896120

  2. Alcoholic liver disease: The gut microbiome and liver crosstalk

    PubMed Central

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

  3. Liver regeneration following repeat SBRT

    PubMed Central

    Farach, Andrew; Quesada, Jorge

    2015-01-01

    Liver stereotactic body radiation therapy (SBRT) is an emerging treatment option for oligometastases and may confer a survival benefit in select patients. Herein, we document the first case of liver regeneration (LR) following repeat right hepatic lobe SBRT in a woman with breast cancer metastases. Retraction of the treated lobe was significant with a near 50% volume reduction. Compensatory contralateral lobe hypertrophy was noted with a 320% volume increase. The overall liver volume remained stable, within ±5% of baseline. This case indicates that repeat liver SBRT can be delivered safely to individual patients and that compensatory contralateral lobe hypertrophy is observed to maintain a functional liver volume. PMID:25830045

  4. Liver regeneration following repeat SBRT.

    PubMed

    Farach, Andrew; Quesada, Jorge; Teh, Bin S

    2015-04-01

    Liver stereotactic body radiation therapy (SBRT) is an emerging treatment option for oligometastases and may confer a survival benefit in select patients. Herein, we document the first case of liver regeneration (LR) following repeat right hepatic lobe SBRT in a woman with breast cancer metastases. Retraction of the treated lobe was significant with a near 50% volume reduction. Compensatory contralateral lobe hypertrophy was noted with a 320% volume increase. The overall liver volume remained stable, within ±5% of baseline. This case indicates that repeat liver SBRT can be delivered safely to individual patients and that compensatory contralateral lobe hypertrophy is observed to maintain a functional liver volume. PMID:25830045

  5. Liver Resection for Intrahepatic Stones

    PubMed Central

    Tranberg, Karl-Göran; Beng-Mark, Stig

    1990-01-01

    Intrahepatic stones are difficult to manage, especially when they are associated with bile duct stricture, cholangitis and destruction of liver parenchyma. Suggested modes of treatment include surgical bile duct exploration, endoscopic procedures, transhepatic cholangiolithotomy and liver resection. This paper reports 2 patients in whom liver resection was performed because of intrahepatic ductal stones, bile duct strictures and repeated episodes of cholangitis. Liver resection was uncomplicated and long-term results were satisfactory. Our results support the view that liver resection is indicated in rare instances of intrahepatic bile duct stones associated with bile duct strictures. PMID:2278909

  6. Epidemiology of cancer of the liver and intrahepatic bile ducts in an Australian population.

    PubMed

    Luke, Colin; Price, Timothy; Roder, David

    2010-01-01

    The incidence of liver and intrahepatic bile duct cancer in Australia is low at about one third the world average but increases are evident. South Australian registry data have been used to describe: age-standardized incidence and mortality trends; and disease-specific survivals, using Kaplan-Meier estimates and Cox proportional hazards regression. The study included 1,220 incident cancers (901 hepatocellular carcinomas; 201 cholangiocarcinomas; 118 other types) and 983 deaths. Incidence and mortality rates increased by 2-3 fold during 1977-2007. Incidence increases affected males, females and all ages. There was a strong: male predominance (3 to 1); and age gradient (70+ year old incidence >30 times under 50 year old incidence). Compared with hepatocellular carcinomas, cholangiocarcinomas and other histology types more often affected females and older ages and less often the Asian born. All histology types showed similar incidence increases. Apart from recognized risk factors (e.g., hepatitis B/C infection and aflatoxins for hepatocellular carcinoma; liver-fluke infection for cholangiocarcinomas, etc.), common risk factors may include excess alcohol consumption and possibly obesity and diabetes mellitus. Five-year disease-specific survival in 1998-2007 was 16%, with higher fatalities applying for earlier periods, older patients, males, lower socio-economic groups, and cholangiocarcinomas. Aboriginal patients tended to have higher case fatalities (p=0.054). Survival increases may be due to earlier diagnosis from alpha feta protein testing and diagnostic imaging, plus more aggressive treatment of localized disease. Mortality increases require a preventive response, including hepatitis B vaccination, prevention of viral infection though contaminated blood and other body fluids, early detection initiatives for high-risk patients, aggressive surgery for localized disease, and experimentation with new systemic therapies. PMID:21338184

  7. Drug-induced Liver Injury

    PubMed Central

    David, Stefan; Hamilton, James P

    2011-01-01

    Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. PMID:21874146

  8. Liver transplantation for hepatocellular carcinoma

    PubMed Central

    Tanwar, Sudeep; Khan, Shahid A; Grover, Vijay Paul Bob; Gwilt, Catherine; Smith, Belinda; Brown, Ashley

    2009-01-01

    Hepatocellular carcinoma (HCC) is the commonest primary malignancy of the liver. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Orthotopic liver transplantation (OLT) is a suitable therapeutic option for early, unresectable HCC particularly in the setting of chronic liver disease. Following on from disappointing initial results, the seminal study by Mazzaferro et al in 1996 established OLT as a viable treatment for HCC. In this study, the “Milan criteria” were applied achieving a 4-year survival rate similar to OLT for benign disease. Since then various groups have attempted to expand these criteria whilst maintaining long term survival rates. The technique of living donor liver transplantation has evolved over the past decade, particularly in Asia, and published outcome data is comparable to that of OLT. This article will review the evidence, indications, and the future direction of liver transplantation for liver cancer. PMID:19938188

  9. Liver scintigraphy in ponies

    SciTech Connect

    Theodorakis, M.C.; Bermudez, A.J.; Manning, J.P.; Koritz, G.D.; Hillidge, C.J.

    1982-09-01

    Six derivatives of ethylenediamine-N,N'-bis (alpha-2-hydroxy phenyl) acetic acid labeled with /sup 99m/Tc were prepared and their imaging qualities evaluated in ponies. The 6 agents produced good scintigraphic images of certain structures of the liver in the pony. For each agent, 13 different scans were taken. Dorsal views of the left lateral, right lateral, and quadrate lobe were obtained with dorsal scans. Left lateral and left lateral oblique (45 degrees) scans provided a left lateral view of the left lobe and a medial view of the right lateral lobe. Right lateral scans revealed the right lateral and quadrate lobes. Administration of /sup 99m/Tc-labeled colloids which are commonly used in other species for liver scintigraphy resulted in extensive lung uptake in the pony.

  10. Fatty liver in childhood

    PubMed Central

    Ozturk, Yesim; Soylu, Ozlem Bekem

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease (NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today. PMID:24653792

  11. Liver transplantation and non-alcoholic fatty liver disease

    PubMed Central

    Zezos, Petros; Renner, Eberhard L

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis (nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance (or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following: (1) the increasing need for liver transplantation due to NASH; (2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation; (3) the long term graft and patient outcomes after liver transplantation for NASH, and finally; and (4) the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes. PMID:25400437

  12. Laparoscopic anatomic liver resection

    PubMed Central

    Vibert, Eric; Kouider, Ali

    2004-01-01

    Background Liver resection is reputed to be one of the most difficult procedures embraced in laparoscopy. This report shows that with adequate training, anatomical liver resection including major hepatectomies can be performed. Methods This is a retrospective study. Results From 1995 to 2004, among 84 laparoscopic liver resections, 46 (54%) anatomical laparoscopic hepatectomies were performed in our institution by laparoscopy. Nine (20%) patients had benign disease while 37 (80%) had malignant lesions. Among those with malignant lesions, 14 patients had hepatocellular carcinoma (HCC), 18 had colorectal metastasis (CRM), while 5 had miscellaneous tumours. For benign disease, minor (two Couinaud's segments or less) and major anatomic hepatectomies were performed in five and four patients, respectively. For malignant lesions, minor and major anatomic hepatectomies were performed in 15 and 22 patients, respectively. Overall, conversion to laparotomy was necessary in 7 (15%) patients. Blood transfusion was required in five (10%) patients. One patient died of cerebral infarction 8 days after a massive peroperative haemorrhage. The overall morbidity rate was 34% whatever the type of resection. Three patients required reoperation, either for haemorrhage (n=1) and/or biliary leak (n=2). For CRM (n=18), overall and disease-free survival at 24 months (mean follow-up of 17 months) were 100% and 56%, respectively. For HCC (n=14), overall and disease-free survival at 36 months (mean follow-up of 29 months) were 91% and 65%, respectively. No port site metastasis occurred in patients with malignancy. Conclusions After a long training with limited liver resection in superficial segments, laparoscopic anatomical minor and major resections are feasible. Short-term carcinological results seem to be similar to those obtained with laparotomy. PMID:18333079

  13. Iron and the liver.

    PubMed

    Pietrangelo, Antonello

    2016-01-01

    Humans have evolved to retain iron in the body and are exposed to a high risk of iron overload and iron-related toxicity. Excess iron in the blood, in the absence of increased erythropoietic needs, can saturate the buffering capacity of serum transferrin and result in non-transferrin-bound highly reactive forms of iron that can cause damage, as well as promote fibrogenesis and carcinogenesis in the parenchymatous organs. A number of hereditary or acquired diseases are associated with systemic or local iron deposition or iron misdistribution in organs or cells. Two of these, the HFE- and non-HFE hemochromatosis syndromes represent the paradigms of genetic iron overload. They share common clinical features and the same pathogenic basis, in particular, a lack of synthesis or activity of hepcidin, the iron hormone. Before hepcidin was discovered, the liver was simply regarded as the main site of iron storage and, as such, the main target of iron toxicity. Now, as the main source of hepcidin, it appears that the loss of the hepcidin-producing liver mass or genetic and acquired factors that repress hepcidin synthesis in the liver may also lead to iron overload. Usually, there is low-grade excess iron which, through oxidative stress, is sufficient to worsen the course of the underlying liver disease or other chronic diseases that are apparently unrelated to iron, such as chronic metabolic and cardiovascular diseases. In the future, modulation of hepcidin synthesis and activity or hepcidin hormone-replacing strategies may become therapeutic options to cure iron-related disorders. PMID:26725908

  14. Colorectal liver metastases.

    PubMed Central

    Burke, D.; Allen-Mersh, T. G.

    1996-01-01

    Each year in the UK, between 12-14,000 people develop liver metastases from colorectal cancer. These metastases will contribute to the death of the patient in about 80% of cases. Treatments aimed at these tumours are best administered when the tumour is small. Current investigative methods allow tumours as small as 0.5 mm to be detected, and should be offered to all colorectal cancer patients at risk of developing liver metastases. Surgery remains the only curative treatment for these tumours, but, unfortunately, only 20% of those who have tumour excision will survive five years. In those patients unsuitable for surgery, chemotherapy with fluoropyrimidines produces the best tumour response. This may be administered systemically or regionally, via a catheter placed within the hepatic artery. The latter approach reduces systemic toxicity, but may produce hepatotoxicity. The results of other forms of systemic chemotherapy currently undergoing clinical trials are awaited. The vast majority of patients will benefit from suitable palliative treatment delivered either locally or systemically. With the wide range of treatments now available for liver metastases, these patients are best assessed in a unit with a special interest in the problem. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8796208

  15. Voriconazole and the liver

    PubMed Central

    Mihăilă, Romeo-Gabriel

    2015-01-01

    Voriconazole is an azole useful for the prophylaxis and the treatment of aspergillosis and other fungal infections in immunosuppressed subjects, as those found in aplasia after aggressive polychemotherapy treatments, after hematopoietic stem cell, liver or lung transplantation. Its administration in therapeutic doses lead to extremely varied serum levels from patient to patient and even to the same patient. The explanations are varied: nonlinear pharmacokinetics, certain patient-related factors, including genetic polymorphisms in the cytochrome P450 2C19 gene, the kidney and liver function, simultaneous administration with other drugs metabolised by the same cytochrome. It is recommended to maintain the serum concentrations of voriconazole between 1.5 and 4 μg/mL. At lower values its efficacy decreases and at higher values the risk of neurological toxicity increases. Even at these concentrations it is not excluded the possible appearance of a variety of toxic effects, including on the liver, manifested by cholestasis, hepatocytolisis, or their combination. It is recommended to monitor the clinical and laboratory evolution of all patients treated with voriconazole, and of the serum levels of the drug of those who belong to risk groups, even if there is still no consensus on this issue, given the lack of correlation between the serum level and the occurrence of adverse effects in many patients. PMID:26207164

  16. [Bleeding problems in liver surgery and liver transplantation].

    PubMed

    Bechstein, W O; Neuhaus, P

    2000-04-01

    In liver resection, severe bleeding can be prevented by appropriate surgical techniques. These include adequate access and mobilisation, vascular occlusion, controlled dissection of the parenchyma, prevention of venous "over-filling" and secure hemostasis of the resection surface. Excessive bleeding, both in liver resection and liver transplantation, poses a major risk for the development of postoperative complications. In liver transplantation the surgeon is most often confronted with patients with chronic liver disease and portal hypertension. Coagulation disorders are the rule, and the surgery itself is more demanding because of fragile venous collaterals as a consequence of portal hypertension. With the use of extracorporeal venovenous bypass or newer techniques with preservation of the vena cava, some of these difficulties can be overcome. Pharmacological therapies like administration of aprotinin can reduce the fibrinolysis inherent in liver transplantation. However, surgical skill and experience are probably still the most important predictors of blood loss during surgery. PMID:10840602

  17. Protective effect of melatonin against Opisthorchis viverrini-induced oxidative and nitrosative DNA damage and liver injury in hamsters.

    PubMed

    Laothong, Umawadee; Pinlaor, Porntip; Hiraku, Yusuke; Boonsiri, Patcharee; Prakobwong, Suksanti; Khoontawad, Jarinya; Pinlaor, Somchai

    2010-10-01

    The liver fluke, Opisthorchis viverrini, is the risk factor of cholangiocarcinoma, which is a major health problem in northeastern Thailand. Production of reactive oxygen and nitrogen species during the host's response leads to oxidative and nitrosative stress contributing to carcinogenesis. We investigated the protective effect of melatonin against O. viverrini-induced oxidative and nitrosative stress and liver injury. Hamsters were infected with O. viverrini followed by oral administration of various doses of melatonin (5, 10, and 20 mg/kg body weight) for 30 days. Uninfected hamsters served as controls. Compared to the levels in O. viverrini-infected hamsters without melatonin treatment, the indoleamine decreased the formation of oxidative and nitrosative DNA lesions, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-nitroguanine, in the nucleus of bile duct epithelium and inflammatory cells, in parallel with a reduction in 3-nitrotyrosine. Melatonin also reduced the expression of heme oxygenase-1 and cytokeratin 19, nitrate/nitrite levels, and bile duct proliferation in the liver. Alanine transaminase activity and the levels of 8-isoprostane and vitamin E were also dose dependently decreased in the plasma of melatonin-treated hamsters. Melatonin reduced the mRNA expression of oxidant-generating genes [inducible nitric oxide synthase, nuclear factor-kappa B (NF-κB), and cyclooxygenase-2] and proinflammatory cytokines (TNF-α and IL-1β), accompanied by an increase in the expression of antioxidant genes [nuclear erythroid 2-related factor 2 (Nrf2) and manganese superoxide dismutase]. Thus, melatonin may be an effective chemopreventive agent against O. viverrini-induced cholangiocarcinoma by reducing oxidative and nitrosative DNA damage via induction of Nrf2 and inhibition of NF-κB-mediated pathways. PMID:20626588

  18. Role of liver progenitors in acute liver injury

    PubMed Central

    Best, Jan; Dollé, Laurent; Manka, Paul; Coombes, Jason; van Grunsven, Leo A.; Syn, Wing-Kin

    2013-01-01

    Acute liver failure (ALF) results from the acute and rapid loss of hepatocyte function and frequently exhibits a fulminant course, characterized by high mortality in the absence of immediate state-of-the-art intensive care and/or emergency liver transplantation (ELT). The role of hepatocyte-mediated liver regeneration during acute and chronic liver injury has been extensively investigated, and recent studies suggest that hepatocytes are not exclusively responsible for the regeneration of the injured liver during fulminant liver injury. Liver progenitor cells (LPC) (or resident liver stem cells) are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. This review aims to provide an overview of the role of the LPC population during ALF, and the role of putative cytokines, growth factors, mitogens, and hormones in the LPC response. We will highlight the potential interaction among cellular compartments during ALF, and discuss the possible prognostic value of the LPC response on ALF outcomes. PMID:24133449

  19. Liver transplantation in acute liver failure: A challenging scenario

    PubMed Central

    Mendizabal, Manuel; Silva, Marcelo Oscar

    2016-01-01

    Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation. PMID:26819519

  20. Pregnancy-Related Liver Disorders

    PubMed Central

    Goel, Ashish; Jamwal, Kapil D.; Ramachandran, Anup; Balasubramanian, Kunissery A.; Eapen, Chundamannil E.

    2013-01-01

    Pregnancy-related liver disorders accounted for 8% of all maternal deaths at our center from 1999 to 2011. Of the three pregnancy-related liver disorders (acute fatty liver of pregnancy (AFLP), HELLP (Hemolysis, elevated liver enzymes, low platelets) syndrome and pre-eclamptic liver dysfunction, which can lead to adverse maternal and fetal outcome, AFLP is most typically under - diagnosed. Risk of maternal death can be minimised by timely recognition and early/aggressive multi-specialty management of these conditions. Urgent termination of pregnancy remains the cornerstone of therapy for some of these life threatening disorders, but recent advancements in our understanding help us in better overall management of these patients. This review focuses on various aspects of pregnancy-related liver disorders. PMID:25755551

  1. Experimental models of liver fibrosis

    PubMed Central

    Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2015-01-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research. PMID:26047667

  2. Experimental models of liver fibrosis.

    PubMed

    Crespo Yanguas, Sara; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research. PMID:26047667

  3. Obesity, Inflammation and Liver Cancer

    PubMed Central

    Sun, Beicheng; Karin, Michael

    2012-01-01

    Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact, due to its much higher prevalence, obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation, and their contribution to hepatocarcinogenesis. PMID:22120206

  4. Stem cells for liver regeneration.

    PubMed

    Than, N N; Newsome, P N

    2014-06-01

    The liver has a unique capacity to repair following injury, which is largely achieved by proliferation of hepatocytes. However, in situations of chronic or overwhelming liver injury, additional repair mechanisms, namely liver progenitor or oval cells, are activated. These cells, located in the canals of Hering, express markers for both hepatocytes and biliary cells and have the capacity to differentiate down both hepatocyte and biliary lineages. Previous work has suggested that the administration of autologous or allogeneic cell therapies such as haematopoietic or mesenchymal stem cells can augment liver repair by either stimulating endogenous repair mechanisms or by suppressing ongoing damage. A better understanding of how cell therapies can promote liver regeneration will lead to the refinement of these therapeutic approaches and also develop new pharmacological agents for liver repair. PMID:24453286

  5. Intestinal microbiota in liver disease.

    PubMed

    Haque, Tanvir R; Barritt, A Sidney

    2016-02-01

    The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation. PMID:27048904

  6. Folate, Alcohol, and Liver Disease

    PubMed Central

    Medici, Valentina; Halsted, Charles H.

