How Much Liver Tissue Is Required for Sufficient Histological Staging in Patients with Primary Biliary Cholangitis?

Digestion ◽  
2020 ◽  
pp. 1-9
Author(s):  
Marcel Vetter ◽  
Andreas E. Kremer ◽  
Abbas Agaimy ◽  
Lukas Pfeifer ◽  
Markus F. Neurath ◽  
...  
Keyword(s):  
Liver Tissue ◽  
Primary Biliary Cholangitis ◽  
Histological Staging

scholarly journals TGF-β2 silencing to target biliary-derived liver diseases

Gut ◽  
2020 ◽  
Vol 69 (9) ◽  
pp. 1677-1690 ◽  
Author(s):  
Anne Dropmann ◽  
Steven Dooley ◽  
Bedair Dewidar ◽  
Seddik Hammad ◽  
Tatjana Dediulia ◽  
...  
Keyword(s):  
Liver Disease ◽  
Transforming Growth Factor Beta ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Inflammatory Cells ◽  
Mechanistic Explanation ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease

ObjectiveTGF-β2 (TGF-β, transforming growth factor beta), the less-investigated sibling of TGF-β1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-β2 in biliary-derived liver diseases.DesignAs we also found upregulated TGFB2 in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-β2 in early stage biliary liver disease using the MDR2-KO mice. Specifically, the influence of TgfB2 silencing on the fibrotic and inflammatory niche was analysed on molecular, cellular and tissue levels.ResultsTgfB2-induced expression of fibrotic genes in cholangiocytes and hepatic stellate cellswas detected. TgfB2 expression in MDR2-KO mice was blunted using TgfB2-directed antisense oligonucleotides (AON). Upon AON treatment, reduced collagen deposition, hydroxyproline content and αSMA expression as well as induced PparG expression reflected a significant reduction of fibrogenesis without adverse effects on healthy livers. Expression analyses of fibrotic and inflammatory genes revealed AON-specific regulatory effects on Ccl3, Ccl4, Ccl5, Mki67 and Notch3 expression. Further, AON treatment of MDR2-KO mice increased tissue infiltration by F4/80-positive cells including eosinophils, whereas the number of CD45-positive inflammatory cells decreased. In line, TGFB2 and CD45 expression correlated positively in PSC/PBC patients and localised in similar areas of the diseased liver tissue.ConclusionsTaken together, our data suggest a new mechanistic explanation for amelioration of fibrogenesis by TGF-β2 silencing and provide a direct rationale for TGF-β2-directed drug development.

scholarly journals Organic solute transporter OSTα/β is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury

2018 ◽  
Vol 314 (5) ◽  
pp. G597-G609 ◽  
Author(s):  
Melina M. Malinen ◽  
Izna Ali ◽  
Jacqueline Bezençon ◽  
James J. Beaudoin ◽  
Kim L. R. Brouwer
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Nonalcoholic Steatohepatitis ◽  
Liver Tissue ◽  
Primary Biliary Cholangitis ◽  
Drug Induced ◽  
Organic Solute Transporter ◽  
Organic Solute ◽  
Solute Transporter

