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Familial intrahepatic cholestasis: New and wide perspectives.

Abstract

BACKGROUND

Progressive familial intrahepatic cholestasis (PFIC) includes autosomal recessive cholestatic rare diseases of childhood.

AIMS

To update the panel of single genes mutations involved in familial cholestasis.

METHODS

PubMed search for "familial intrahepatic cholestasis" alone as well as in combination with other key words was performed considering primarily original studies and meta-analyses.

RESULTS

PFIC1 involves ATP8B1 gene encoding for aminophospholipid flippase FIC1. PFIC2 includes ABCB11 gene, encoding for protein functioning as bile salt export pump. PFIC3 is due to mutations of ABCB4 gene responsible for the synthesis of class III multidrug resistance P-glycoprotein flippase. PFIC4 and PFIC5 involve tight junction protein-2 gene and NR1H4 gene encoding for farnesoid X receptor. Benign Intrahepatic Cholestasis, Intrahepatic Cholestasis of Pregnancy and Low-phospholipid-associated cholelithiasis involve the same genes and are characterized by intermittent attacks of cholestasis, no progression to cirrhosis, reversible pregnancy-specific cholestasis and cholelithiasis in young people. Blood and liver tissue levels of bile-excreted drugs can be influenced by the presence of mutations in PFIC genes, causing drug-induced cholestasis. Mutations in PFIC genes might increase the risk of liver cancer.

CONCLUSION

There is a high proportion of unexplained cholestasis potentially caused by specific genetic pathophysiologic pathways. The use of next generation sequencing and whole-exome sequencing could improve the diagnostic process in this setting.

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  • Authors+Show Affiliations

    ,

    ITEC Unit, Department of Medical and Surgical Sciences, University of Bologna, Italy; Research Centre for the Study of Hepatitis, University of Bologna, Italy; End-stage Liver Disease Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Italy.

    ,

    ITEC Unit, Department of Medical and Surgical Sciences, University of Bologna, Italy; Research Centre for the Study of Hepatitis, University of Bologna, Italy.

    ,

    ITEC Unit, Department of Medical and Surgical Sciences, University of Bologna, Italy; Research Centre for the Study of Hepatitis, University of Bologna, Italy.

    ,

    Bioquant Institute, Heidelberg University, Germany; Heidelberg University Biochemistry Center (BZH), Germany.

    ITEC Unit, Department of Medical and Surgical Sciences, University of Bologna, Italy; Research Centre for the Study of Hepatitis, University of Bologna, Italy. Electronic address: pietro.andreone@unibo.it.

    Source

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    31105019

    Citation

    Vitale, Giovanni, et al. "Familial Intrahepatic Cholestasis: New and Wide Perspectives." Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2019.
    Vitale G, Gitto S, Vukotic R, et al. Familial intrahepatic cholestasis: New and wide perspectives. Dig Liver Dis. 2019.
    Vitale, G., Gitto, S., Vukotic, R., Raimondi, F., & Andreone, P. (2019). Familial intrahepatic cholestasis: New and wide perspectives. Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, doi:10.1016/j.dld.2019.04.013.
    Vitale G, et al. Familial Intrahepatic Cholestasis: New and Wide Perspectives. Dig Liver Dis. 2019 May 16; PubMed PMID: 31105019.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Familial intrahepatic cholestasis: New and wide perspectives. AU - Vitale,Giovanni, AU - Gitto,Stefano, AU - Vukotic,Ranka, AU - Raimondi,Francesco, AU - Andreone,Pietro, Y1 - 2019/05/16/ PY - 2019/01/25/received PY - 2019/04/01/revised PY - 2019/04/12/accepted PY - 2019/5/21/entrez KW - Bioinformatics analysis KW - Cryptogenic disease KW - Genetic variants KW - Pathogenic mutations JF - Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver JO - Dig Liver Dis N2 - BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) includes autosomal recessive cholestatic rare diseases of childhood. AIMS: To update the panel of single genes mutations involved in familial cholestasis. METHODS: PubMed search for "familial intrahepatic cholestasis" alone as well as in combination with other key words was performed considering primarily original studies and meta-analyses. RESULTS: PFIC1 involves ATP8B1 gene encoding for aminophospholipid flippase FIC1. PFIC2 includes ABCB11 gene, encoding for protein functioning as bile salt export pump. PFIC3 is due to mutations of ABCB4 gene responsible for the synthesis of class III multidrug resistance P-glycoprotein flippase. PFIC4 and PFIC5 involve tight junction protein-2 gene and NR1H4 gene encoding for farnesoid X receptor. Benign Intrahepatic Cholestasis, Intrahepatic Cholestasis of Pregnancy and Low-phospholipid-associated cholelithiasis involve the same genes and are characterized by intermittent attacks of cholestasis, no progression to cirrhosis, reversible pregnancy-specific cholestasis and cholelithiasis in young people. Blood and liver tissue levels of bile-excreted drugs can be influenced by the presence of mutations in PFIC genes, causing drug-induced cholestasis. Mutations in PFIC genes might increase the risk of liver cancer. CONCLUSION: There is a high proportion of unexplained cholestasis potentially caused by specific genetic pathophysiologic pathways. The use of next generation sequencing and whole-exome sequencing could improve the diagnostic process in this setting. SN - 1878-3562 UR - https://www.unboundmedicine.com/medline/citation/31105019/Familial_intrahepatic_cholestasis:_New_and_wide_perspectives L2 - https://linkinghub.elsevier.com/retrieve/pii/S1590-8658(19)30553-5 DB - PRIME DP - Unbound Medicine ER -