    2013-01-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

  7. Radiation-associated liver injury.

    PubMed

    Pan, Charlie C; Kavanagh, Brian D; Dawson, Laura A; Li, X Allen; Das, Shiva K; Miften, Moyed; Ten Haken, Randall K

    2010-03-01

    The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver. PMID:20171524

  8. Radiation-Associated Liver Injury

    SciTech Connect

    Pan, Charlie C.; Kavanagh, Brian D.; Dawson, Laura A.; Li, X. Allen; Das, Shiva K.; Miften, Moyed; Ten Haken, Randall K.

    2010-03-01

    The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver.

  9. Hepatic sarcoidosis mimicking liver cancer.

    PubMed

    Yu, Kang-Kang; Liu, Han-Qiu; Zhou, Zhong-Wen; Chen, Ming-Quan

    2015-01-01

    We present a case of a 50-year-old woman with multiple occupations in the liver. Liver cancer was strongly suspected initially according to the results of imaging examination. However, sarcoidosis was confirmed subsequently by liver biopsy, so methylprednisolone was then prescribed and the patient showed favorable therapeutic response. This case report suggests that hepatic mass in Chinese patients without any history of hepatitis virus infection should be carefully investigated before giving a diagnosis of liver cancer. The report also reminds us that the clinical presentation of sarcoidosis is complex and involvement of a single extra-pulmonary organ should not be ignored. PMID:26309634

  10. Iron homeostasis in the liver

    PubMed Central

    Anderson, Erik R; Shah, Yatrik M

    2014-01-01

    Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver which control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary causes of iron-related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver-derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely the heart and pancreas from iron-induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. PMID:23720289

  11. Blood flukes (Digenea: Aporocotylidae) of epipelagic lamniforms: redescription of Hyperandrotrema cetorhini from basking shark (Cetorhinus maximus) and description of a new congener from shortfin mako shark (Isurus oxyrinchus) off Alabama.

    PubMed

    Orélis-Ribeiro, Raphael; Ruiz, Carlos F; Curran, Stephen S; Bullard, Stephen A

    2013-10-01

    We emend the original generic diagnosis for Hyperandrotrema Maillard and Ktari, 1978 , and redescribe its type species Hyperandrotrema cetorhini Maillard and Ktari, 1978 (Digenea: Aporocotylidae Odhner, 1912), based on the holotype and 2 paratypes collected from the heart of basking shark (Cetorhinus maximus). We also describe Hyperandrotrema walterboegeri Orélis-Ribeiro and Bullard n. sp. based on light and scanning electron microscopy of 6 adult specimens collected from the heart of a shortfin mako shark (Isurus oxyrinchus Rafinesque, 1810) captured from Viosca Knoll (29°11.70'N, 88°33.32'W; 123 km southwest of Dauphin Island, Alabama), northern Gulf of Mexico. Hyperandrotrema spp. infect lamniforms and differ from all other nominal aporocotylids at least by having a ventrolateral field of robust C-shaped spines (rather than transverse rows of minute, shaft-like spines), an inverse U-shaped intestine with extremely elongate ceca terminating near the level of the excretory bladder, and a common genital pore that comprises the dorsal opening of a common genital atrium. Adults of the new species exceeded 12 mm in total length, making them the largest of the nominal fish blood flukes. The new species further differs from H. cetorhini by the combination of having an adult body that is 7-8 times longer than wide, large midbody tegumental spines measuring 25-38 μm long × 10-12 μm wide, a long vas deferens 4-5% of the body length, a testis 9-11 times longer than wide, and a large ootype 105-150 μm long × 85-105 μm wide. This is the first report of Hyperandrotrema from the Gulf of Mexico and the second aporocotylid species reported from an epipelagic elasmobranch. Our results demonstrate that ecologically related (epipelagic, marine) and phylogenetically related (Lamniformes) definitive hosts are infected by morphologically similar (congeneric) fish blood flukes. PMID:23597211

  12. Chronic liver inflammation: Clinical implications beyond alcoholic liver disease

    PubMed Central

    Park, Byoung-Jin; Lee, Yong-Jae; Lee, Hye-Ree

    2014-01-01

    Chronic alcohol exposure can lead to alcoholic liver disease, including hepatitis, cirrhosis and hepatocellular carcinoma, and chronic inflammation can simultaneously cause systemic medical illness. Recent evidence suggests that alcoholic liver disease is a predictor for liver-related diseases, cardiovascular disease, immunologic disease, and bone disease. Chronic inflammation in alcoholic liver disease is mediated by a direct inflammatory cascade from the alcohol detoxification process and an indirect inflammatory cascade in response to gut microflora-derived lipopolysaccharides (LPS). The pathophysiology of alcoholic liver disease and its related systemic illness is characterized by oxidative stress, activation of the immune cascade, and gut-liver interactions. Integrative therapeutic strategies for alcoholic liver disease include abstaining from alcohol consumption; general anti-inflammatories such as glucocorticoid, pentoxifylline, and tumour necrosis factor-α antagonist; antioxidants such as N- acetylcysteine; gut microflora and LPS modulators such as rifaximin and/or probiotics. This review focuses on the impact of chronic liver inflammation on systemic health problems and several potential therapeutic targets. PMID:24605015

  13. Study of the local immune response to Fasciola hepatica in the liver and hepatic lymph nodes of goats immunised with a peptide of the Sm14 antigen.

    PubMed

    Zafra, R; Buffoni, L; Pérez-Ecija, R A; Mendes, R E; Martínez-Moreno, A; Martínez-Moreno, F J; Pérez, J

    2009-10-01

    The nature of the local immune response was assessed studying the distribution of CD2(+), CD4(+), CD8(+), gammadelta(+) T lymphocytes, IgM(+) B cells, IL-4(+) and IFN-gamma(+) cells in the liver and hepatic lymph nodes (HLN) of goats immunised with a synthetic peptide of the Sm14 antigen from Schistosoma mansoni and challenged with Fasciola hepatica. A morphometric study of HLN was also carried out in order to evaluate the hyperplasia of lymphoid follicles. Despite the decrease in fluke burdens found in the immunised group (45.9%) respect to the infected control group, this difference was not statistically significant due to the high individual variability. In liver, a significant increase of CD2(+), CD4(+), CD8(+), gammadelta(+) T lymphocytes was found in the infected groups respect to the uninfected control and in the infected control respect to the immunised group. HLN showed a significant enlargement due to the hyperplasia of lymphoid follicles and infiltration of CD2(+), CD4(+), CD8(+), gammadelta(+) T lymphocytes in both infected groups respect to the uninfected control, with no significant differences between the infected control and immunised group. IFN-gamma(+) lymphoid cells was absent or very occasional in HLN where the number of IL-4(+) cells was higher than that of IFN-gamma, suggesting a polarized Th2 response in immunised and in infected control group. PMID:19345386

  14. Lipotoxicity in the liver

    PubMed Central

    Zámbó, Veronika; Simon-Szabó, Laura; Szelényi, Péter; Kereszturi, Éva; Bánhegyi, Gábor; Csala, Miklós

    2013-01-01

    Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21st century. With the increasing prevalence of obesity, non-alcoholic fatty liver disease is also emerging as a pandemic. While previously this pathophysiological condition was mainly attributed to triglyceride accumulation in hepatocytes, recent data show that the development of oxidative stress, lipid peroxidation, cell death, inflammation and fibrosis are mostly due to accumulation of fatty acids, and the altered composition of membrane phospholipids. In fact, triglyceride accumulation might play a protective role, and the higher toxicity of saturated or trans fatty acids seems to be the consequence of a blockade in triglyceride synthesis. Increased membrane saturation can profoundly disturb cellular homeostasis by impairing the function of membrane receptors, channels and transporters. However, it also induces endoplasmic reticulum stress via novel sensing mechanisms of the organelle’s stress receptors. The triggered signaling pathways in turn largely contribute to the development of insulin resistance and apoptosis. These findings have substantiated the lipotoxic liver injury hypothesis for the pathomechanism of hepatosteatosis. This minireview focuses on the metabolic and redox aspects of lipotoxicity and lipoapoptosis, with special regards on the involvement of endoplasmic reticulum stress responses. PMID:24179614

  15. Therapy of Liver Abscesses

    PubMed Central

    Lbbert, Christoph; Wiegand, Johannes; Karlas, Thomas

    2014-01-01

    Summary Background Liver abscess (LA) is an uncommon but potentially life-threatening disease with significant morbidity and mortality. Methods This review comprehensively describes epidemiology, pathogenesis, diagnosis, and treatment of LA, with a strong focus on antimicrobial treatment choices and the impact of multidrug-resistant pathogens. Results In industrialized areas, pyogenic liver abscess (PLA) accounts for over 80% of the cases, whereas Entamoeba histolyticais responsible for up to 10% of the cases, with a higher incidence in tropical areas. Highly virulent strains of Klebsiella pneumoniaehave emerged as a predominant cause of PLA in Asian countries and tend to spread to the USA, Australia, and European countries, therefore requiring special alertness. Most common symptoms of LA are fever, chills, and right upper quadrant abdominal pain, although a broad spectrum of non-specific symptoms may also occur. Conclusion Imaging studies (ultrasound, computed tomography scan) and microbiological findings play a crucial role in the diagnosis of LA. The treatment of choice for PLA is a multimodal approach combining broad-spectrum antibiotics and aspiration or drainage of larger abscess cavities. Amebic LA can be cured by metronidazole therapy without drainage. PMID:26287275

  16. Liver Cancer: Connections with Obesity, Fatty Liver, and Cirrhosis.

    PubMed

    Marengo, Andrea; Rosso, Chiara; Bugianesi, Elisabetta

    2016-01-14

    The burden of hepatocellular carcinoma (HCC), the most common form of liver cancer, is steadily growing because obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) are replacing viral- and alcohol-related liver disease as major pathogenic promoters. The most worrisome aspects of these new risk factors are their large spread in the general population and their link with HCC arising in noncirrhotic livers. HCC may be the presenting feature of an asymptomatic nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. The HCC risk connected to metabolic factors has been underestimated so far, and a poorer surveillance has prevented an adequate treatment. Systemic and hepatic molecular mechanisms involved in obesity- and NAFLD-induced hepatocarcinogenesis as well as potential early markers of HCC are being extensively investigated. This review summarizes current evidence linking obesity, NAFLD and liver cancer, discusses its clinical impact and describes the main mechanisms underlying this complex relationship. PMID:26473416

  17. Fulminant zygomycosis of graft liver following liver transplantation.

    PubMed

    Sethi, Pulkit; Balakrishnan, Dinesh; Surendran, Sudhindran; Mohamed, Zubair Umer

    2016-01-01

    A 44-year-old man with hepatitis B virus (HBV)-related cirrhosis underwent living donor liver transplantation at our institute. Induction of immunosuppression was achieved with basiliximab, due to deranged renal function, and maintained with prednisolone, tacrolimus and mycophenolate mofetil. The intraoperative and immediate postoperative periods were fairly uneventful. A duplex scan, taken during the third week post-transplantation due to sudden rise in liver enzymes, revealed multifocal hypoechoic lesions in the graft liver with normal Doppler parameters. Multidetecor computed tomography (MDCT) showed multiple hypodense vessel-sparing lesions in the graft liver. Cultures from the aspirate grew filamentous fungi identified as Basidiobolus ranarum species. Despite multiple broad spectrum antifungal infusions including liposomal amphotericin, itraconazole, caspofungin and posaconazole, serial sonography showed the hepatic lesions increasing in size, and involving segments V, VI and VII. The patient developed severe liver dysfunction ultimately progressing to sepsis, multiorgan dysfunction and death. PMID:26873918

  18. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  19. Primary Neuroendocrine Tumor of Liver (Rare Tumor of Liver)

    PubMed Central

    Mousavi, Seyed Reza; Ahadi, Mahsa

    2015-01-01

    Introduction: A neuroendocrine tumor has known as a neuroendocrine system tumor. Rarely, neuroendocrines have found in other areas, like the liver, gallbladder, bile ducts, kidneys, ovaries or testicles. Case Presentation: We have a 41-year-old woman has referred to our medical center, complaining of fullness and vague pain on her right upper quadrant. The liver scan, sonography, MRI demonstrated multi lobular cysts in 6th and 7 th seg-ments of her liver and chest imaging was normal, oc-terotid scan has not shwon metastatic neuroendocrine tour of liver. Conclusions: Liver could be the location of metastatic neuroendo-crine tumors, for example metastatic carcinoid tumor. Therefore, it was so important to diffrentatiate pri-mary neuroendocrine tumor from metastatic neuro-endocrine tumors. PMID:26855717

  20. Clonorchiasis.

    PubMed

    Qian, Men-Bao; Utzinger, Jürg; Keiser, Jennifer; Zhou, Xiao-Nong

    2016-02-20

    On Aug 21, 1875, James McConnell published in The Lancet his findings from a post-mortem examination of a 20-year-old Chinese man--undertaken at the Medical College Hospital in Calcutta, India--in whom he found Clonorchis sinensis in the bile ducts. Now, exactly 140 years later, we have a sound understanding of the lifecycle of this liver fluke, including key clinical, diagnostic, and epidemiological features. Developments in the so-called -omics sciences have not only advanced our knowledge of the biology and pathology of the parasite, but also led to the discovery of new diagnostic, drug, and vaccine targets. C sinensis infection is primarily related to liver and biliary disorders, especially cholangiocarcinoma. Clonorchiasis mainly occurs in east Asia, as a result of the region's social-ecological systems and deeply rooted cultural habit of consuming raw freshwater fish. The Kato-Katz technique, applied on fresh stool samples, is the most widely used diagnostic approach. Praziquantel is the treatment of choice and has been considered for preventive chemotherapy. Tribendimidine showed good safety and therapeutic profiles in phase 2 trials and warrants further investigation. Still today, the precise distribution, the exact number of infected people, subtle morbidities and pathogenesis, and the global burden of clonorchiasis are unknown. Integrated control strategies, consisting of preventive chemotherapy; information, education, and communication; environmental management; and capacity building through intersectoral collaboration should be advocated. PMID:26299184

  1. Therapeutic liver repopulation for phenylketonuria.

    PubMed

    Harding, Cary O; Gibson, K M

    2010-12-01

    Problems with long-term dietary compliance in phenylketonuria (PKU) necessitate the development of alternative treatment approaches. Therapeutic liver repopulation with phenylalanine hydroxylase (PAH)-expressing cells following hepatocyte or haematopoietic stem cell transplantation has been investigated as a possible novel treatment approach for PKU. Successful therapeutic liver repopulation requires both a stimulus for liver regeneration at the time of cell transplantation and a selective growth advantage for the PAH+ donor cells. Unfortunately, wild-type PAH+ hepatocytes do not enjoy any growth advantage over PAH- cells. Successful correction of hyperphenylalaninemia following therapeutic liver repopulation has been accomplished only in an animal model that yields a selective advantage for the donor cells. Haematopoietic stem cell (HSC)-mediated therapeutic liver repopulation has not been reported in any hyperphenylalaninemic system, and the success of HSC-mediated liver repopulation for PKU may be limited by the slow kinetics of this approach. If therapeutic liver repopulation is to be employed successfully in humans with PKU, an effective method of providing a selective growth advantage for the donor cells must be developed. If this can be achieved, liver repopulation with 10-20% wild-type hepatocytes will likely completely normalize Phe clearance in individuals with PKU. PMID:20495959

  2. The Liver, Regulator of Nutrition.

    ERIC Educational Resources Information Center

    Dillon, J. C.

    1995-01-01

    The purpose of this theme issue is to review the basic physiological, nutritional, and pathological facts pertaining to the liver. It is an educational tool through which university teachers and people in charge of training may enhance their teaching programs. The main liver diseases seen in young children and pregnant women in tropical regions is…

  3. Current Issues in Liver Transplantation

    PubMed Central

    2016-01-01

    The state of liver transplantation continues to evolve. This article focuses on 3 separate yet important issues within this field. First, there is a proposal to change the allocation of donor livers in the United States. The fundamental premise of this proposal is to equalize access to donor livers across the country. To accomplish this goal, the proposal is to increase the geographic area of liver allocation. As might be expected, there is a great deal of controversy surrounding the possibility of a major change in liver allocation and distribution. A second area of interest, and perhaps the most important therapeutic breakthrough in the field of hepatology, is the introduction of direct-acting antiviral agents against hepatitis C virus (HCV) infection. With cure rates up to 100%, an increasing proportion of liver transplant candidates and recipients are being cured of HCV infection with therapies that have minimal side effects. Consequently, the impact of HCV infection on patient and graft survival will likely improve substantially over the next few years. Finally, this article reviews the role of donor-specific antibodies (DSAs) in antibody-mediated rejection. Long recognized as an important factor in graft survival in renal transplantation, DSAs have recently been shown to be a strong predictor of graft and patient survival in liver transplantation. However, the importance of DSAs in liver transplantation is uncertain, in large part due to the absence of proven therapies. PMID:27231452

  4. LIVER AND THE METABOLIC SYNDROME

    EPA Science Inventory

    We have developed the following specific aims: Specific Aim 1 will be to develop a model and the liver phenotype (defined as above) is maintained. In Specific Aim 2, we will demonstrate that manipulation of the host environment will induce changes in liver tissues. We will exa...