The heteromeric steroid transporter organic solute transporter α/β (OSTα/β, SLC51A/B) was discovered over a decade ago, but its physiological significance in the liver remains uncertain. A major challenge has been the lack of suitable models expressing OSTα/β. Based on observations first reported here that hepatic OSTα/β is upregulated in nonalcoholic steatohepatitis, the aim of this research was to develop an in vitro model to evaluate OSTα/β function and interaction with drugs and bile acids. OSTα/β expression in human liver tissue was analyzed by quantitative RT-PCR, Western blotting, and immunofluorescence. Radiolabeled compounds were used to determine OSTα/β-mediated transport in the established in vitro model. The effect of bile acids and drugs, including those associated with cholestatic drug-induced liver injury, on OSTα/β-mediated transport was evaluated. Expression of OSTα/β was elevated in the liver of patients with nonalcoholic steatohepatitis and primary biliary cholangitis, whereas hepatocyte expression of OSTα/β was low in control liver tissue. Studies in the novel cell-based system showed rapid and linear OSTα/β-mediated transport for all tested compounds: dehydroepiandrosterone sulfate, digoxin, estrone sulfate, and taurocholate. The interaction study with 26 compounds revealed novel OSTα/β inhibitors: a biomarker for cholestasis, glycochenodeoxycholic acid; the major metabolite of troglitazone, troglitazone sulfate; and a macrocyclic antibiotic, fidaxomicin. Additionally, some drugs (e.g., digoxin) consistently stimulated taurocholate uptake in OSTα/β-overexpressing cells. Our findings demonstrate that OSTα/β is an important transporter in liver disease and imply a role for this transporter in bile acid-bile acid and drug-bile acid interactions, as well as cholestatic drug-induced liver injury. NEW & NOTEWORTHY The organic solute transporter OSTα/β is highly expressed in hepatocytes of liver tissue obtained from patients with nonalcoholic steatohepatitis and primary biliary cholangitis. OSTα/β substrates exhibit rapid, linear, and concentration-driven transport in an OSTα/β-overexpressing cell line. Drugs associated with hepatotoxicity modulate OSTα/β-mediated taurocholate transport. These data suggest that hepatic OSTα/β plays an essential role in patients with cholestasis and may have important clinical implications for bile acid and drug disposition.

Clinical significance of the Scheuer histological staging system for primary biliary cholangitis in Japanese patients

2017 ◽  
Vol 29 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Tadashi Namisaki ◽  
Kei Moriya ◽  
Mitsuteru Kitade ◽  
Hideto Kawaratani ◽  
Kosuke Takeda ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Staging System ◽  
Japanese Patients ◽  
Primary Biliary Cholangitis ◽  
Histological Staging

scholarly journals Autoimmune liver disease (primary biliary cholangitis/autoimmune hepatitis-overlap) associated with sarcoidosis (clinical cases and literature review)

2019 ◽  
Vol 91 (1) ◽  
pp. 89-94
Author(s):  
E S Burnevich ◽  
E N Popova ◽  
A B Ponomarev ◽  
T P Nekrasova ◽  
M V Lebedeva ◽  
...  
Keyword(s):  
Liver Disease ◽  
Literature Review ◽  
Autoimmune Hepatitis ◽  
Liver Tissue ◽  
Clinical Observation ◽  
Primary Biliary Cholangitis ◽  
Morphological Studies ◽  
Granulomatous Diseases ◽  
Clinical Cases

Clinical features of overlap autoimmune hepatitis/primary biliary cholangitis and morphological-proved sarcoid lesions (lungs, lymph nodes, skin) were performed. Data of long-term clinical observation presented in comparison with the results of laboratory datas, instrumental and morphological studies of liver tissue, lungs, skin. The modern aspects of pathogenesis of association autoimmune and granulomatous diseases arediscussed on the example of clinical cases of combination of cholestatic variants of autoimmune hepatitis and generalized sarcoidosis.

MALDI-imaging: a tool to study lipid distribution in liver tissue during regeneration

2010 ◽  
Vol 48 (01) ◽  
Author(s):  
S Zellmer ◽  
A Veloso ◽  
E Astigarraga ◽  
JA Fernández ◽  
R Gebhardt
Keyword(s):  
Liver Tissue ◽  
Maldi Imaging ◽  
Lipid Distribution

Obeticholic acid for the treatment of primary biliary cholangitis – first data from a real world cohort

2019 ◽  
Author(s):  
R Voitl ◽  
T Hippchen ◽  
C Zhang-Hagenlocher ◽  
KH Weiss ◽  
C Rupp
Keyword(s):  
Real World ◽  
Primary Biliary Cholangitis ◽  
Obeticholic Acid
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