New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications
Cholestasis is characterised by impaired bile secretion and accumulation of bile salts in the organism. Hereditary cholestasis is a heterogeneous group of rare autosomal recessive liver disorders, which are characterised by intrahepatic cholestasis, pruritus, and jaundice and caused by defects in ge...
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| Language: | English |
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Wiley
2018-01-01
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| Series: | Canadian Journal of Gastroenterology and Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2018/2313675 |
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| author | Eva Sticova Milan Jirsa Joanna Pawłowska |
| author_facet | Eva Sticova Milan Jirsa Joanna Pawłowska |
| author_sort | Eva Sticova |
| collection | DOAJ |
| description | Cholestasis is characterised by impaired bile secretion and accumulation of bile salts in the organism. Hereditary cholestasis is a heterogeneous group of rare autosomal recessive liver disorders, which are characterised by intrahepatic cholestasis, pruritus, and jaundice and caused by defects in genes related to the secretion and transport of bile salts and lipids. Phenotypic manifestation is highly variable, ranging from progressive familial intrahepatic cholestasis (PFIC)—with onset in early infancy and progression to end-stage liver disease—to a milder intermittent mostly nonprogressive form known as benign recurrent intrahepatic cholestasis (BRIC). Cases have been reported of initially benign episodic cholestasis that subsequently transitions to a persistent progressive form of the disease. Therefore, BRIC and PFIC seem to represent two extremes of a continuous spectrum of phenotypes that comprise one disease. Thus far, five representatives of PFIC (named PFIC1-5) caused by pathogenic mutations present in both alleles of ATP8B1, ABCB11, ABCB4, TJP2, and NR1H4 have been described. In addition to familial intrahepatic cholestasis, partial defects in ATP8B1, ABCB11, and ABCB4 predispose patients to drug-induced cholestasis and intrahepatic cholestasis in pregnancy. This review summarises the current knowledge of the clinical manifestations, genetics, and molecular mechanisms of these diseases and briefly outlines the therapeutic options, both conservative and invasive, with an outlook for future personalised therapeutic strategies. |
| format | Article |
| id | doaj-art-685a3a28ce34453096016f8ebfc42ff2 |
| institution | Kabale University |
| issn | 2291-2789 2291-2797 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology and Hepatology |
| spelling | doaj-art-685a3a28ce34453096016f8ebfc42ff22025-02-03T05:45:01ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27892291-27972018-01-01201810.1155/2018/23136752313675New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical ImplicationsEva Sticova0Milan Jirsa1Joanna Pawłowska2Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague 4, 140 21, Czech RepublicLaboratory of Experimental Hepatology, Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Prague 4, 140 21, Czech RepublicDepartment of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute (CMHI), Warsaw 04-730, PolandCholestasis is characterised by impaired bile secretion and accumulation of bile salts in the organism. Hereditary cholestasis is a heterogeneous group of rare autosomal recessive liver disorders, which are characterised by intrahepatic cholestasis, pruritus, and jaundice and caused by defects in genes related to the secretion and transport of bile salts and lipids. Phenotypic manifestation is highly variable, ranging from progressive familial intrahepatic cholestasis (PFIC)—with onset in early infancy and progression to end-stage liver disease—to a milder intermittent mostly nonprogressive form known as benign recurrent intrahepatic cholestasis (BRIC). Cases have been reported of initially benign episodic cholestasis that subsequently transitions to a persistent progressive form of the disease. Therefore, BRIC and PFIC seem to represent two extremes of a continuous spectrum of phenotypes that comprise one disease. Thus far, five representatives of PFIC (named PFIC1-5) caused by pathogenic mutations present in both alleles of ATP8B1, ABCB11, ABCB4, TJP2, and NR1H4 have been described. In addition to familial intrahepatic cholestasis, partial defects in ATP8B1, ABCB11, and ABCB4 predispose patients to drug-induced cholestasis and intrahepatic cholestasis in pregnancy. This review summarises the current knowledge of the clinical manifestations, genetics, and molecular mechanisms of these diseases and briefly outlines the therapeutic options, both conservative and invasive, with an outlook for future personalised therapeutic strategies.http://dx.doi.org/10.1155/2018/2313675 |
| spellingShingle | Eva Sticova Milan Jirsa Joanna Pawłowska New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications Canadian Journal of Gastroenterology and Hepatology |
| title | New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications |
| title_full | New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications |
| title_fullStr | New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications |
| title_full_unstemmed | New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications |
| title_short | New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications |
| title_sort | new insights in genetic cholestasis from molecular mechanisms to clinical implications |
| url | http://dx.doi.org/10.1155/2018/2313675 |
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