  5. Percutaneous Cryoablation for Liver Cancer

    PubMed Central

    Niu, Li-Zhi; Li, Jia-Liang; Xu, Ke-Cheng

    2014-01-01

    Based on the primary tumor site, liver cancer can be divided into two categories: (1) primary liver cancer and (2) metastatic cancer to the liver from a distant primary site. Guided cryoablation via many imaging methods induces iceball formation and tumor necrosisand is an attractive option for treating unresectable hepatocellular carcinoma (HCC) and metastatic liver cancer. There are several advantages to using cryoablation for the treatment of liver cancer: it can be performed percutaneously, intraoperatively, and laparoscopically; iceball formation can be monitored; it has little impact on nearby large blood vessels; and it induces a cryo-immunological response in situ. Clinically, primary research has shown that percutaneous cryoablation of liver cancer is relatively safe and efficient, and it can be combined with other methods, such as radiation therapy, chemotherapy, and immunology, to control disease. Although research is preliminary, cryosurgery is fast becoming an alternative treatment method for HCC or liver tumors. Here, we review the mechanisms of liver tumor cryoablation, cryoablation program selection, clinical efficiency, and complications following treatment. PMID:26355719

  6. Chronic Liver Disease and African Americans

    MedlinePlus

    ... American > Chronic Liver Disease Chronic Liver Disease and African Americans Among African Americans, chronic liver disease is a ... white women. At a glance – Cancer Rates for African Americans (2008-2012) Cancer Incidence Rates per 100,000 – ...

  7. Evaluation of abnormal liver function tests.

    PubMed

    Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

    2016-04-01

    Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. PMID:26842972

  8. Liver Antigen-Presenting Cells

    PubMed Central

    Crispe, Ian Nicholas

    2010-01-01

    The liver is an organ is which several major pathogens evade immune clearance, and achieve chronicity. How do they do it? Recent research has documented multiple mechanisms by which immune responses in the liver are biased towards tolerance. In this review, the induction of local, intrahepatic tolerance is explored from the perspective of antigen presentation. Experiments support the role of liver Dendritic Cell subsets, but also of diverse subsets of unconventional antigen-presenting cells, in inducing immune suppression. The literature on this topic is controversial and sometimes contradictory, making it difficult to formulate a unified model of antigen handling and T cell priming in liver. Here I offer a critical review of the state of the art in understanding antigen presentation in the liver. PMID:21084131

  9. Fasciola hepatica: the flukicidal effect of some anaesthetics and analgesics in common use.

    PubMed

    Burden, D J; Hammet, N C

    1983-09-01

    The anaesthetic halothane and the sedative xylazine were shown to have anthelmintic properties in rats against the liver fluke Fasciola hepatica. Flukes in rats treated with the local anaesthetic lignocaine or the anaesthetic/analgesic ketamine were unaffected. PMID:6635348

  10. Orthotopic liver transplantation for giant liver haemangioma: A case report

    PubMed Central

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-01-01

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient’s renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient’s lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network “Eurotransplant”. The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  11. Ryanodine receptors in liver.

    PubMed

    Pierobon, Nicola; Renard-Rooney, Dominique C; Gaspers, Lawrence D; Thomas, Andrew P

    2006-11-10

    The ryanodine receptor has been mainly regarded as the Ca2+ release channel from sarcoplasmic reticulum controlling skeletal and cardiac muscle contraction. However, many studies have shown that it is widely expressed, with functions not restricted to muscular contraction. This study examined whether ryanodine receptor plays a role in calcium signaling in the liver. RT-PCR analysis of isolated hepatocytes showed expression of a truncated type 1 ryanodine receptor, but no type 2 or type 3 message was detected. We also detected binding sites for [3H]ryanodine in the microsomal cellular fraction and in permeabilized hepatocytes. This binding was displaced by caffeine and dantrolene, but not by ruthenium red, heparin or cyclic ADP-Ribose. Ryanodine, by itself, did not trigger Ca2+ oscillations in either primary cultured hepatocytes or hepatocytes within the intact perfused rat liver. In both preparations, however, ryanodine significantly increased the frequency of the cytosolic free [Ca2+] oscillations evoked by an alpha1 adrenergic receptor agonist. Experiments in permeabilized hepatocytes showed that both ryanodine and cyclic ADP-ribose evoked a slow Ca2+ leak from intracellular stores and were able to increase the Ca2+-released response to a subthreshold dose of inositol 1,4,5-trisphosphate. Our findings suggest the presence of a novel truncated form of the type 1 ryanodine receptor in rat hepatocytes. Ryanodine modulates the pattern of cytosolic free [Ca2+] oscillations by increasing oscillation frequency. We propose that the Ca2+ released from ryanodine receptors on the endoplasmic reticulum provides an increased pool of Ca2+ for positive feedback on inositol 1,4,5-trisphosphate receptors. PMID:16973607

  12. Extracorporeal Liver Support and Liver Transplant for Patients with Acute-on-Chronic Liver Failure.

    PubMed

    Li, Han; Chen, Harvey Shi-Hsien; Nyberg, Scott L

    2016-05-01

    Recognition of acute-on-chronic liver failure (ACLF) as a unique entity is slowly evolving, as are therapies to improve survival of affected patients. Further investigation into its disease process and proper treatments with critical timing are important for improving patient survival. At this time, liver transplant is the only treatment known to improve survival in liver-failure patients. However, liver transplantation has its own disadvantages, such as organ shortage and the need for lifelong immunotherapy. Bridging therapies such as extracorporeal liver-support systems are attractive options to stabilize patients until transplantation or spontaneous recovery. The goals of these liver-support systems are to remove detoxification products, reduce systemic inflammation, and enhance regeneration of the injured liver. These devices have been under development for the past decade; a few are in clinical trials. At this time, there is no proven clearcut survival benefit in these devices, but they may improve the outcome of challenging cases and potentially avoid or postpone liver transplantation in some cases. PMID:27172357

  13. Liver disease in cystic fibrosis

    PubMed Central

    Klincewicz, Beata; Cichy, Wojciech

    2014-01-01

    Cystic fibrosis-associated liver disease (CFLD) affects ca. 30% of patients. The CFLD is now considered the third cause of death, after lung disease and transplantation complications, in CF patients. Diagnostics, clinical assessment and treatment of CFLD have become a real challenge since a striking increase of life expectancy in CF patients has recently been observed. There is no elaborated “gold standard” in the diagnostic process of CFLD; clinical evaluation, laboratory tests, ultrasonography and liver biopsy are used. Clinical forms of CFLD are elevation of serum liver enzymes, hepatic steatosis, focal biliary cirrhosis, multilobular biliary cirrhosis, neonatal cholestasis, cholelithiasis, cholecystitis and micro-gallbladder. In children, CFLD symptoms mostly occur in puberty. Clinical symptoms appear late, when damage of the hepatobiliary system is already advanced. The CFLD is more common in patients with severe mutations of CFTR gene, in whom a complete loss of CFTR protein function is observed. CFLD, together with exocrine pancreatic insufficiency and meconium ileus, is considered a component of the severe CF phenotype. Treatment of CFLD should be complex and conducted by a multispecialist team (gastroenterologist, hepatologist, dietician, radiologist, surgeon). The main aim of the treatment is to prevent liver damage and complications associated with portal hypertension and liver cirrhosis. Ursodeoxycholic acid is used in the treatment of CFLD. There is no treatment of proven long-term efficacy in CFLD. Liver transplantation is a treatment of choice in end-stage liver disease. PMID:25097709

  14. Extracellular Matrix and Liver Disease

    PubMed Central

    Arriazu, Elena; Ruiz de Galarreta, Marina; Cubero, Francisco Javier; Varela-Rey, Marta; Pérez de Obanos, María Pilar; Leung, Tung Ming; Lopategi, Aritz; Benedicto, Aitor; Abraham-Enachescu, Ioana

    2014-01-01

    Abstract Significance: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. Critical Issues: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. Recent Advances: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF’ apoptosis, senescence, and reversal to quiescence. Future Directions: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new “omics” tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. Antioxid. Redox Signal. 21, 1078–1097. PMID:24219114

  15. Telocytes in human liver fibrosis

    PubMed Central

    Fu, Siyi; Wang, Fei; Cao, Yan; Huang, Qi; Xiao, Junjie; Yang, Changqing; Popescu, Laurentiu M

    2015-01-01

    Liver fibrosis is a wound-healing response which engages a variety of cell types to encapsulate injury. Telocyte (TC), a novel type of interstitial cell, has been identified in a variety of tissues and organs including liver. TCs have been reported to be reduced in fibrotic areas after myocardial infarction, human interstitial wall's fibrotic remodelling caused either by ulcerative colitis or Crohn's disease, and skin of systemic sclerosis. However, the role of TCs in human liver fibrosis remains unclear. Liver samples from human liver biopsy were collected. All samples were stained with Masson's trichrome to determine fibrosis. TCs were identified by several immunofluorescence stainings including double labelling for CD34 and c-kit/CD117, or vimentin, or PDGF Receptor-?, or ?. We found that hepatic TCs were significantly decreased by 27%60% in human liver fibrosis, suggesting that loss of TCs might lead to the altered organization of extracellular matrix and loss the control of fibroblast/myofibroblast activity and favour the genesis of fibrosis. Adding TCs might help to develop effective and targeted antifibrotic therapies for human liver fibrosis. PMID:25661250

  16. Arrhythmia risk in liver cirrhosis

    PubMed Central

    Mozos, Ioana

    2015-01-01

    Interactions between the functioning of the heart and the liver have been described, with heart diseases affecting the liver, liver diseases affecting the heart, and conditions that simultaneously affect both. The heart is one of the most adversely affected organs in patients with liver cirrhosis. For example, arrhythmias and electrocardiographic changes are observed in patients with liver cirrhosis. The risk for arrhythmia is influenced by factors such as cirrhotic cardiomyopathy, cardiac ion channel remodeling, electrolyte imbalances, impaired autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age, inflammatory syndrome, stressful events, impaired drug metabolism and comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias, particularly when QT interval-prolonging drugs are given, or if electrolyte imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after liver transplantation due to possible QT interval prolongation, persistence of the parasympathetic impairment, post-transplant reperfusion and chronic immunosuppression, as well as consideration of the fact that the transplant itself is a stressful event for the cardiovascular system. The aims of the present article were to provide a review of the most important data regarding the epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with liver cirrhosis, to elucidate the association with long-term outcome, and to propose future research directions. PMID:25866603

  17. Cellular Therapy for Liver Disease

    PubMed Central

    Huebert, Robert C.; Rakela, Jorge

    2014-01-01

    Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow–derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow–derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease. PMID:24582199

  18. Liver Transplantation: East versus West

    PubMed Central

    Shukla, Akash; Vadeyar, Hemant; Rela, Mohamed; Shah, Samir

    2013-01-01

    Liver transplantation (LT) has evolved rapidly since the first successful liver transplant performed in1967. Despite a humble beginning, this procedure gained widespread acceptance in the western world as a suitable option for patients with end stage liver disease (ESLD) by the beginning of the 1980s. At present, approximately 25,000 liver transplants are being performed worldwide every year with approximately 90% one year survival. The techniques of living donor liver transplantation (LDLT) developed in East Asia in the 1990s to overcome the shortage of suitable grafts for children and scarcity of deceased donors. While deceased donor liver transplantation (DDLT) constitutes more than 90% of LT in the western world, in India and other Asian countries, most transplants are LDLT. Despite the initial disparity, outcomes following LDLT in eastern countries have been quite satisfactory when compared to the western programs. The etiologies of liver failure requiring LT vary in different parts of the world. The commonest etiology for acute liver failure (ALF) leading to LT is drugs in the west and acute viral hepatitis in Asia. The most common indication for LT due to ESLD in west is alcoholic cirrhosis and hepatitis C virus (HCV), while hepatitis B virus (HBV) predominates in the east. There is a variation in prognostic models for assessing candidature and prioritizing organ allocation across the world. Model for end–stage liver disease (MELD) is followed in United States and some European centers. Other European countries rely on the Child–Turcotte–Pugh (CTP) score. Some parts of Asia still follow chronological order of listing. The debate regarding the best model for organ allocation is far from over. PMID:25755506

  19. Nutritional Status and Liver Transplantation

    PubMed Central

    Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

    2012-01-01

    Chronic liver disease has a profound effect on nutritional status and undernourishment is almost universally present in patients with end-stage liver disease undergoing liver transplantation. In the last decades, due to epidemiological changes, a trend showing an increase in patients with end-stage liver disease and associated obesity has also been reported in developed countries. Nutrition abnormalities may influence the outcome after transplantation therefore, the importance to carefully assess the nutritional status in the work-up of patients candidates for liver transplantation is widely accepted. More attention has been given to malnourished patients as they represent the greater number. The subjective global nutritional assessment and anthropometric measurements are recognized in current guidelines to be adequate in identifying those patients at risk of malnutrition. Cirrhotic patients with a depletion in lean body mass and fat deposits have an increased surgical risk and malnutrition may impact on morbidity, mortality and costs in the post-transplantation setting. For this reason an adequate calorie and protein intake should always be ensured to malnourished cirrhotic patient either through the diet, or using oral nutritional supplements or by enteral or parenteral nutrition although studies supporting the efficacy of nutritional supplementation in improving the clinical outcomes after transplantation are still scarce. When liver function is restored, an amelioration in the nutritional status is expected. After liver transplantation in fact dietary intake rapidly normalizes and fat mass is progressively regained while the recovery of muscle mass can be slower. In some patients unregulated weight gain may lead to over-nutrition and may favor metabolic disorders (hypertension, hyperglycemia, hyperlipidemia). This condition, defined as metabolic syndrome, may play a negative role on the overall survival of liver transplant patients. In this report we review data on nutrition and liver transplantation. PMID:25755385

  20. Extracorporeal liver support devices for listed patients.

    PubMed

    Lee, Karla C L; Stadlbauer, Vanessa; Jalan, Rajiv

    2016-06-01

    An alternative to liver transplantation for patients with liver failure remains an unmet need. In acute liver failure, the ideal extracorporeal liver support device (ELSD) would replace the functions of the failing liver in order to permit spontaneous recovery, given the incredible regenerative potential of the liver, negating the need for transplantation. In acute-on-chronic liver failure, an ELSD would ideally support hepatic function until a recovery to liver function before acute decompensation or until liver transplantation. In decompensated cirrhosis, an ELSD could again be used to support hepatic function until transplant. In addition, ELSDs may have the potential to treat the multiorgan failure that accompanies liver failure including hepatic encephalopathy, renal failure, and immune dysfunction or indeed potential to promote liver regeneration. Creation of an extracorporeal bioartificial liver able to completely replace liver function remains an unmet need. This review will describe a number of technologies suitable for clinical trials in humans, which have resulted from decades of engineering and biological research to develop a bioreactor able to adequately sustain functional hepatocytes. In addition, this review will describe artificial liver support devices that are primarily designed to replace the detoxifying functions of the liver and will consider the current data available or studies required to support their use in liver failure patients on the transplant waiting list. Liver Transplantation 22 839-848 2016 AASLD. PMID:26785141

  1. Interventional Radiology in Liver Transplantation

    SciTech Connect

    Karani, John B. Yu, Dominic F.Q.C.; Kane, Pauline A.

    2005-04-15

    Radiology is a key specialty within a liver transplant program. Interventional techniques not only contribute to graft and recipient survival but also allow appropriate patient selection and ensure that recipients with severe liver decompensation, hepatocellular carcinoma or portal hypertension are transplanted with the best chance of prolonged survival. Equally inappropriate selection for these techniques may adversely affect survival. Liver transplantation is a dynamic field of innovative surgical techniques with a requirement for interventional radiology to parallel these developments. This paper reviews the current practice within a major European center for adult and pediatric transplantation.

  2. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    ClinicalTrials.gov

    2014-03-20

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  3. Liver diseases in pregnancy: liver transplantation in pregnancy.

    PubMed

    Hammoud, Ghassan M; Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat; Ibdah, Jamal A

    2013-11-21

    Pregnancy in patients with advanced liver disease is uncommon as most women with decompensated cirrhosis are infertile and have high rate of anovulation. However, if gestation ensued; it is very challenging and carries high risks for both the mother and the baby such as higher rates of spontaneous abortion, prematurity, pulmonary hypertension, splenic artery aneurysm rupture, postpartum hemorrhage, and a potential for life-threatening variceal hemorrhage and hepatic decompensation. In contrary, with orthotopic liver transplantation, menstruation resumes and most women of childbearing age are able to conceive, give birth and lead a better quality of life. Women with orthotopic liver transplantation seeking pregnancy should be managed carefully by a team consultation with transplant hepatologist, maternal-fetal medicine specialist and other specialists. Pregnant liver transplant recipients need to stay on immunosuppression medication to prevent allograft rejection. Furthermore, these medications need to be monitored carefully and continued throughout pregnancy to avoid potential adverse effects to mother and baby. Thus delaying pregnancy 1 to 2 years after transplantation minimizes fetal exposure to high doses of immunosuppressants. Pregnant female liver transplant patients have a high rate of cesarean delivery likely due to the high rate of prematurity in this population. Recent reports suggest that with close monitoring and multidisciplinary team approach, most female liver transplant recipient of childbearing age will lead a successful pregnancy. PMID:24282354

  4. Radiology of liver circulation

    SciTech Connect

    Hermine, C.L.

    1985-01-01

    This book proposes that careful evaluation of the arterioportogram is the cornerstone in assessing portal flow obstruction, being the most consistent of all observations including liver histology, portal venous pressure, size and number of portosystemic collaterals, and wedged hepatic venous pressure. Very brief chapters cover normal hepatic circulation and angiographic methods. Contrast volumes and flow rates for celiac, hepatic, and superior mesenteric injection are given, with the timing for venous phase radiographs. In the main body of the text, portal obstruction is divided very simply into presinusoidal (all proximal causes) and postsinusoidal (all distal causes, including Budd-Chiari). Changes are discussed regarding the splenic artery and spleen; hepatic artery and its branches; portal flow rate and direction; and arterioportal shunting and portosystemic collateral circulation in minimal, moderate, severe, and very severe portal obstruction and in recognizable entities such as prehepatic portal and hepatic venous obstructions. The major emphasis in this section is the recognition and understanding of flow changes by which level and severity of obstruction are assessed (not simply the anatomy of portosystemic collateral venous flow). Excellent final chapters discuss the question of portal hypertension without obstruction, and the contribution of arterioportography to the treatment of portal hypertension, again with an emphasis on hemodynamics before and after shunt surgery. There is a fascinating final chapter on segmental intrahepatic obstruction without portal hypertension that explains much of the unusual contrast enhancement sometimes seen in CT scanning of hepatic mass lesions.

