Abstract：
:The origin and initiating features of PBC remain obscure despite decades of study. However, recent papers have demonstrated loss of canals of Hering (CoH) to be the earliest histologic change in liver biopsy specimens from patients with primary biliary cholangitis (PBC). We posit that CoH loss prior to significant inflammation or evidence of bile duct injury might be a very early, perhaps even an initiating lesion of PBC. As a potential target of inflammatory or toxic injury, CoH loss may initiate rather than follow the cascade of events leading to duct injury and loss and their sequelae. Toxins may be exogenous in origin, such as environmental toxins or drug exposures, or endogenous, resulting from genetic or epigenetic alterations in canalicular bile transporters upstream from the CoH. In turn, this hypothesis suggests that loss of CoH would lead to altered bile flow and composition injurious to downstream bile ducts, because bile composition has not been modulated by normal CoH physiologic functions or because, in the absence of CoH, canalicular fluid flow into the biliary tree is disrupted interfering with soluble trophic factors important for bile duct integrity. Regardless of the pathogenic mechanism causing CoH loss, only following such loss would the characteristic diagnostic findings of PBC become evident: damage to downstream interlobular and sub-lobular bile ducts. To the extent that the causal mechanisms for CoH loss can be identified, clinical identification (as through early identification of CoH loss) and intervention (depending on the inciting cause) may offer promise for treatment of this enigmatic disease.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Theise ND,Crawford JM,Nakanuma Y,Quaglia Adoi
10.1016/j.mehy.2020.109680subject
Has Abstractpub_date
2020-03-16 00:00:00pages
109680eissn
0306-9877issn
1532-2777pii
S0306-9877(20)30146-8journal_volume
140pub_type
杂志文章abstract：:In observing the phenomenon of alterations of tumor cell phenotypes, one may envision a mechanism that induces the change in tumor cell characteristics and the appearance of metastasis. Schirrmacher (1) has suggested that the effect of the microenvironment on tumor cells influences the control of gene expression and t...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(81)90010-4
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journal_title：Medical hypotheses
pub_type： 杂志文章
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journal_title：Medical hypotheses
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.11.022
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journal_title：Medical hypotheses
pub_type： 杂志文章,评审
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journal_title：Medical hypotheses
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journal_title：Medical hypotheses
pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 历史文章,杂志文章
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更新日期：2010-05-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2005.10.011
更新日期：2006-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(92)90057-j
更新日期：1992-12-01 00:00:00
abstract：:This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.07.027
更新日期：2012-08-20 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.02.011
更新日期：2008-08-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2018.07.026
更新日期：2018-10-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1999.1045
更新日期：2000-09-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(97)90223-1
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.11.023
更新日期：2010-05-01 00:00:00
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journal_title：Medical hypotheses
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doi：10.1016/j.mehy.2018.01.014
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(81)90017-7
更新日期：1981-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2012-09-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2020-04-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(03)00235-4
更新日期：2003-11-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2020-10-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(95)90106-x
更新日期：1995-09-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2015.12.003
更新日期：2016-02-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.2001.1511
更新日期：2002-02-01 00:00:00