  5. Cholestatic Liver Disease in Children

    PubMed Central

    Santos, Jorge L.; Choquette, Monique

    2010-01-01

    Inherited syndromes of intrahepatic cholestasis and biliary atresia are the most common causes of chronic liver disease and the prime indication for liver transplantation in children. Our understanding of the pathogenesis of these diseases has increased substantially by the discovery of genetic mutations in children with intrahepatic cholestasis and the findings that inflammatory circuits are operative at the time of diagnosis of biliary atresia. Building on this solid foundation, recent studies provide new insight into genotype-phenotype relationships and how mutations produce altered bile composition and cholestasis. New evidence exists that although liver transplantation is curative for patients with end-stage liver disease owing to cholestasis, some patients may develop recurrence of cholestasis because of the emergence of autoantibodies that disrupt canalicular function in the new graft. Progress is also evident in biliary atresia, with recent studies identifying candidate modifier genes and directly implicating lymphocytes and inflammatory signals in the pathogenesis of bile duct injury and obstruction. PMID:20425482

  6. Drugs Approved for Liver Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  7. Infections After Orthotopic Liver Transplantation

    PubMed Central

    Pedersen, Mark; Seetharam, Anil

    2014-01-01

    Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. PMID:25755581

  8. Biomarkers in Pediatric Liver Disease.

    PubMed

    Kyrana, Eirini; Fitzpatrick, Emer; Dhawan, Anil

    2016-01-01

    The chronic nature of liver diseases in children and adults merits close follow-up for disease progression and/or treatment evaluation. Disease progression involves injury to liver cells resulting in cell death, varying degrees of inflammation, steatosis depending on the insult, oxidative stress, and eventually fibrosis and cirrhosis unless the process is modified with treatment or spontaneous recovery. Inflammation, cell death, and fibrosis are the three major processes that determine the outcome of liver disease irrespective of the etiology. Markers to measure the activity or status of these parameters in a dynamic way, particularly via noninvasive methods, are urgently required. In this chapter, we summarize recent advances in the identification of biomarkers of liver diseases: biomarkers corresponding to inflammation, cell death, fibrosis, and the development of malignancy. PMID:26764473

  9. Liver Disease and Adult Vaccination

    MedlinePlus

    ... visit Healthmap Vaccine Finder . Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  10. Liver abscesses in feedlot cattle.

    PubMed

    Nagaraja, T G; Lechtenberg, Kelly F

    2007-07-01

    Liver abscesses in feedlot cattle result from aggressive grain-feeding programs and are influenced by a number of dietary and management factors. They have a major economic impact on the feedlot industry because of liver condemnation and reduced animal performance and carcass yield. Ruminal lesions resulting from acidosis usually are accepted as the predisposing factors. Generally, control of liver abscesses in feedlot cattle has depended on the use of tylosin, which reduces abscess incidence by 40% to 70%. However, new methods and products for liver abscess control are needed. Corn milling by-products that are less fermentable may aide in the quest for cattle production techniques that lead to lower usage of antimicrobials. A vaccine is also commercially available. PMID:17606156

  11. What's New in Liver Cancer Research?

    MedlinePlus

    ... for liver cancer is no longer working? What`s New in Liver Cancer Research? What`s new in liver cancer research and treatment? Other Resources ... Cancer Talking With Your Doctor After Treatment What`s New in Liver Cancer Research? Other Resources and References ...

  12. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  13. Drinking water and liver cancer

    PubMed Central

    Ruan, Cui-Cai; Chen, Yan-Hua; Zhang, Zhen-Quan

    1997-01-01

    AIM: To study the relationship between the mutagenicity of drinking water and incidence of liver cancer in high liver cancer incidence areas in Guangxi. METHODS: A relationship between the mutagenicity of drinking water and incidence of liver cancer was studied in Fusui County, a high liver cancer incidence area in China. Thirty-two samples of different kinds of drinking water (13 samples of pond water, 3 samples of well water near the ponds, 5 samples of well water, 6 samples of river water and 5 samples of tap water) were tested with a micronuclear technique in the root tips of Vicia faba. RESULTS: Among the 32 samples of different kinds of drinking water, 12 samples of pond water and 2 samples of well water near the ponds induced micronucleus frequencies on the root tips of Vicia faba to increase (P < 0.01), with the average micronucleus rate being 15.8% and 11.7%, respectively, while there was no difference between the micronucleus frequencies on the root tips of Vicia faba induced by well water (4.3%), river water (3.9%) or tap water (4.2%) and that on the control group (P > 0.05). Micronuclear effects on the root tips of Vicia faba in different kinds of drinking water were positively related to the incidence of liver cancer (r = 0.86, P < 0.05). CONCLUSION: There were substances that caused chromosomal aberrations in the drinking pond water in high liver cancer incidence areas of Guangxi. Different kinds of drinking water were closely related to the incidence of liver cancer. Chemical mutagens in the water may be an important factor in the high incidence of human liver cancer. PMID:27006586

  14. Energy Metabolism in the Liver

    PubMed Central

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

  15. Osteoporosis across chronic liver disease.

    PubMed

    Guarino, M; Loperto, I; Camera, S; Cossiga, V; Di Somma, C; Colao, A; Caporaso, N; Morisco, F

    2016-06-01

    Osteoporosis is a complication of chronic liver disease, with impact on morbidity, quality of life, and survival. The progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with liver disease. So, it is fundamental to make better the quality of life and to prevent complications. Metabolic bone disorders are common complications of chronic liver disease (CLD). Patients with CLD have an increased risk of bone fractures, with significant impact on morbidity, quality of life, and even on survival. Bone diseases, including osteomalacia, osteoporosis, and osteopenia, are frequently observed in many types of liver disease. The pathogenesis of damage and the mechanisms of bone loss are different in relation to the specific liver disease. The relevance of these conditions induced many authors to create a new nosographic entity known as "hepatic osteodystrophy", although this term is rarely used anymore and it is now commonly referred to as osteopenia or osteoporosis associated with chronic liver disease. This review is based on the personal experiences of the authors and upon research done of the available literature on this subject matter. The authors searched the PubMed database for publications containing the term "liver disease" in combination with "bone disease", "hepatic osteodistrophy", "osteoporosis", "osteopenia", "osteomalacia", and "fractures". They selected publications from the past 10 years but did not exclude older seminal publications, especially for colestatic liver diseases. This review of literature shows that osteoporosis crosses all CLD. It is important to underline that the progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with CLD. It is fundamental to make better the quality of life and it is mandatory to prevent complications and in particular the osteoporotic ones, especially fractures. PMID:26846777

  16. Transarterial Therapy for Colorectal Liver Metastases.

    PubMed

    Bhutiani, Neal; Martin, Robert C G

    2016-04-01

    Until recently, hepatic arterial therapies (HAT) had been used for colorectal liver metastases after failure of first-, second-, and third-line chemotherapies. HAT has gained greater acceptance in patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The current data demonstrate that HAT is a safe and effective option for preoperative downsizing, optimizing the time to surgery, limiting non-tumor-bearing liver toxicity, and improving overall survival after surgery in patients with colorectal liver-only metastases. The aim of this review is to present the current data for HAT in liver-only and liver-dominant colorectal liver metastases. PMID:27017870

  17. EGFR Signaling in Liver Diseases.

    PubMed

    Komposch, Karin; Sibilia, Maria

    2016-01-01

    The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that is activated by several ligands leading to the activation of diverse signaling pathways controlling mainly proliferation, differentiation, and survival. The EGFR signaling axis has been shown to play a key role during liver regeneration following acute and chronic liver damage, as well as in cirrhosis and hepatocellular carcinoma (HCC) highlighting the importance of the EGFR in the development of liver diseases. Despite the frequent overexpression of EGFR in human HCC, clinical studies with EGFR inhibitors have so far shown only modest results. Interestingly, a recent study has shown that in human HCC and in mouse HCC models the EGFR is upregulated in liver macrophages where it plays a tumor-promoting function. Thus, the role of EGFR in liver diseases appears to be more complex than what anticipated. Further studies are needed to improve the molecular understanding of the cell-specific signaling pathways that control disease development and progression to be able to develop better therapies targeting major components of the EGFR signaling network in selected cell types. In this review, we compiled the current knowledge of EGFR signaling in different models of liver damage and diseases, mainly derived from the analysis of HCC cell lines and genetically engineered mouse models (GEMMs). PMID:26729094

  18. Energy metabolism in the liver.

    PubMed

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. PMID:24692138

  19. Biliary Strictures after Liver Transplantation

    PubMed Central

    Ryu, Choong Heon

    2011-01-01

    Biliary strictures are one of the most common complications following liver transplantation, representing an important cause of morbidity and mortality in transplant recipients. The reported incidence of biliary stricture is 5% to 15% following deceased donor liver transplantations and 28% to 32% following living donor liver transplantations. Bile duct strictures following liver transplantation are easily and conveniently classified as anastomotic strictures (AS) or non-anastomotic strictures (NAS). NAS are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and the need for retransplantation. Current endoscopic strategies to correct biliary strictures following liver transplantation include repeated balloon dilatations and the placement of multiple side-by-side plastic stents. Endoscopic balloon dilatation with stent placement is successful in the majority of AS patients. In patients for whom gaining biliary access is technically difficult, a combined endoscopic and percutaneous/surgical approach proves quite useful. Future directions, including novel endoscopic retrograde cholangiopancreatography techniques, advanced endoscopy, and improved stents could allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. The aim of this review is to detail the present status of endoscopy in the diagnosis, treatment, outcome, and future directions of biliary strictures related to orthotopic liver transplantation from the viewpoint of a clinical gastroenterologists. PMID:21814591

  20. Neurologic complications after liver transplantation

    PubMed Central

    Živković, Saša A

    2013-01-01

    Neurologic complications are relatively common after solid organ transplantation and affect 15%-30% of liver transplant recipients. Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections. Most common complications include seizures and encephalopathy, and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients. Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor, headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement. Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system (CNS) infections, but viral and fungal CNS infections still affect 1% of liver transplant recipients, and the morbidity and mortality in the affected patients remain fairly high. Critical illness myopathy may also affect up to 7% of liver transplant recipients. Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation. Accurate diagnosis and timely intervention are essential to improve outcomes, while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting. PMID:24023979

  1. Lipids in liver transplant recipients

    PubMed Central

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-01-01

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  2. EGFR Signaling in Liver Diseases

    PubMed Central

    Komposch, Karin; Sibilia, Maria

    2015-01-01

    The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that is activated by several ligands leading to the activation of diverse signaling pathways controlling mainly proliferation, differentiation, and survival. The EGFR signaling axis has been shown to play a key role during liver regeneration following acute and chronic liver damage, as well as in cirrhosis and hepatocellular carcinoma (HCC) highlighting the importance of the EGFR in the development of liver diseases. Despite the frequent overexpression of EGFR in human HCC, clinical studies with EGFR inhibitors have so far shown only modest results. Interestingly, a recent study has shown that in human HCC and in mouse HCC models the EGFR is upregulated in liver macrophages where it plays a tumor-promoting function. Thus, the role of EGFR in liver diseases appears to be more complex than what anticipated. Further studies are needed to improve the molecular understanding of the cell-specific signaling pathways that control disease development and progression to be able to develop better therapies targeting major components of the EGFR signaling network in selected cell types. In this review, we compiled the current knowledge of EGFR signaling in different models of liver damage and diseases, mainly derived from the analysis of HCC cell lines and genetically engineered mouse models (GEMMs). PMID:26729094

  3. Lipids in liver transplant recipients.

    PubMed

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-03-28

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  4. Comparative Study of Human Liver Ferritin and Chicken Liver by Mössbauer Spectroscopy. Preliminary Results

    NASA Astrophysics Data System (ADS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

    2004-12-01

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Mössbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Mössbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  5. Intrahepatic Cholangiocarcinoma Masquerading as Liver Abscess

    PubMed Central

    Shah, Vinit; Arora, Anil; Tyagi, Pankaj; Sharma, Praveen; Bansal, Naresh; Singla, Vikas; Bansal, Rinkesh K.; Gupta, Varun; Kumar, Ashish

    2015-01-01

    Malignancy masquerading as liver abscess, and presenting with fever, is mainly described in patients with colorectal cancers with liver metastasis. Primary liver tumors such as hepatocellular carcinoma or intrahepatic cholangiocarcinoma presenting as non-resolving liver abscess is extremely uncommon and carries a dismal prognosis. We present a rare case of non-resolving liver abscess as a presenting manifestation of intrahepatic cholangiocarcinoma. PMID:25941437

  6. Segmentation of liver and liver tumor for the Liver-Workbench

    NASA Astrophysics Data System (ADS)

    Zhou, Jiayin; Ding, Feng; Xiong, Wei; Huang, Weimin; Tian, Qi; Wang, Zhimin; Venkatesh, Sudhakar K.; Leow, Wee Kheng

    2011-03-01

    Robust and efficient segmentation tools are important for the quantification of 3D liver and liver tumor volumes which can greatly help clinicians in clinical decision-making and treatment planning. A two-module image analysis procedure which integrates two novel semi-automatic algorithms has been developed to segment 3D liver and liver tumors from multi-detector computed tomography (MDCT) images. The first module is to segment the liver volume using a flippingfree mesh deformation model. In each iteration, before mesh deformation, the algorithm detects and avoids possible flippings which will cause the self-intersection of the mesh and then the undesired segmentation results. After flipping avoidance, Laplacian mesh deformation is performed with various constraints in geometry and shape smoothness. In the second module, the segmented liver volume is used as the ROI and liver tumors are segmented by using support vector machines (SVMs)-based voxel classification and propagational learning. First a SVM classifier was trained to extract tumor region from one single 2D slice in the intermediate part of a tumor by voxel classification. Then the extracted tumor contour, after some morphological operations, was projected to its neighboring slices for automated sampling, learning and further voxel classification in neighboring slices. This propagation procedure continued till all tumorcontaining slices were processed. The performance of the whole procedure was tested using 20 MDCT data sets and the results were promising: Nineteen liver volumes were successfully segmented out, with the mean relative absolute volume difference (RAVD), volume overlap error (VOE) and average symmetric surface distance (ASSD) to reference segmentation of 7.1%, 12.3% and 2.5 mm, respectively. For live tumors segmentation, the median RAVD, VOE and ASSD were 7.3%, 18.4%, 1.7 mm, respectively.

  7. Toward surface quantification of liver fibrosis progression

    NASA Astrophysics Data System (ADS)

    He, Yuting; Kang, Chiang Huen; Xu, Shuoyu; Tuo, Xiaoye; Trasti, Scott; Tai, Dean C. S.; Raja, Anju Mythreyi; Peng, Qiwen; So, Peter T. C.; Rajapakse, Jagath C.; Welsch, Roy; Yu, Hanry

    2010-09-01

    Monitoring liver fibrosis progression by liver biopsy is important for certain treatment decisions, but repeated biopsy is invasive. We envision redefinition or elimination of liver biopsy with surface scanning of the liver with minimally invasive optical methods. This would be possible only if the information contained on or near liver surfaces accurately reflects the liver fibrosis progression in the liver interior. In our study, we acquired the second-harmonic generation and two-photon excitation fluorescence microscopy images of liver tissues from bile duct-ligated rat model of liver fibrosis. We extracted morphology-based features, such as total collagen, collagen in bile duct areas, bile duct proliferation, and areas occupied by remnant hepatocytes, and defined the capsule and subcapsular regions on the liver surface based on image analysis of features. We discovered a strong correlation between the liver fibrosis progression on the anterior surface and interior in both liver lobes, where biopsy is typically obtained. The posterior surface exhibits less correlation with the rest of the liver. Therefore, scanning the anterior liver surface would obtain similar information to that obtained from biopsy for monitoring liver fibrosis progression.

  8. Liver-Regenerative Transplantation: Regrow and Reset.

    PubMed

    Collin de l'Hortet, A; Takeishi, K; Guzman-Lepe, J; Handa, K; Matsubara, K; Fukumitsu, K; Dorko, K; Presnell, S C; Yagi, H; Soto-Gutierrez, A

    2016-06-01

    Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)-derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation. PMID:26699680

  9. Maximum residue level validation of triclabendazole marker residues in bovine liver, muscle and milk matrices by ultra high pressure liquid chromatography tandem mass spectrometry.

    PubMed

    Whelan, Michelle; O'Mahony, John; Moloney, Mary; Cooper, Kevin M; Furey, Ambrose; Kennedy, D Glenn; Danaher, Martin

    2013-02-01

    Triclabendazole is the only anthelmintic drug, which is active against immature, mature and adult stages of fluke. The objective of this work was to develop an analytical method to quantify and confirm the presence of triclabendazole residues around the MRL. In this work, a new analytical method was developed, which extended dynamic range to 1-100 and 5-1000 μg kg(-1) for milk and tissue, respectively. This was achieved using a mobile phase containing trifluoroacetic acid (pK(a) of 0.3), which resulted in the formation of the protonated pseudomolecular ions, [M+H](+), of triclabendazole metabolites. Insufficient ionisation of common mobile phase additives due to low pK(a) values (<2) was identified as the cause of poor linearity. The new mobile phase conditions allowed the analysis of triclabendazole residues in liver, muscle and milk encompassing their EU maximum residue levels (MRL) (250, 225 and 10 μg kg(-1) respectively). Triclabendazole residues were extracted using a modified QuEChERS method and analysed by positive electrospray ionisation mass spectrometry with all analytes eluted by 2.23 min. The method was validated at the MRL according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCα) of the method was in the range of 250.8-287.2, 2554.9-290.8 and 10.9-12.1 μg kg(-1) for liver, muscle and milk, respectively. The performance of the method was successfully verified for triclabendazole in muscle by participating in a proficiency study, the method was also applied to incurred liver, muscle and milk samples. PMID:23290363

  10. Gut-liver axis in alcoholic liver disease.

    PubMed

    Szabo, Gyongyi

    2015-01-01

    Alcoholic liver disease (ALD) has been among the leading causes of cirrhosis and liver-related death worldwide for decades. Early discoveries in alcoholic liver disease identified increased levels of bacterial endotoxin in the portal circulation, suggesting a role for gut-derived toxins in ALD. Indeed, alcohol consumption can disrupt the intestinal epithelial barrier and result in increased gut permeability that increasingly is recognized as a major factor in ALD. Bacterial endotoxin, lipopolysaccharide, is a prototypic microbe-derived inflammatory signal that contributes to inflammation in ALD through activation of the Toll-like receptor 4. Recent studies also have shown that alcohol consumption is associated with alterations in the gut microbiome, and the dysbalance of pathogenic and commensal organisms in the intestinal microbiome may contribute to the abnormal gut-liver axis in ALD. Indeed, bacterial decontamination improves ALD both in human and animal models. This short review summarizes recent findings and highlights emerging trends in the gut-liver axis relevant to ALD. PMID:25447847

  11. Cell sources, liver support systems and liver tissue engineering: alternatives to liver transplantation.

    PubMed

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-05-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  12. Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation

    PubMed Central

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-01-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  13. Drug-induced liver injury.

    PubMed

    Leise, Michael D; Poterucha, John J; Talwalkar, Jayant A

    2014-01-01

    Drug hepatoxicity can be nonidiosyncratic (predictable), as in the case of acetaminophen, or idiosyncratic (unpredictable). This review article focuses primarily on idiosyncratic drug-induced liver injury (DILI). New epidemiologic data suggest that approximately 20 new cases of DILI per 100,000 persons occur each year. Idiosyncratic DILI accounts for 11% of the cases of acute liver failure in the United States. Risk factors for DILI include medication dose, drug lipophilicity, and extent of hepatic metabolism. There is mixed evidence to support the role of host factors such as age, sex, and chronic liver disease in the development of DILI. For specific drugs, a genetic predisposition appears to be a risk factor for DILI. Suspected cases of idiosyncratic DILI should be categorized as hepatitic, cholestatic, or mixed on the basis of the degree/ratio of abnormalities in the alanine aminotransferase and alkaline phosphatase. A careful evaluation for other causes of liver disease should be performed, though a liver biopsy is rarely needed. There is evidence that some patients with DILI may actually have hepatitis E and this diagnosis should be considered. Amoxicillin/clavulanate isoniazid, and nonsteroidal anti-inflammatory drugs are among the most common causes of DILI. Drug discontinuation or dechallenge should lead to an improvement in liver biochemistries in most patients, though a bilirubin value of more than 3 g/dL is associated with mortality of at least 10%. New biomarkers for DILI using proteomics and micro RNA appear promising but require further study. New studies on drugs with potential for causing DILI are reviewed herein, including tumor necrosis factor-alpha antagonists, fluoroquinolones, tyrosine kinase inhibitors, statins, and supplements. PubMed was used with search terms of drug induced liver injury OR DILI with filter settings of "English language" and "humans" and custom date range of "January 1, 2000." The authors also manually searched bibliographies from key references and included seminal references before the year 2000. PMID:24388027

  14. Autophagy regulates sphingolipid levels in the liver[S

    PubMed Central

    Alexaki, Aikaterini; Gupta, Sita D.; Majumder, Saurav; Kono, Mari; Tuymetova, Galina; Harmon, Jeffrey M.; Dunn, Teresa M.; Proia, Richard L.

    2014-01-01

    Sphingolipid levels are tightly regulated to maintain cellular homeostasis. During pathologic conditions such as in aging, inflammation, and metabolic and neurodegenerative diseases, levels of some sphingolipids, including the bioactive metabolite ceramide, are elevated. Sphingolipid metabolism has been linked to autophagy, a critical catabolic process in both normal cell function and disease; however, the in vivo relevance of the interaction is not well-understood. Here, we show that blocking autophagy in the liver by deletion of the Atg7 gene, which is essential for autophagosome formation, causes an increase in sphingolipid metabolites including ceramide. We also show that overexpression of serine palmitoyltransferase to elevate de novo sphingolipid biosynthesis induces autophagy in the liver. The results reveal autophagy as a process that limits excessive ceramide levels and that is induced by excessive elevation of de novo sphingolipid synthesis in the liver. Dysfunctional autophagy may be an underlying mechanism causing elevations in ceramide that may contribute to pathogenesis in diseases. PMID:25332431

  15. Hepatic inflammation and progressive liver fibrosis in chronic liver disease

    PubMed Central

    Czaja, Albert J

    2014-01-01

    Chronic liver inflammation drives hepatic fibrosis, and current immunosuppressive, anti-inflammatory, and anti-viral therapies can weaken this driver. Hepatic fibrosis is reversed, stabilized, or prevented in 57%-79% of patients by conventional treatment regimens, mainly by their anti-inflammatory actions. Responses, however, are commonly incomplete and inconsistently achieved. The fibrotic mechanisms associated with liver inflammation have been clarified, and anti-fibrotic agents promise to improve outcomes as adjunctive therapies. Hepatitis C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within hepatocytes. Angiotensin can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen species. Anti-oxidants (N-acetylcysteine, S-adenosyl-L-methionine, and vitamin E) and angiotensin inhibitors (losartin) have had anti-fibrotic actions in preliminary human studies, and they may emerge as supplemental therapies. Anti-fibrotic agents presage a new era of supplemental treatment for chronic liver disease. PMID:24627588

  16. Adult living donor liver imaging

    PubMed Central

    Cai, Larry; Yeh, Benjamin M.; Westphalen, Antonio C.; Roberts, John P.; Wang, Zhen J.

    2016-01-01

    Adult living donor liver transplantation (LDLT) is increasingly used for the treatment of end-stage liver disease. The three most commonly harvested grafts for LDLT are left lateral segment, left lobe, and right lobe grafts. The left lateral segment graft, which includes Couinaud’s segments II and III, is usually used for pediatric recipients or small size recipients. Most of the adult recipients need either a left or a right lobe graft. Whether a left or right lobe graft should be harvested from the donors depends on estimated graft and donor remnant liver volume, as well as biliary and vascular anatomy. Detailed preoperative assessment of the potential donor liver volumetrics, biliary and vascular anatomy, and liver parenchyma is vital to minimize risks to the donors and maximize benefits to the recipients. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently the imaging modalities of choice in the preoperative evaluation of potential donors. This review provides an overview of key surgical considerations in LDLT that the radiologists must be aware of, and imaging findings on CT and MRI that the radiologists must convey to the surgeons when evaluating potential donors for LDLT. PMID:26912106

  17. Adult living donor liver imaging.

    PubMed

    Cai, Larry; Yeh, Benjamin M; Westphalen, Antonio C; Roberts, John P; Wang, Zhen J

    2016-01-01

    Adult living donor liver transplantation (LDLT) is increasingly used for the treatment of end-stage liver disease. The three most commonly harvested grafts for LDLT are left lateral segment, left lobe, and right lobe grafts. The left lateral segment graft, which includes Couinaud's segments II and III, is usually used for pediatric recipients or small size recipients. Most of the adult recipients need either a left or a right lobe graft. Whether a left or right lobe graft should be harvested from the donors depends on estimated graft and donor remnant liver volume, as well as biliary and vascular anatomy. Detailed preoperative assessment of the potential donor liver volumetrics, biliary and vascular anatomy, and liver parenchyma is vital to minimize risks to the donors and maximize benefits to the recipients. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently the imaging modalities of choice in the preoperative evaluation of potential donors. This review provides an overview of key surgical considerations in LDLT that the radiologists must be aware of, and imaging findings on CT and MRI that the radiologists must convey to the surgeons when evaluating potential donors for LDLT. PMID:26912106

  18. Focal liver lesions found incidentally

    PubMed Central

    Algarni, Abdullah A; Alshuhri, Abdullah H; Alonazi, Majed M; Mourad, Moustafa Mabrouk; Bramhall, Simon R

    2016-01-01

    Incidentally found focal liver lesions are a common finding and a reason for referral to hepatobiliary service. They are often discovered in patients with history of liver cirrhosis, colorectal cancer, incidentally during work up for abdominal pain or in a trauma setting. Specific points should considered during history taking such as risk factors of liver cirrhosis; hepatitis, alcohol consumption, substance exposure or use of oral contraceptive pills and metabolic syndromes. Full blood count, liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease. Imaging should start with B-mode ultrasound. If available, contrast enhanced ultrasound is a feasible, safe, cost effective option and increases the ability to reach a diagnosis. Contrast enhanced computed tomography should be considered next. It is more accurate in diagnosis and better to study anatomy for possible operation. Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity. If doubt still remains, the options are biopsy or surgical excision. PMID:27028805

  19. Diverse routes to liver regeneration.

    PubMed

    Alison, Malcolm R; Lin, Wey-Ran

    2016-02-01

    The liver's ability to regenerate is indisputable; for example, after a two-thirds partial hepatectomy in rats all residual hepatocytes can divide, questioning the need for a specific stem cell population. On the other hand, there is a potential stem cell compartment in the canals of Hering, giving rise to ductular reactions composed of hepatic progenitor cells (HPCs) when the liver's ability to regenerate is hindered by replicative senescence, but the functional relevance of this response has been questioned. Several papers have now clarified regenerative mechanisms operative in the mouse liver, suggesting that the liver is possibly unrivalled in its versatility to replace lost tissue. Under homeostatic conditions a perivenous population of clonogenic hepatocytes operates, whereas during chronic damage a minor population of periportal clonogenic hepatocytes come to the fore, while the ability of HPCs to completely replace the liver parenchyma has now been shown. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26510495

  20. Responsibility, alcoholism, and liver transplantation.

    PubMed

    Glannon, W

    1998-02-01

    Many believe that it is morally wrong to give lower priority for a liver transplant to alcoholics with end-stage liver disease than to patients whose disease is not alcohol-related. Presumably, alcoholism is a disease that results from factors beyond one's control and therefore one cannot be causally or morally responsible for alcoholism or the liver failure that results from it. Moreover, giving lower priority to alcoholics unfairly singles them out for the moral vice of heavy drinking. I argue that the etiology of alcoholism may involve enough control for the alcoholic to be responsible for his condition and accordingly have a weaker claim to receive a new liver than someone who acquires the disease through no fault of his own. In addition, I show why it is more plausible to reframe the question of priority in terms of control and responsibility rather than virtue and vice. Given that medical resources like livers are scarce, some people may justifiably be given lower priority than others in receiving these resources. PMID:9555633

  1. Hydroxycut-induced Liver Toxicity

    PubMed Central

    Kaswala, DH; Shah, S; Patel, N; Raisoni, S; Swaminathan, S

    2014-01-01

    In the recent era, use of various nutritional supplements is highly encouraged amongst the people of United States. Weight loss supplements are major part of the nutritional supplements and their usage is unregulated in the US. Obesity is a major health concern in the US and Americans spend around $30 billion a year for weight loss supplements. At times, these supplements can be responsible for documented or undocumented adverse drug effects. The health consequences related to these supplements are often overlooked by the general public, even though FDA issues advisories regarding them. One common supplement used for weight loss was Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada). Hydroxycut was recalled from the market after a FDA warning in May 2009 because of 23 reports of serious health problems ranging from jaundice and elevated liver enzymes to liver damage. 1 This case report adds evidence for Hydroxycut - induced hepatotoxicity. A 27 year old man with right upper quadrant pain and jaundice was found to have elevated liver enzymes and was taking Hydroxycut along with other supplements. Liver biopsy showed drug induced hepatotoxicity. Discontinuation of Hydroxycut dramatically improved liver functions and related symptoms. PMID:24669349

  2. Cholangiocyte proliferation and liver fibrosis

    PubMed Central

    Glaser, Shannon S.; Gaudio, Eugenio; Miller, Tim; Alvaro, Domenico; Alpini, Gianfranco

    2009-01-01

    Cholangiocyte proliferation is triggered during extrahepatic bile duct obstruction induced by bile duct ligation, which is a common in vivo model used for the study of cholangiocyte proliferation and liver fibrosis. The proliferative response of cholangiocytes during cholestasis is regulated by the complex interaction of several factors, including gastrointestinal hormones, neuroendocrine hormones and autocrine or paracrine signalling mechanisms. Activation of biliary proliferation (ductular reaction) is thought to have a key role in the initiation and progression of liver fibrosis. The first part of this review provides an overview of the primary functions of cholangiocytes in terms of secretin-stimulated bicarbonate secretion – a functional index of cholangiocyte growth. In the second section, we explore the important regulators, both inhibitory and stimulatory, that regulate the cholangiocyte proliferative response during cholestasis. We discuss the role of proliferating cholangiocytes in the induction of fibrosis either directly via epithelial mesenchymal transition or indirectly via the activation of other liver cell types. The possibility of targeting cholangiocyte proliferation as potential therapy for reducing and/or preventing liver fibrosis, and future avenues for research into how cholangiocytes participate in the process of liver fibrogenesis are described. PMID:19239726

  3. Focal liver lesions found incidentally.

    PubMed

    Algarni, Abdullah A; Alshuhri, Abdullah H; Alonazi, Majed M; Mourad, Moustafa Mabrouk; Bramhall, Simon R

    2016-03-28

    Incidentally found focal liver lesions are a common finding and a reason for referral to hepatobiliary service. They are often discovered in patients with history of liver cirrhosis, colorectal cancer, incidentally during work up for abdominal pain or in a trauma setting. Specific points should considered during history taking such as risk factors of liver cirrhosis; hepatitis, alcohol consumption, substance exposure or use of oral contraceptive pills and metabolic syndromes. Full blood count, liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease. Imaging should start with B-mode ultrasound. If available, contrast enhanced ultrasound is a feasible, safe, cost effective option and increases the ability to reach a diagnosis. Contrast enhanced computed tomography should be considered next. It is more accurate in diagnosis and better to study anatomy for possible operation. Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity. If doubt still remains, the options are biopsy or surgical excision. PMID:27028805

  4. Liver transplantation at Mount Sinai.

    PubMed

    Kim-Schluger, L; Florman, S S; Gondolesi, G; Emre, S; Sheiner, P A; Fishbein, T M; Schwartz, M E; Miller, C M

    2000-01-01

    Nearly 2000 liver transplants have been performed over the past 12 years at Mount Sinai, with a recent exponential growth in living donor surgeries. Living-donor liver transplantation has emerged as an important option for our patients with end-stage liver disease. We are only beginning to recognize fully the advantages that 'scheduled' liver transplantation can offer. In this era of severe cadaver organ shortages, living donation offers patients the option of liver replacement in a timely fashion, before life-threatening complications of hepatic failure and/or carcinoma progression prohibit transplantation. The next era of transplantation at Mount Sinai will bring significant increases in the number of transplants performed with living donors, with projections of over 50% of the total transplants each year expected to involve living donations. We are committed to offering this option while recognizing that donor safety remains paramount and cannot be overemphasized. Proper donor and recipient selection, as well as surgical experience are imperative to success with this technically demanding procedure. Recurrent disease after transplantation, particularly with hepatitis C, remains a challenge clinically. Further investigations into the pathogenesis of the rapid progression of recurrent hepatitis C need to be addressed. Living donor transplantation could be an important option for these patients and would allow timely transplantation and the potential for improved survival in patients with hepatocellular carcinoma. PMID:11512318

  5. Infections in liver transplant recipients

    PubMed Central

    Romero, Fabian A; Razonable, Raymund R

    2011-01-01

    Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications. In this article, we review the contemporary state of infectious complications during the post-operative period, with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation. Bacteria, and less commonly Candida infections, remain the predominant pathogens during the immediate post-operative period, especially during the first month, and infections caused by drug-resistant strains are emerging. Infections caused by cytomegalovirus and Aspergillus sp. present clinically during the “opportunistic” period characterized by intense immunosuppression. As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed, one potential adverse effect is an increase in certain infections. Hence, it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk, local antimicrobial resistance patterns, and surveillance. A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients. PMID:21603030

  6. Screening and identification of DNA aptamers toward Schistosoma japonicum eggs via SELEX

    PubMed Central

    Long, Yuqian; Qin, Zhiqiang; Duan, Minlan; Li, Shizhu; Wu, Xiaoqiu; Lin, Wei; Li, Jianglin; Zhao, Zilong; Liu, Jing; Xiong, Dehui; Huang, Yi; Hu, Xiaoxiao; Yang, Chao; Ye, Mao; Tan, Weihong

    2016-01-01

    Schistosomiasis is a major parasitic disease caused by blood flukes of the genus Schistosoma. Several million people all over the world are estimated to suffer from severe morbidity as a consequence of schistosomiasis. The worm’s eggs, which cause the symptoms of schistosomiasis, are generally used to diagnose the disease. In this study, we employed egg-based systematic evolution of ligands by exponential enrichment (egg-SELEX) and identified a panel of ssDNA aptamers specifically binding to eggs derived from S. japonicum. Among these, two aptamers LC6 and LC15 exhibited strong binding to and specific recognition of S. japonicum eggs, but not eggs from Fasciolopsis buski, Enterobius, Ascaris or Clonorchis sinensis. Furthermore, tissue imaging results revealed that LC15 could recognize S. japonicum eggs laid in liver tissues with a detection ratio of 80.5%. Collectively, therefore, we obtained useful aptamers specifically recognizing S. japonicum eggs, which will facilitate the development of an effective tool for both schistosomiasis diagnosis and drug delivery. PMID:27121794

  7. Metagonimus yokogawai: a 100-kDa Somatic Antigen Commonly Reacting with Other Trematodes

    PubMed Central

    Park, Young-Jin; Park, Jeong-Hyun; Chai, Jong-Yil

    2014-01-01

    This study was undertaken to characterize the properties of a 100 kDa somatic antigen from Metagonimus yokogawai. Monoclonal antibodies (mAbs) were produced against this 100 kDa antigen, and their immunoreactivity was assessed by western blot analysis with patients' sera. The mAbs against the 100 kDa antigen commonly reacted with various kinds of trematode antigens, including intestinal (Gymnophalloides seoi), lung (Paragonimus westermani), and liver flukes (Clonorchis sinensis and Fasciola hepatica). However, this mAb showed no cross-reactions with other helminth parasites, including nematodes and cestodes. To determine the topographic distribution of the 100 kDa antigen in worm sections, indirect immunoperoxidase staining was performed. A strong positive reaction was observed in the tegumental and subtegumental layers of adult M. yokogawai and C. sinensis. The results showed that the 100 kDa somatic protein of M. yokogawai is a common antigen which recognizes a target epitope present over the tegumental layer of different trematode species. PMID:24850966

  8. Screening and identification of DNA aptamers toward Schistosoma japonicum eggs via SELEX.

    PubMed

    Long, Yuqian; Qin, Zhiqiang; Duan, Minlan; Li, Shizhu; Wu, Xiaoqiu; Lin, Wei; Li, Jianglin; Zhao, Zilong; Liu, Jing; Xiong, Dehui; Huang, Yi; Hu, Xiaoxiao; Yang, Chao; Ye, Mao; Tan, Weihong

    2016-01-01

    Schistosomiasis is a major parasitic disease caused by blood flukes of the genus Schistosoma. Several million people all over the world are estimated to suffer from severe morbidity as a consequence of schistosomiasis. The worm's eggs, which cause the symptoms of schistosomiasis, are generally used to diagnose the disease. In this study, we employed egg-based systematic evolution of ligands by exponential enrichment (egg-SELEX) and identified a panel of ssDNA aptamers specifically binding to eggs derived from S. japonicum. Among these, two aptamers LC6 and LC15 exhibited strong binding to and specific recognition of S. japonicum eggs, but not eggs from Fasciolopsis buski, Enterobius, Ascaris or Clonorchis sinensis. Furthermore, tissue imaging results revealed that LC15 could recognize S. japonicum eggs laid in liver tissues with a detection ratio of 80.5%. Collectively, therefore, we obtained useful aptamers specifically recognizing S. japonicum eggs, which will facilitate the development of an effective tool for both schistosomiasis diagnosis and drug delivery. PMID:27121794

  9. Microbiota, immunity and the liver.

    PubMed

    Vaikunthanathan, T; Safinia, N; Lombardi, G; Lechler, R I

    2016-03-01

    The gut harbors a complex community of over 100 trillion microbial cells known to exist in symbiotic harmony with the host influencing human physiology, metabolism, nutrition and immune function. It is now widely accepted that perturbations of this close partnership results in the pathogenesis of several major diseases with increasing evidence highlighting their role outside of the intestinal tract. The intimate proximity and circulatory loop of the liver and the gut has attracted significant attention regarding the role of the microbiota in the development and progression of liver disease. Here we give an overview of the interaction between the microbiota and the immune system and focus on their convincing role in both the propagation and treatment of liver disease. PMID:26835593

  10. Liver mitochondria and insulin resistance.

    PubMed

    Vial, Guillaume; Dubouchaud, Hervé; Leverve, Xavier M

    2010-01-01

    With a steadily increasing prevalence, insulin resistance (IR) is a major public health issue. This syndrome is defined as a set of metabolic dysfunctions associated with, or contributing to, a range of serious health problems. These disorders include type 2 diabetes, metabolic syndrome, obesity, and non-alcoholic steatohepatitis (NASH). According to the literature in the field, several cell types like β-cell, myocyte, hepatocyte and/or adipocyte, as well as related complex signaling environment involved in peripheral insulin sensitivity are believed to be central in this pathology. Because of the central role of the liver in the whole-body energy homeostasis, liver insulin sensitivity and its potential relationship with mitochondrial oxidative phosphorylation appear to be crucial. The following short review highlights how liver mitochondria could be implicated in IR and should therefore be considered as a specific therapeutic target in the future. PMID:21079817

  11. Liver transplantation for hepatocellular carcinoma

    PubMed Central

    Byam, Jerome; Renz, John

    2013-01-01

    Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is considered an aggressive tumor with mean survival estimated between 6 and 20 months. Hepatitis B and C are the most common etiologies. Pathological, laboratory and radiologic imaging all aid in diagnosis but much controversy exists in the utilization of any given modality. Many treatment options exist for management of HCC, each has its own limitation. Liver transplantation offers the most reasonable expectation for curative treatment while simultaneously removing the burden of the diseased liver. Still, advancements in the field have thus far not yet matched its potential, although new immunosuppressive and chemotherapy regimen may allow transplantation to push the envelope once again. PMID:24570911

  12. Treatment of alcoholic liver disease

    PubMed Central

    Frazier, Thomas H.; Stocker, Abigail M.; Kershner, Nicole A.; Marsano, Luis S.; McClain, Craig J.

    2011-01-01

    Alcoholic liver disease (ALD) remains a major cause of liver-related mortality in the US and worldwide. The correct diagnosis of ALD can usually be made on a clinical basis in conjunction with blood tests, and a liver biopsy is not usually required. Abstinence is the hallmark of therapy for ALD, and nutritional therapy is the first line of therapeutic intervention. The role of steroids in patients with moderate to severe alcoholic hepatitis is gaining increasing acceptance, with the caveat that patients be evaluated for the effectiveness of therapy at 1 week. Pentoxifylline appears to be especially effective in ALD patients with renal dysfunction/hepatorenal syndrome. Biologics such as specific anti-TNFs have been disappointing and should probably not be used outside of the clinical trial setting. Transplantation is effective in patients with end-stage ALD who have stopped drinking (usually for ≥6 months), and both long-term graft and patient survival are excellent. PMID:21317995

  13. LIVER REGENERATION: ALTERNATIVE EPITHELIAL PATHWAYS

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    Loss of hepatic tissue triggers a regenerative response in the whole organ. Under typical normal conditions, all hepatic cells (epithelial: hepatocytes and biliary epithelial cells; non-epithelial: stellate cells, macrophages and endothelial cells) undergo one to three rounds of replication to establish the original number of cells and restore organ size. The review summarizes the literature of regenerative patterns in situations in which proliferation of either hepatocytes or biliary epithelial cells is inhibited. The evidence strongly suggests that under these circumstances, hepatocytes or biliary epithelial cells can function as facultative stem cells for each other and replenish the inhibited cellular compartment by a process of trans-differentiation, involving complex signaling pathways. These pathways are activated under experimental conditions in rodents and in fulminant hepatitis associated with liver failure in humans. Mechanistic analysis of these pathways has implications for liver biology and for potential therapeutic modalities in human liver disease. PMID:19788929

  14. Multicystic Hepatocarcinoma Mimicking Liver Abscess

    PubMed Central

    Falidas, Evangelos; Pazidis, Angelos; Anyfantakis, Georgios; Vlachos, Konstantinos; Goudeli, Christina; Villias, Constantinos

    2013-01-01

    The diagnosis of hepatocellular carcinoma (HCC) became easier in relation to the improved radiological examinations; however, the neoplasm may occur under atypical presentations mimicking other benign or malignant processes. Multicystic HCC mimicking a liver abscess associated with septic-type fever and leukocytosis is rare, has a poor prognosis, and poses diagnostic and therapeutic dilemmas. We present the case of an 80-year-old patient, who presented with fever, leukocytosis, and large cystic masses involving right and left lobes of the liver initially considered abscesses and finally diagnosed as HCC after open drainage and liver biopsy. Although the patient died on the tenth postoperative day due to pulmonary oedema, the authors emphasize the high index of suspicion needed in the diagnosis of this unusual presentation of HCC. PMID:23365779

  15. [Syphilis hepatitis and liver transplantation].

    PubMed

    Camara, B; Kamar, N; Bonafe, J-L; Danjoux, M; Suc, B; Rostaing, L

    2007-02-01

    We report a case of secondary syphilis hepatitis in a liver-transplant patient. This homosexual male patient presented, 15 years after orthotopic liver transplantation, with non-squamous papulomacular rash, mild cytolysis, and anicteric cholestasis. Laboratory tests showed syphilis seroconversion with a venereal diseases research laboratory (VDRL) titer of 1/256, a Treponema pallidum hemaglutination assay (TPHA) of 1/5120, and a positive IgM fluorescent Treponemal antibody absorbance (FTA-abs). A liver biopsy performed 13 months after the diagnosis showed low-grade hepatitis with a Metavir score of A1F1; it also showed non-specific portal moderate inflammation consisting primarily of neutrophils, with no evidence of cholestasis. He was given benzathine-penicillin at 2,400,000 IU with a transient increase in prednisolone doses. Cytolysis rapidly, and cholestasis progressively disappeared. IgM FTA-abs became negative, whereas VDRL and TPHA titers decreased slightly over time. PMID:17270378

  16. [Primary lipoma of the liver].

    PubMed

    Bornstein-Quevedo, L; Avilés-Salas, A; Laguna, M; Mercado, M A; Gamboa-Domínguez, A

    2000-01-01

    A case of lipoma of the liver is reported in a 57-year-old woman with a 10-month history of non-insulin dependent diabetes mellitus and 3 days with abdominal pain, distention, nausea, and vomiting. On medical examination, the liver was palpable 5 cm below the right costal margin without splenomegaly or ascites. A CT scan revealed a well-defined fat attenuation tumor and an MR demonstrated a well-circumscribed lesion with bright signal intensity. An extended right hepatic lobectomy was performed. The resected specimen measured 28.6 x 18.3 x 8.2 cm and weighed 2,200 g. The yellow and well-circumscribed tumor measured 15 x 9.5 cm and was composed of mature adipose cells pushing the liver tissue at the periphery. The patient was asymptomatic 6 months after surgery. PMID:11464613

  17. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  18. Hepatitis C and liver transplantation

    NASA Astrophysics Data System (ADS)

    Brown, Robert S.

    2005-08-01

    Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

  19. [Ultrasonic diagnosis of liver diseases].

    PubMed

    Brügmann, E; von Annen, K ,

    1990-07-01

    Sonography has become widely used in the diagnosis of liver diseases. Fatty infiltration of the liver (adiposis hepatica), hepatic cirrhosis, cysts, metastases and tumors can be reliably diagnosed. A valid differentiation between benign and malignant new growths, however, can only be obtained by cytologic and histologic techniques. The lowest sensitivity can be expected in chronical benign diffuse diseases. Our results were compared with those in literature. Furthermore, other diagnostic approaches and procedures, e.g. fine needle biopsy and sclerotherapy in cysts, are recorded. PMID:2232633

  20. CHIMERISM AND LIVER TRANSPLANT TOLERANCE

    PubMed Central

    Mineo, Davide; Ricordi, Camillo

    2008-01-01

    Chimerism and tolerance in a recipient of a deceased-donor liver transplant. Alexander SI, Smith N, Hu M, Verran D, Shun A, Dorney S, Smith A, Webster B, Shaw PJ, Lammi A, Stormon MO. Complete hematopoietic chimerism and tolerance of a liver allograft from a deceased male donor developed in a 9-year-old girl, with no evidence of graft-versus-host disease 17 months after transplantation. The tolerance was preceded by a period of severe hemolysis, reflecting partial chimerism that was refractory to standard therapies. The hemolysis resolved after the gradual withdrawal of all immunosuppressive therapy. PMID:18644653

  1. Liver transplantation in alcoholic liver disease current status and controversies

    PubMed Central

    Singal, Ashwani K; Chaha, Khushdeep S; Rasheed, Khalid; Anand, Bhupinderjit S

    2013-01-01

    Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids. PMID:24106395

  2. Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects.

    PubMed

    Telles-Correia, Diogo; Mega, Inês

    2015-10-21

    In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease (ALD). In the United States, this percentage is 17.2%. Post-transplant survival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, non-adherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment. PMID:26494959

  3. Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects

    PubMed Central

    Telles-Correia, Diogo; Mega, Inês

    2015-01-01

    In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease (ALD). In the United States, this percentage is 17.2%. Post-transplant survival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, non-adherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment. PMID:26494959

  4. Clinical implications of advances in liver regeneration

    PubMed Central

    Kwon, Yong Jin; Lee, Kyeong Geun

    2015-01-01

    Remarkable advances have been made recently in the area of liver regeneration. Even though liver regeneration after liver resection has been widely researched, new clinical applications have provided a better understanding of the process. Hepatic damage induces a process of regeneration that rarely occurs in normal undamaged liver. Many studies have concentrated on the mechanism of hepatocyte regeneration following liver damage. High mortality is usual in patients with terminal liver failure. Patients die when the regenerative process is unable to balance loss due to liver damage. During disease progression, cellular adaptations take place and the organ microenvironment changes. Portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy are relatively recent techniques exploiting the remarkable progress in understanding liver regeneration. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another major clinical field involving liver regeneration is cell therapy using adult stem cells. The aim of this article is to provide an outline of the clinical approaches being undertaken to examine regeneration in liver diseases. PMID:25834796

  5. [Liver parameters in intensive care medicine].

    PubMed

    Penndorf, V; Saner, F; Gerken, G; Canbay, A

    2013-12-01

    Elevated liver function tests in ICU-bound patients are associated with a greater risk of mor-tality. Chronic liver diseases as well as acute events and complications of therapy are among the causes. The disorder could further be investigated by assessment of liver cell integrity markers (AST, ALT and GLDH), cholestasis parameters -(bilirubin, GGT, ALP) and liver synthethic function (albumin, coagulation profile). Ultrasound and elastography are cheap and mobile options to evaluate chronic liver disease, cholestasis or perfusion of the liver. The interpretation of the results should include the medical history on the ICU. Liver injury could be due to septic or isch-aemic complications as well as toxic side effects or parenteral nutrition. The main therapeutic option is to identify the cause of the liver dysfuntion and to eliminate it as far as possible. PMID:22565500

  6. More People Surviving Sudden Liver Failure

    MedlinePlus

    ... fullstory_158123.html More People Surviving Sudden Liver Failure Better diagnosis and care may be behind the ... HealthDay News) -- The chances of surviving acute liver failure have improved significantly over the past 16 years, ...

  7. Platelet-Derived Serotonin Mediates Liver Regeneration

    NASA Astrophysics Data System (ADS)

    Lesurtel, Mickael; Graf, Rolf; Aleil, Boris; Walther, Diego J.; Tian, Yinghua; Jochum, Wolfram; Gachet, Christian; Bader, Michael; Clavien, Pierre-Alain

    2006-04-01

    The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.

  8. When Your Child Needs a Liver Transplant

    MedlinePlus

    ... 1-antitrypsin, leading to lung and liver damage hemochromatosis : an inherited disease that causes the body to ... Anesthesia Preparing Your Child for Surgery Hepatitis Hereditary Hemochromatosis Digestive System Blood Test: Hepatic (Liver) Function Panel ...

  9. Inherited liver diseases in adults.

    PubMed Central

    Kumar, A; Riely, C A

    1995-01-01

    Important inherited disorders causing acute and chronic liver disease include hemochromatosis, Wilson's disease, alpha 1-antiprotease (antitrypsin) deficiency, and cystic fibrosis. The detection of an index case has implications for screening family members. A normal life span can be expected with treatment in asymptomatic patients with Wilson's disease and hemochromatosis. We present a clinical approach to disease recognition, investigation, and screening. PMID:7483606

  10. Adaptive immunity in the liver

    PubMed Central

    Shuai, Zongwen; Leung, Miranda WY; He, Xiaosong; Zhang, Weici; Yang, Guoxiang; Leung, Patrick SC; Eric Gershwin, M

    2016-01-01

    The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver. PMID:26996069

  11. Adaptive immunity in the liver.

    PubMed

    Shuai, Zongwen; Leung, Miranda Wy; He, Xiaosong; Zhang, Weici; Yang, Guoxiang; Leung, Patrick Sc; Eric Gershwin, M

    2016-05-01

    The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver. PMID:26996069

  12. Liver Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  13. Multidisciplinary imaging of liver hydatidosis.

    PubMed

    Marrone, Gianluca; Crino', Francesca; Caruso, Settimo; Mamone, Giuseppe; Carollo, Vincenzo; Milazzo, Mariapina; Gruttadauria, Salvatore; Luca, Angelo; Gridelli, Bruno

    2012-04-01

    Liver hydatidosis is a parasitic endemic disease affecting extensive areas in our planet, a significant stigma within medicine to manage because of its incidence, possible complications, and diagnostic involvements. The diagnosis of liver hydatidosis should be as fast as possible because of the relevant complications that may arise with disease progression, involving multiple organs and neighboring structures causing disruption, migration, contamination. The aim of this essay is to illustrate the role of imaging as ultrasonography (US), multi detector row computed tomography, and magnetic resonance imaging (MRI) in the evaluation of liver hydatidosis: the diagnosis, the assessment of extension, the identification of possible complications and the monitoring the response to therapy. US is the screening method of choice. Computed tomography (CT) is indicated in cases in which US is inadequate and has high sensitivity and specificity for calcified hydatid cysts. Magnetic resonance is the best imaging procedure to demonstrate a cystic component and to show a biliary tree involvement. Diagnostic tests such as CT and MRI are mandatory in liver hydatidosis because they allow thorough knowledge regarding lesion size, location, and relations to intrahepatic vascular and biliary structures, providing useful information for effective treatment and decrease in post-operative morbidity. Hydatid disease is classified into four types on the basis of their radiologic appearance. PMID:22509075

  14. Pharmacotherapy of cholestatic liver diseases.

    PubMed

    Paumgartner, Gustav

    2010-06-01

    New insights into the molecular mechanisms of bile formation and cholestasis have provided new concepts for pharmacotherapy of cholestatic liver diseases. The major aim in all forms of cholestasis is the reduction of hepatocellular retention of bile acids and other potentially toxic constituents of bile. Reduction of hepatocellular retention may be achieved by drugs that stimulate hepatocellular secretion via the canalicular route into the bile or via the alternative route across the basolateral membrane into the blood, and by drugs that stimulate the hepatocellular metabolism of hydrophobic bile acids to hydrophilic, less toxic metabolites. In cholestatic liver diseases that start with an injury of the biliary epithelium (e.g., primary biliary cirrhosis; PBC), protection of the cholangiocytes against the toxic effects of hydrophobic bile acids is most important. When hepatocellular retention of bile acids has occurred, the inhibition of bile acid-induced apoptosis becomes another target of therapy. Ursodeoxycholic acid protects the biliary epithelium by reducing the toxicity of bile, stimulates hepatobiliary secretion by upregulating transporters and inhibits apoptosis. It is the mainstay of therapy in PBC but of benefit also in a number of other cholestatic liver diseases. New drugs such as 6-ethyl-chenodeoxycholic acid and 24-nor-ursodeoxycholic acid are being evaluated for the treatment of cholestatic liver diseases. PMID:20579215

  15. Pregnancy and Vascular Liver Disease

    PubMed Central

    Bissonnette, Julien; Durand, François; de Raucourt, Emmanuelle; Ceccaldi, Pierre-François; Plessier, Aurélie; Valla, Dominique; Rautou, Pierre-Emmanuel

    2015-01-01

    Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd–Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown. In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation. PMID:25941432

  16. Liver disease in cystic fibrosis.

    PubMed

    Colombo, Carla; Russo, Maria Chiara; Zazzeron, Laura; Romano, Giovanna

    2006-07-01

    Liver involvement in Cystic Fibrosis (CF) is much less frequent than both pulmonary and pancreatic diseases that are present in 80-90% of CF patients; liver disease (LD) affects only one third of CF patients, however, because of the decreasing mortality from extrahepatic causes, its recognition and management is becoming a relevant clinical issue. Recent observations suggest that clinical expression of LD in CF may be influenced by genetic modifiers; their identification is an important issue because it may allow recognition of patients at risk for the development of LD at the time of diagnosis of CF and early institution of prophylactic strategies. Oral bile acid therapy, aimed at improving biliary secretion in terms of bile viscosity and bile acid composition, is currently the only available therapeutic approach for CF-associated LD. However, the impact of this therapy on the natural history of LD remains to be defined and long-term effectiveness on clinically relevant outcomes should be further investigated. Liver transplantation should be offered to CF patients with progressive liver failure and/or with life-threatening sequelae of portal hypertension, who also have mild pulmonary involvement that is expected to support long-term survival. The 1-year survival rate after transplantation in CF patients is approximately 80%, with beneficial effects on lung function, nutritional status, body composition and quality of life in most cases. PMID:16819402

  17. Urea Biosynthesis Using Liver Slices

    ERIC Educational Resources Information Center

    Teal, A. R.

    1976-01-01

    Presented is a practical scheme to enable introductory biology students to investigate the mechanism by which urea is synthesized in the liver. The tissue-slice technique is discussed, and methods for the quantitative analysis of metabolites are presented. (Author/SL)

  18. Kidneys in chronic liver diseases

    PubMed Central

    Hartleb, Marek; Gutkowski, Krzysztof

    2012-01-01

    Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support. PMID:22791939

  19. Kupffer Cells in the Liver

    PubMed Central

    Dixon, Laura J.; Barnes, Mark; Tang, Hui; Pritchard, Michele T.; Nagy, Laura E.

    2016-01-01

    Kupffer cells are a critical component of the mononuclear phagocytic system and are central to both the hepatic and systemic response to pathogens. Kupffer cells are reemerging as critical mediators of both liver injury and repair. Kupffer cells exhibit a tremendous plasticity; depending on the local metabolic and immune environment, then can express a range of polarized phenotypes, from the proinflammatory M1 phenotype to the alternative/M2 phenotype. Multiple M2 phenotypes can be distinguished, each involved in the resolution of inflammation and wound healing. Here, we have provided an update on recent research that has contributed to the developing delineation of the contribution of Kupffer cells to different types of liver injury, with an emphasis on alcoholic and nonalcoholic liver diseases. These recent advances in our understanding of Kupffer cell function and regulation will likely provide new insights into the potential for therapeutic manipulation of Kupffer cells to promote the resolution of inflammation and enhance wound healing in liver disease. PMID:23720329

  20. Pregnancy and vascular liver disease.

    PubMed

    Bissonnette, Julien; Durand, François; de Raucourt, Emmanuelle; Ceccaldi, Pierre-François; Plessier, Aurélie; Valla, Dominique; Rautou, Pierre-Emmanuel

    2015-03-01

    Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd-Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown. In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation. PMID:25941432

  1. Multimodal Phantom of Liver Tissue

    PubMed Central

    Chmarra, Magdalena K.; Hansen, Rune; Mårvik, Ronald; Langø, Thomas

    2013-01-01

    Medical imaging plays an important role in patients' care and is continuously being used in managing health and disease. To obtain the maximum benefit from this rapidly developing technology, further research is needed. Ideally, this research should be done in a patient-safe and environment-friendly manner; for example, on phantoms. The goal of this work was to develop a protocol and manufacture a multimodal liver phantom that is suitable for ultrasound, computed tomography, and magnetic resonance imaging modalities. The proposed phantom consists of three types of mimicked soft tissues: liver parenchyma, tumors, and portal veins, that are made of six ingredients: candle gel, sephadex®, agarose, glycerol, distilled water, and silicone string. The entire procedure is advantageous, since preparation of the phantom is simple, rather cost-effective, and reasonably quick – it takes around 2 days. Besides, most of the phantom's parts can be reused to manufacture a new phantom. Comparison of ultrasound images of real patient's liver and the developed phantom shows that the phantom's liver tissue and its structures are well simulated. PMID:23691165

  2. Predictive Models of Liver Cancer

    EPA Science Inventory

    Predictive models of chemical-induced liver cancer face the challenge of bridging causative molecular mechanisms to adverse clinical outcomes. The latent sequence of intervening events from chemical insult to toxicity are poorly understood because they span multiple levels of bio...

  3. Therapeutic targets in liver fibrosis.

    PubMed

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points. PMID:21233278

  4. New Concepts in Liver Regeneration

    PubMed Central

    Riehle, Kimberly J.; Dan, Yock Young; Campbell, Jean S.; Fausto, Nelson

    2011-01-01

    The unique ability of the liver to regenerate itself has fascinated biologists for years and has made it the prototype for mammalian organ regeneration(1–3). Harnessing this process has great potential benefit in the treatment of liver failure and has been the focus of intense research over the past 50 years. Not only will detailed understanding of cell proliferation in response to injury be applicable to other dysfunction of organs, it may also shed light on how cancer develops in a cirrhotic liver, in which there is intense pressure on cells to regenerate. Advances in molecular techniques over the past few decades have led to the identification of many regulatory intermediates, and pushed us onto the verge of an explosive era in regenerative medicine. To date, more than 10 clinical trials have been reported in which augmented regeneration using progenitor cell therapy has been attempted in human patients(4). This review traces the path that has been taken over the last few decades in the study of liver regeneration, highlights new concepts in the field, and the challenges that still stand between us and clinical therapy. PMID:21199532

  5. Management in Acute Liver Failure

    PubMed Central

    Shalimar; Acharya, Subrat K.

    2015-01-01

    Acute liver failure (ALF) is a rare, potentially fatal complication of severe hepatic illness resulting from various causes. In a clinical setting, severe hepatic injury is usually recognised by the appearance of jaundice, encephalopathy and coagulopathy. The central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a central role in the pathogenesis. The role of newer ammonia lowering agents is still evolving. Liver transplant is the only effective therapy that has been identified to be of promise in those with poor prognostic factors, whereas in the others, aggressive intensive medical management has been documented to salvage a substantial proportion of patients. A small fraction of patients undergo liver transplant and the remaining are usually treated with medical therapy. Therefore, identification of the complications and causes of death in such patients, and use of appropriate prognostic models to identify those who need liver transplant and those who can be managed with medical treatment is a vital component of therapeutic strategy. In this review, we discuss the various pathogenetic mechanisms and treatment options available. PMID:26041950

  6. Renal dysfunction associated with liver transplantation.

    PubMed Central

    Jindal, R. M.; Popescu, I.

    1995-01-01

    It has been known for some time that a variety of liver diseases affect kidney function, but renal dysfunction associated with orthotopic liver transplantation has received scant attention. Although the mechanisms mediating these abnormalities are incompletely defined, advances in the understanding of renal pathophysiology after liver transplantation have made it possible to develop new treatment strategies. Aggressive and early intervention to diagnose and treat renal complications associated with liver transplantation should be the goal for transplant centres. PMID:7479462

  7. Role of liver stem cells in hepatocarcinogenesis

    PubMed Central

    Xu, Lei-Bo; Liu, Chao

    2014-01-01

    Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the “cancer stem cell hypothesis”, which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future. PMID:25426254

  8. Therapy for alcoholic liver disease

    PubMed Central

    Jaurigue, Maryconi M; Cappell, Mitchell S

    2014-01-01

    Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation. PMID:24605013

  9. Transcriptional Ontogeny of the Developing Liver

    EPA Science Inventory

    During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hemato...

  10. Isolation and characterization of chicken liver lysosomes.

    PubMed

    Nakabayashi, T; Ikezawa, H

    1988-06-01

    The distribution patterns of chicken liver lysosomal enzymes were studied in iso-osmotic gradients of Percoll. The lysosomal enzymes separated by Percoll gradients showed three different types of distribution. In contrast with rat liver lysosomes, purified chicken liver lysosomes were very stable during storage at 4 degrees C. PMID:2845991

  11. Chronic hepatitis C and liver fibrosis

    PubMed Central

    Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy. PMID:25170193

  12. Plasma Glutamine Concentrations in Liver Failure

    PubMed Central

    Helling, Gunnel; Wahlin, Staffan; Smedberg, Marie; Pettersson, Linn; Tjäder, Inga; Norberg, Åke; Rooyackers, Olav; Wernerman, Jan

    2016-01-01

    Background Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations. Methods Four different groups of patients were studies; chronic liver failure (n = 40), acute on chronic liver failure (n = 20), acute fulminant liver failure (n = 20), and post-hepatectomy liver failure (n = 20). Child-Pugh and Model for End-stage Liver Disease (MELD) scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion. Results All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100), severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong. Conclusion Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure. PMID:26938452

  13. Blood flukes (Digenea: Aporocotylidae) infecting body cavity of South American catfishes (Siluriformes: Pimelodidae): two new species from rivers in Bolivia, Guyana and Peru with a re-assessment of Plehniella Szidat, 1951.

    PubMed

    Orelis-Ribeiro, Raphael; Bullard, Stephen A

    2015-01-01

    Plehniella Szidat, 1951 is emended based on new collections from South American long-whiskered catfishes. It is clearly differentiated from Sanguinicola Plehn, 1905 by lacking lateral tegumental body spines and by having 6 asymmetrical caeca. Plehniella sabajperezi sp. n. infects body cavity of Pimelodus albofasciatus (Mees) from the Demerara and Rupununi Rivers (Guyana) and Pimelodus blochii (Valenciennes) from Lake Tumi Chucua (Bolivia) and Napo River (Peru). It differs from Plehniella coelomicola Szidat, 1951 (type species) by having a thin-walled vas deferens that greatly exceeds the length of cirrus-sac and that joins the cirrus-sac at level of ovovitelline duct and ootype, an internal seminal vesicle that is absent or diminutive, and a cirrus-sac that is spheroid, nearly marginal, and envelops the laterally-directed distal portion of the male genitalia. Plehniella armbrusteri sp. n. infects body cavity of P. blochii from Lake Tumi Chucua (Bolivia). It differs from P. coelomicola and P. sabajperezi by having a relatively ovoid body, a massive intestine comprising caeca that are deeply-lobed to diverticulate and terminate in the posterior half of the body, a testis that flanks the distal tips of the posteriorly-directed caeca, and a proximal portion of the vas deferens that loops ventral to the testis. Small adults (Plehniella sp.) collected from body cavity of Pimelodus grosskopfii (Steindachner) from Cienega de Jobo and Canal del Dique (Colombia) differ from congeners by having a posteriorly-constricted body region, an anterior sucker with concentric rows of minute spines, an elongate anterior oesophageal swelling, short and wide caeca, and a male genital pore that opens proportionally more anteriad. This study nearly doubles the number of aporocotylids documented from South America Rivers and comprises the first record of a fish blood fluke from P. blochii, P. albofasciatus and P. grosskopfii as well as from Bolivia, Colombia, Guyana or Peru. PMID:26373332

  14. The Pathology of Acute Liver Failure.

    PubMed

    Lefkowitch, Jay H

    2016-05-01

    Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells. This paper reviews the liver pathology in ALF, including forms of zonal necrosis and their etiologies. PMID:27058243

  15. Nonalcoholic Fatty Liver Disease and Psoriasis

    PubMed Central

    Prussick, Lisa; Nussbaum, Dillon

    2015-01-01

    Psoriasis is a systemic inflammatory disease associated with a variety of comorbidities. It has been shown that psoriasis patients have an increased incidence of nonalcoholic fatty liver disease over controls. Patients with nonalcoholic fatty liver disease and psoriasis have more severe skin disease and are at higher risk of severe liver fibrosis than patients without psoriasis. The authors will review the diagnosis of nonalcoholic fatty liver disease and also discuss lifestyle changes and treatments for psoriasis that may benefit or worsen nonalcoholic fatty liver disease. PMID:25852814

  16. Paracetamol, alcohol and the liver

    PubMed Central

    Prescott, Laurie F

    2000-01-01

    It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports where it is alleged that paracetamol hepatotoxicity was enhanced in chronic alcoholics, the reverse should have been the case because alcohol was actually taken at the same time as the paracetamol. Chronic alcoholics are likely to be most vulnerable to the toxic effects of paracetamol during the first few days of withdrawal but maximum therapeutic doses given at this time have no adverse effect on liver function tests. Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insufficient evidence to support the alleged major toxic interaction. It is astonishing that clinicians and others have unquestion-ingly accepted this supposed interaction in man for so long with such scant regard for scientific objectivity. PMID:10759684

  17. Liver bioengineering: Current status and future perspectives

    PubMed Central

    Booth, Christopher; Soker, Tom; Baptista, Pedro; Ross, Christina L; Soker, Shay; Farooq, Umar; Stratta, Robert J; Orlando, Giuseppe

    2012-01-01

    The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes. There are two general pathways to liver bioengineering and regeneration. The first consists of creating a supporting scaffold, either synthetically or by decellularization of human or animal organs, and seeding cells on the scaffold, where they will mature either in bioreactors or in vivo. This strategy seems to offer the quickest route to clinical translation, as demonstrated by the development of liver organoids from rodent livers which were repopulated with organ specific cells of animal and/or human origin. Liver bioengineering has potential for transplantation and for toxicity testing during preclinical drug development. The second possibility is to induce liver regeneration of dead or resected tissue by manipulating cell pathways. In fact, it is well known that the liver has peculiar regenerative potential which allows hepatocyte hyperplasia after amputation of liver volume. Infusion of autologous bone marrow cells, which aids in liver regeneration, into patients was shown to be safe and to improve their clinical condition, but the specific cells responsible for liver regeneration have not yet been determined and the underlying mechanisms remain largely unknown. A complete understanding of the cell pathways and dynamics and of the functioning of liver stem cell niche is necessary for the clinical translation of regenerative medicine strategies. As well, it will be crucial to elucidate the mechanisms through which cells interact with the extracellular matrix, and how this latter supports and drives cell fate. PMID:23322990

  18. Quantification of liver fat: A comprehensive review.

    PubMed

    Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

    2016-04-01

    Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. PMID:26945465

  19. Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma

    PubMed Central

    Palmer, William C.; Patel, Tushar

    2012-01-01

    Background & Aims Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most patients in Western countries. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions. Methods We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated. Results Eleven studies from both high and low prevalence regions were identified. All studies except for those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI = 18.24 28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.918.95), hepatitis C: 4.84 (2.419.71), obesity: 1.56 (1.261.94), diabetes mellitus type II: 1.89 (1.742.07), smoking: 1.31 (0.951.82), and alcohol use: 2.81 (1.525.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias. Conclusions Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers. PMID:22420979

  20. Human immunodeficiency virus infection and the liver

    PubMed Central

    Crane, Megan; Iser, David; Lewin, Sharon R

    2012-01-01

    Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries. PMID:22489261

  1. Chemotherapy induced liver abnormalities: an imaging perspective

    PubMed Central

    Houshyar, Roozbeh; Bhosale, Priya; Choi, Joon-Il; Gulati, Rajesh; Lall, Chandana

    2014-01-01

    Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy. PMID:25320738

  2. Protective Effect of Salep on Liver

    PubMed Central

    Pourahmad, Morteza; Kargar Jahromi, Hossein; Kargar Jahromi, Zahra

    2015-01-01

    Background: Salep is used for various purposes in food industries and traditional medicine. Therefore, evaluation of its effect on the liver seems to be necessary. Objectives: The aim of this study was to assess salep effect on liver. Materials and Methods: In this experimental study, various concentrations of Salep were intraperitoneally administered to five groups of Wistar rats (control, placebo and 20, 40 and 80 mg/kg salep). After one month, liver enzymes and liver tissue were evaluated and compared between different groups. Results: Significant decreased level of liver enzymes, MDA (Malondialdehyde) and TOC (Total Oxidation Capacity) were found in various concentrations of salep administration. On the other hand, a significant increase was found in TAC (Total Antioxidant Capacity) level with various doses of salep. Conclusions: Elevated level of total protein and albumin and decreased level of liver enzyme by salep extract were found in this study. Therefore, this plant may be a useful medicine for patients with liver diseases. PMID:26034505

  3. Liver involvement in subjects with rheumatic disease

    PubMed Central

    2011-01-01

    The liver is often overlooked as a target organ, with pathology either secondary to an underlying disease or due to the toxicity of therapies and the medical complications of extrahepatic diseases. It is thus important for the clinical rheumatologist to be aware of the diagnostic procedure to monitor liver injury. Indeed, systemic rheumatologic diseases may be associated with liver abnormalities secondary to the presence of a coexisting autoimmune liver disease (particularly primary biliary cirrhosis or autoimmune hepatitis), the direct involvement of the liver parenchyma, or the impact of medical treatments (particularly methotrexate) on the liver. In addition, the rheumatologist should be aware of the impact of immunosuppressive agents on underlying viral infections, particularly viral hepatitis. We review herein the data on the role of the liver in the clinical management of systemic rheumatic diseases. PMID:21722332

  4. Vitamin E reduces liver stiffness in nonalcoholic fatty liver disease

    PubMed Central

    Fukui, Aiko; Kawabe, Naoto; Hashimoto, Senju; Murao, Michihito; Nakano, Takuji; Shimazaki, Hiroaki; Kan, Toshiki; Nakaoka, Kazunori; Ohki, Masashi; Takagawa, Yuka; Takamura, Tomoki; Kamei, Hiroyuki; Yoshioka, Kentaro

    2015-01-01

    AIM: To evaluate the efficacy of vitamin E treatment on liver stiffness in nonalcoholic fatty liver disease (NAFLD). METHODS: Thirty-eight NAFLD patients were administered vitamin E for > 1 year. The doses of vitamin E were 150, 300, or 600 mg; three times per day after each meal. Responses were assessed by liver enzyme levels [aspartate aminotransferase (AST), alanine aminotranferease (ALT), and γ-glutamyl transpeptidase (γ-GTP)], noninvasive scoring systems of hepatic fibrosis-4 [FIB-4 index and aspartate aminotransferase-to-platelet index (APRI)], and liver stiffness [velocity of shear wave (Vs)] measured by acoustic radiation force impulse elastography. Vs measurements were performed at baseline and 12 mo after baseline. The patients were genotyped for the patatin-like phospholipase domain containing 3 (PNPLA3) polymorphisms and then divided into either the CC/CG or GG group to examine each group’s responses to vitamin E treatment. RESULTS: We found marked differences in the platelet count, serum albumin levels, alkaline phosphatase levels, FIB-4 index, APRI, and Vs at baseline depending on the PNPLA3 polymorphism. AST, ALT, and γ-GTP levels (all P < 0.001); FIB-4 index (P = 0.035); APRI (P < 0.001); and Vs (P < 0.001) significantly decreased from baseline to 12 mo in the analysis of all patients. In the subset analyses of PNPLA3 genotypes, AST levels (P = 0.011), ALT levels (P < 0.001), γ-GTP levels (P = 0.005), APRI (P = 0.036), and Vs (P = 0.029) in genotype GG patients significantly improved, and AST and ALT levels (both P < 0.001), γ-GTP levels (P = 0.003), FIB-4 index (P = 0.017), and APRI (P < 0.001) in genotype CC/CG patients. CONCLUSION: One year of vitamin E treatment improved noninvasive fibrosis scores and liver stiffness in NAFLD patients. The responses were similar between different PNPLA3 genotypes. PMID:26644818

  5. [Microbiology of various liver products].

    PubMed

    Lukásová, J; Steinhauser, L; Suchánek, S

    1979-03-01

    The proportions of mesophilic, thermophilic and psychrophilic microorganisms were investigated in the total number of microbes and aerobic sporogenic microorganisms in delicatessen liver sausages and liver cheeses. At the same time the content of ammonia and the pH of the products were determined. The largest part of the microflora comprised mesophilic microorganisms, 10 to 25% of which belonged to the sporogenic microflora. The incidence of staphylococci, enterococci and coliform microorganisms was also studied. The total number of microbes contributed to the ammonia content in the products, however, no intercorrelation was statistically proved. In the case of pH no relationship between its value and the number or kind of investigated microorganisms was found. All the indicators were followed in the raw material, in the finished products after heat processing and in products stored at refridgerator and room temperatures for one week. PMID:34256

  6. Undifferentiated Embryonal Sarcoma of Liver

    PubMed Central

    Kallam, Avyakta; Krishnamurthy, Jairam; Kozel, Jessica

    2015-01-01

    Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant hepatic tumor. A 47 year old male presented with symptoms of sour taste in his mouth, occasional nausea, indigestion and 15-pound weight loss over two months. He had an unremarkable upper gastrointestinal endoscopy. Imaging showed a large liver mass in the left hepatic lobe that was resected and then reported as UESL. He went on to develop lung metastases and was initially treated with doxorubicin and ifosfamide followed by switching of therapy to gemcitabine and docetaxel due to progression of disease. He had a good response after two cycles and went on to receive four more cycles, achieving stable disease. We can therefore conclude that the combination of gemcitabine and docetaxel is a potential therapeutic option for patients with UESL. PMID:26788276

  7. Undifferentiated Embryonal Sarcoma of Liver.

    PubMed

    Kallam, Avyakta; Krishnamurthy, Jairam; Kozel, Jessica; Shonka, Nicole

    2015-12-29

    Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant hepatic tumor. A 47 year old male presented with symptoms of sour taste in his mouth, occasional nausea, indigestion and 15-pound weight loss over two months. He had an unremarkable upper gastrointestinal endoscopy. Imaging showed a large liver mass in the left hepatic lobe that was resected and then reported as UESL. He went on to develop lung metastases and was initially treated with doxorubicin and ifosfamide followed by switching of therapy to gemcitabine and docetaxel due to progression of disease. He had a good response after two cycles and went on to receive four more cycles, achieving stable disease. We can therefore conclude that the combination of gemcitabine and docetaxel is a potential therapeutic option for patients with UESL. PMID:26788276

  8. [Fractal analysis of liver fibrosis].

    PubMed

    Soda, G; Nardoni, S; Bosco, D; Grizzi, F; Dioguardi, N; Melis, M

    2003-04-01

    This study realized by two different study groups use of Fractal geometry to quantify the complex collagen deposition during chronic liver disease. Thirty standard needle liver biopsy specimens were obtained from patients with chronic HCV-related disease. Three mu-thick sections were cut and stained by means of Picrosirius stain, in order to visualise collagen matrix. The degree of fibrosis was measured using a quantitative scoring system based on the computer-assisted evaluation of the fractal dimension of the deposited collagen surface. The obtained results by both study groups, show that the proposed method is reproducible, rapid and inexpensive. The complex distribution of its collagenous components can be quantified using a single numerical score. This study demonstrated that it is possible to quantify the collagen's irregularity in an objective manner, and that the study of the fractal properties of the collagen shapes is likely to reveal more about its structure and the complex behaviour of its development. PMID:12768879

  9. Liver transplantation. The pediatric challenge.

    PubMed

    McDiarmid, S V

    2000-11-01

    Successful liver transplantation in a child is often a hard-won victory, requiring all the combined expertise of a dedicated pediatric transplant team. This article outlines the considerable challenges still facing pediatric liver transplant physicians and surgeons. In looking to the future, where should priorities lie to enhance the success already achieved? First, solutions to the donor shortage must be sought aggressively by increasing the use of from split-liver transplants, judicious application of living-donor programs, and increasing the donation rate, perhaps by innovative means. The major immunologic barriers, to successful xenotransplantation make it unlikely that this option will be tenable in the near future. Second, current immunosuppression is nonspecific, toxic, and unable to be individually adjusted to the patient's immune response. The goal of achieving donor-specific tolerance will require new consideration of induction protocols. Developing a clinically applicable method to measure the recipient's immunoreactivity is of paramount importance, for future studies of new immunosuppressive strategies and to address the immediate concern of long-term over-immunosuppression. The inclusion of pediatric patients in new protocols will require the ongoing insistence of pediatric transplant investigators. Third, the current immunosuppressive drugs have a long-term morbidity and mortality of their own. These long-term effects are particularly important in children who may well have decades of exposure to these therapies. There is now some understanding of their long-term renal toxicity and the risk of malignancy. New drugs may obviate renal toxicity, whereas the risk of malignancy is inherent in any nonspecific immunosuppressive regimen. Although progress is being made in preventing and recognizing PTLD, this entity remains an important ongoing concern. The global effect of long-term immunosuppression on the child's growth, development, and intellectual potential is unknown. Of particular concern is the potential for neurotoxicity from the calcineurin inhibitors. Fourth, recurrent disease and new diseases, perhaps potentiated by immunosuppressive drugs, must be considered. Already the recurrence of autoimmune disease and cryptogenic cirrhosis have been documented in pediatric patients. Now, a new lesion, a nonspecific hepatitis, sometimes with positive autoimmune markers, that may progress to cirrhosis has been recognized. It is not known whether this entity is an unusual form of rejection, an unrecognized viral infection, or a response to immunosuppressive drugs themselves. Finally, pediatric transplant recipients, like any other children, must be protected and nourished physically and mentally if they are to fulfill their potential. After liver transplantation the child's growth, intellectual functioning, and psychologic adaptation may all require special attention from parents, teachers, and physicians alike. There is limited understanding of how the enormous physical intervention of a liver transplantation affects a child's cognitive and psychologic function as the child progresses through life. The persons caring for these children have the difficult responsibility of providing services to evaluate these essential measures of children's health over the long term and to intervene if necessary. Part of the transplant physician's our duty to protect and advocate for children is to fight for equal access to health care. In most of the developing world, economic pressures make it impossible to consider liver transplantation a health care priority. In the United States and in other countries with the medical infrastructure to support liver transplantation, however, health care professionals must strive to be sure that the policies governing candidacy for transplantation and allocation of organs are applied justly and uniformly to all children whose lives are threatened by liver disease. In the current regulatory climate that increasingly takes medical decisions out of the hands of physicians, pediatricians must be even more prepared to protect the unique and often complicated needs of children both before and after transplantation. Only in this way can the challenges of the present and the future be met. PMID:11232362

  10. Evolving therapies for liver fibrosis

    PubMed Central

    Schuppan, Detlef; Kim, Yong Ook

    2013-01-01

    Fibrosis is an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. With protracted damage, fibrosis can progress toward excessive scarring and organ failure, as in liver cirrhosis. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development, with enormous potential but also high risks. Preclinical research has yielded numerous targets for antifibrotic agents, some of which have entered early-phase clinical studies, but progress has been hampered due to the relative lack of sensitive and specific biomarkers to measure fibrosis progression or reversal. Here we focus on antifibrotic approaches for liver that address specific cell types and functional units that orchestrate fibrotic wound healing responses and have a sound preclinical database or antifibrotic activity in early clinical trials. We also touch upon relevant clinical study endpoints, optimal study design, and developments in fibrosis imaging and biomarkers. PMID:23635787

  11. Surgical accreditation in liver transplantation.

    PubMed

    Casanova, D

    2009-04-01

    Almost 25 years since the first liver transplantation was performed in Spain, 25 groups support the activities of >1000 transplantations a year. Despite such a significant number, it is necessary to initiate mechanisms of accreditation for programs and surgeons. Professional competence in medical care is defined as "the aptitude of the professionals for integrating and applying the knowledge, skills, and attitudes associated with the good practices of their profession." Accreditation is the process by which a professional or a training specialist achieves or satisfies a level of competence and quality. Certification consists of the recognition of an institution where a person has completed a process of accreditation. The Division of Transplantation was formed in 2007 from the Section of Surgery of the Union Europeëne des Medecins Spécialistes (UEMS) and the European Board of Surgery (EBS). The Division operates in close collaboration with the European Society of Organ Transplantation (ESOT). The main objective of the Division is to guarantee the best standard of care in organ transplantation in Europe by ensuring that training in transplantation surgery is maintained at the highest level. Certification can be obtained for the following separate modules: multi-organ retrieval, kidney transplantation, pancreas transplantation, and liver transplantation. The Diploma of the European Board of Surgery Qualification (Transplantation) is obtained by passing Part I (Eligibility) and Part II (Examination). A candidate can be accredited for one or more modules. To obtain accreditation for the liver transplantation module, it is mandatory to obtain accreditation in module 1 as well. The UEMS, through its Medical Committees, offers the opportunity to provide the first steps toward accreditation of training in liver transplantation. PMID:19376409

  12. Radiofrequency Ablation Beyond the Liver

    PubMed Central

    Neeman, Ziv; Wood, Bradford J.

    2008-01-01

    Radiofrequency ablation (RFA) has begun to show promise for extrahepatic indications. Although much of the reported work on image-guided RFA of liver neoplasms is quite promising, it is even earlier in the evaluation and validation process for extrahepatic RFA, with few short-term and no long-term studies reported. Although there are much more data for liver RFA with almost 3,000 cases reported in the literature, there are a number of ongoing investigations of RFA for tumors in the kidney, lung, bone, breast, bone, and adrenal gland. Debulking and pain control with RFA present palliative options becoming increasingly popular weapons in the interventionalist's oncology arsenal. Metastatic disease with a wide variety of primary histologies in a myriad of locations may be treated with RFA after a careful consideration of the risk-to-benefit ratio balance. The RFA technique can be slightly different outside the liver. Specifically, differing dielectric tissue characteristics may markedly alter the RFA treatment. Each different RFA system has a unique risk and advantage profile. Extrahepatic indications and contraindications will be suggested. Treatment tips and the unique complications and considerations will be introduced for some of the more common extrahepatic locations. PMID:12524646

  13. Gastrointestinal dysfunction in liver cirrhosis

    PubMed Central

    Kalaitzakis, Evangelos

    2014-01-01

    Patients with liver cirrhosis exhibit several features of gut dysfunction which may contribute to the development of cirrhosis complications as well as have an impact on nutritional status and health-related quality of life. Gastrointestinal symptoms are common in cirrhosis and their pathophysiology probably involves factors related to liver disease severity, psychological distress, and gut dysfunction (e.g., increased gastric sensitivity to distension and delayed gut transit). They may lead to reduced food intake and, thus, may contribute to the nutritional status deterioration in cirrhotic patients. Although tense ascites appears to have a negative impact on meal-induced accommodation of the stomach, published data on gastric accommodation in cirrhotics without significant ascites are not unanimous. Gastric emptying and small bowel transit have generally been shown to be prolonged. This may be related to disturbances in postprandial glucose, insulin, and ghrelin levels, which, in turn, appear to be associated to insulin resistance, a common finding in cirrhosis. Furthermore, small bowel manometry disturbances and delayed gut transit may be associated with the development of small bowel bacterial overgrowth. Finally, several studies have reported intestinal barrier dysfunction in patients with cirrhosis (especially those with portal hypertension), which is related to bacterial translocation and permeation of intestinal bacterial products, e.g., endotoxin and bacterial DNA, thus potentially being involved in the pathogenesis of complications of liver cirrhosis. PMID:25356031

  14. Hormonal control of liver regeneration

    PubMed Central

    Thrower, Seán; Ord, Margery G.

    1974-01-01

    Two peaks in cyclic AMP production in rat livers 4 and 12h after partial hepatectomy (MacManus et al., 1972) were confirmed and a third peak established at 22h, which is the peak of DNA synthesis. The increases in cyclic AMP were prevented by β-adrenergic blocking agents, propranolol and pindolol, without affecting ornithine decarboxylase induction or DNA synthesis. The α-blocking agents, phenoxybenzamine and phentolamine, given at the time of partial hepatectomy, delayed the rise in ornithine decarboxylase normally found 4h after operation, but did not affect DNA synthesis. If the α-blocking agents were given at 9–12h or 18h, the onset of DNA synthesis was delayed. Phenoxybenzamine did not affect the induction of ornithine decarboxylase in intact rat livers by glucagon or growth hormone, but did inhibit induction by dexamethasone. The induction of ornithine decarboxylase produced by dexamethasone was inhibited by 17α-hydroxy-progesterone; this compound also blocked the induction of ornithine decarboxylase in livers of partially hepatectomized rats. PMID:4156833

  15. Radiofrequence ablation of liver cancers

    PubMed Central

    Liu, Lian-Xin; Jiang, Hong-Chi; Piao, Da-Xun

    2002-01-01

    Primary and secondary malignant liver cancers are some of most common malignant tumors in the world. Chemotherapy and radiotherapy are not very effective against them. Surgical resection has been considered the only potentially curtive option, but the majority of patients are not candidates for resection because of tumor size, location near major intrahepatic blood vessels and bile ducts, precluding a margin-negative resection, cirrhotic, hepatitis virus infection or multifocial. Radiofrequence ablation (RFA), which is a new evolving effective and minimally invasive technique, can produce coagulative necrosis of malignant tumors. RFA should be used percutaneously, laparscopically, or during the open laparotomy under the guidance of ultrasound, CT scan and MRI. RFA has lots of advantages superior to other local therapies including lower complications, reduced costs and hospital stays, and the possibility of repeated treatment. In general, RFA is a safe, effective treatment for unresectable malignant liver tumors less than 7.0 cm in diameter. We review the principle, mechanism, procedures and experience with RFA for treating malignant liver tumors. PMID:12046057

  16. Liver retransplantation for adult recipients

    PubMed Central

    Ahn, Chul-Soo; Kim, Ki-Hun; Moon, Deok-Bog; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

    2013-01-01

    Living donor liver graft can be used for the first or second liver transplantation. The timing of retransplantation also should be stratified as 2 types according to the reoperation timing. Combination of these two classifications results in 6 types of living donor liver transplantation (LDLT)-associated retransplantation. However, late retransplantation to LDLT might have not been performed in most LDLT programs, thus other 4 types of LDLT-associated retransplantation can be taken into account. The most typical type of LDLT-associated retransplantation might be early living donor-to-deceased donor retransplantation. For early living donor-to-living donor retransplantation, its eligibility criteria might be similar to those of early living donor-to-deceased donor retransplantation. For early deceased donor-to-living donor retransplantation, its indications are exactly the same to those for aforementioned living donor-to-living donor retransplantation. Late deceased donor retransplantation after initial LDLT has the same indication for ordinary late deceased donor retransplantation. PMID:26155206

  17. Infectious Complications After Liver Transplantation

    PubMed Central

    Hernandez, Maria Del Pilar; Martin, Paul

    2015-01-01

    Orthotopic liver transplantation (OLT) is the standard of care for patients with decompensated cirrhosis and for patients with hepatocellular carcinoma. More than 6000 liver transplants are performed annually in the United States. High patient and graft survival rates have been achieved in great part due to the availability of potent immunosuppressive agents. Systemic immunosuppression has rendered the liver recipient susceptible to de novo infections as well as reactivation of preexisting latent infections. Infections occurring during the first month post-OLT are usually nosocomial, donor-derived, or the result of a perioperative complication. The development of opportunistic infections (OIs) such as Aspergillus and the reactivation of latent infections such as Mycobacterium tuberculosis are more frequent 1 to 6 months posttransplant, when the net state of immunosuppression is the highest. Immunosuppressive therapy is tapered 6 to 12 months post-OLT; therefore, infections occurring during that time period and afterward generally resemble those of the general population. Screening strategies applied to determine the risk of an infection after transplantation and the use of prophylactic antimicrobial therapy have reduced the incidence of OIs after OLT. This article will review the various causes of infection post-OLT and the therapies used to manage complications. PMID:27134589

  18. Transoesophageal echocardiography during liver transplantation

    PubMed Central

    De Pietri, Lesley; Mocchegiani, Federico; Leuzzi, Chiara; Montalti, Roberto; Vivarelli, Marco; Agnoletti, Vanni

    2015-01-01

    Liver transplantation (LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver transplant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the procedures as a result of both the disease process and the surgery. Transoesophageal echocardiography (TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. Moreover, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure. PMID:26483865

  19. Postreperfusion syndrome during liver transplantation

    PubMed Central

    2015-01-01

    As surgical and graft preservation techniques have improved and immunosuppressive drugs have advanced, liver transplantation (LT) is now considered the gold standard for treating patients with end-stage liver disease worldwide. However, despite the improved survival following LT, severe hemodynamic disturbances during LT remain a serious issue for the anesthesiologist. The greatest hemodynamic disturbance is postreperfusion syndrome (PRS), which occurs at reperfusion of the donated liver after unclamping of the portal vein. PRS is characterized by marked decreases in mean arterial pressure and systemic vascular resistance, and moderate increases in pulmonary arterial pressure and central venous pressure. The underlying pathophysiological mechanisms of PRS are complex. Moreover, risk factors associated with PRS are not fully understood. Rapid and appropriate treatment with vasopressors, volume replacement, or venesection must be provided depending on the cause of the hemodynamic disturbance when hemodynamic instability becomes profound after reperfusion. The negative effects of PRS on postoperative early morbidity and mortality are clear, but the effect of PRS on postoperative long-term mortality remains a matter of debate. PMID:26634075

  20. Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation

    PubMed Central

    Mazza, Giuseppe; Rombouts, Krista; Rennie Hall, Andrew; Urbani, Luca; Vinh Luong, Tu; Al-Akkad, Walid; Longato, Lisa; Brown, David; Maghsoudlou, Panagiotis; Dhillon, Amar P.; Fuller, Barry; Davidson, Brian; Moore, Kevin; Dhar, Dipok; De Coppi, Paolo; Malago, Massimo; Pinzani, Massimo

    2015-01-01

    Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5 × 5 × 5 mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development. PMID:26248878