Intrahepatic Cholestasis

Chazouillres, Olivier; Housset, Chantal

doi:10.1002/9780470691861.ch19a

Cited by 6 publications

(4 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An in vitro system that can recreate the complex three-dimensional architecture of the liver and multicellular relationship of the sinusoidal and bile duct systems does not exist at the present time. Moreover, compounds may cause cholestasis through either impairment of bile secretion by the hepatocyte or bile duct injury involving the ductules or the interlobular ducts ( Chazouilleres and Housset, 2007 ). The complex mechanisms of chemical-induced canalicular and chol-angioidestructive cholestasis are nearly impossible to reproduce within the context of our current cell culture devices ( Cullen and Ruebner, 1919 ; Chazouilleres and Housset, 2007 ).…”

Section: The Current State Of Cell-based Hepatic Culture Systemsmentioning

confidence: 99%

Organotypic liver culture models: Meeting current challenges in toxicity testing

LeCluyse

Witek²,

Andersen

et al. 2012

Critical Reviews in Toxicology

305

301

View full text Add to dashboard Cite

Prediction of chemical-induced hepatotoxicity in humans from in vitro data continues to be a significant challenge for the pharmaceutical and chemical industries. Generally, conventional in vitro hepatic model systems (i.e. 2-D static monocultures of primary or immortalized hepatocytes) are limited by their inability to maintain histotypic and phenotypic characteristics over time in culture, including stable expression of clearance and bioactivation pathways, as well as complex adaptive responses to chemical exposure. These systems are less than ideal for longer-term toxicity evaluations and elucidation of key cellular and molecular events involved in primary and secondary adaptation to chemical exposure, or for identification of important mediators of inflammation, proliferation and apoptosis. Progress in implementing a more effective strategy for in vitro-in vivo extrapolation and human risk assessment depends on significant advances in tissue culture technology and increasing their level of biological complexity. This article describes the current and ongoing need for more relevant, organotypic in vitro surrogate systems of human liver and recent efforts to recreate the multicellular architecture and hemodynamic properties of the liver using novel culture platforms. As these systems become more widely used for chemical and drug toxicity testing, there will be a corresponding need to establish standardized testing conditions, endpoint analyses and acceptance criteria. In the future, a balanced approach between sample throughput and biological relevance should provide better in vitro tools that are complementary with animal testing and assist in conducting more predictive human risk assessment.

show abstract

Section: The Current State Of Cell-based Hepatic Culture Systemsmentioning

confidence: 99%

Organotypic liver culture models: Meeting current challenges in toxicity testing

LeCluyse

Witek²,

Andersen

et al. 2012

Critical Reviews in Toxicology

305

301

View full text Add to dashboard Cite

show abstract

“…Clinical and biochemical presentation is characterized by fatigue, pruritus, jaundice and increasing in serum transaminase, ALP, GGT, and hyperbilirubinemia at more advanced stages. The acute onset of cholestatic hepatitis may be observed in viral infection, drug-alcohol toxicity, sepsis-endotoxemia, acquired and hereditary cholestatic disorders, immune-mediated diseases, vascular disorders, and benign or malignant infiltrating disorders such as lymphomas [8]. Liver biopsy is an important diagnostic tool in the cholestasis of unknown origin, especially when a disorder is suspected without direct involvement of the bile ducts, such as cirrhosis, hepatic granulomas, nodular regenerative hyperplasia, sinusoidal dilatation, and storage or infiltrative liver diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Liver biopsy is an important diagnostic tool in the cholestasis of unknown origin, especially when a disorder is suspected without direct involvement of the bile ducts, such as cirrhosis, hepatic granulomas, nodular regenerative hyperplasia, sinusoidal dilatation, and storage or infiltrative liver diseases. HSTCL is a primary non-Hodgkin lymphoma of the liver that is an unusual cause of intrahepatic cholestasis by a mixed pathological mechanism [8]. It is a rare entity, usually manifesting with constitutional "B symptoms", and with signs of liver and spleen involvement such as cytopenias, liver enzyme alteration, or progressive jaundice.…”

Section: Discussionmentioning

confidence: 99%

Hepatosplenic T-Cell Lymphoma Mimicking Acute Onset of Cholestatic Hepatitis in a Young Immunocompetent Man: A Case Report

Metelli

Solimando

Alemanni

et al. 2022

Gastroenterology Insights

View full text Add to dashboard Cite

We herein report a case of hepatosplenic T-cell lymphoma (HSTCL) incidentally found in a 30-year-old man who came to the emergency department after an ankle trauma. At admission, laboratory tests revealed abnormal liver enzymes and pancytopenia, and imaging showed mild hepatosplenomegaly. During hospitalization, the patient’s clinical condition worsened rapidly, with a concomitant increase in cholestatic enzymes, severe jaundice, and the worsening of pancytopenia. Causes of liver injury, including many infectious diseases, were explored until the diagnosis of HSTCL was made by liver and bone marrow biopsies. Subsequently, the patient underwent six cycles of chemotherapy with a CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone or prednisolone) regimen and one with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) but, despite this aggressive treatment, died due to disease progression 2 months after diagnosis. This rare disease should be considered in the diagnostic workup of acute cholestatic hepatitis presenting with concomitant hepatosplenomegaly and cytopenia.

show abstract

“…Cholestasis is an impairment of bile formation either or both flow which may be classified into extrahepatic or intrahepatic cholestasis [1]. Diagnosis of extrahepatic cholestasis is based on laboratory evidence by elevated alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), or conjugated bilirubin with the presence of biliary dilatation in imaging [2].…”

Section: Introductionmentioning

confidence: 99%

Increased liver stiffness by transient elastography and acoustic radiation force impulse imaging in patients with extrahepatic cholestasis

Darweesh

Atef²,

Ramzy³

et al. 2020

European Journal of Gastroenterology &Amp; Hepatology

View full text Add to dashboard Cite

Background Transient elastography and acoustic radiation force impulse (ARFI) imaging are noninvasive tools for liver stiffness measurement (LSM), which may be influenced by cholestasis. Aim The aim of the study was to evaluate the performance of transient elastography and ARFI in extrahepatic cholestasis and correlate changes in LSM with biochemical activity. Materials and methods A total of 38 patients with extrahepatic cholestasis prospectively underwent transient elastography and ARFI. Changes in LSM by transient elastography/ARFI were evaluated after 1 week of ERCP and correlated with biochemical parameters. The optimal ARFI cutoffs according to stages of clinical interest were analyzed. Results Biliary obstruction was calcular in 21 (55.3%) and noncalcular in 17 (44.7%) (benign n = 15, malignant n = 2). After 1 week, adequate biliary drainage reduced total bilirubin from 7.7 to 2.2 mg/dL (P < 0.001) which significantly correlated with reduction of LSM by transient elastography from 12.38 ± 6.68 kPa to 8.08 ± 3.21 kPa (P < 0.001), and by ARFI from 1.73 ± 0.51 m/s to 1.56 ± 0.70 m/s (P = 0.014). The LSM percentage change showed a decrease (nonsignificant, P = 0.843) by 25.83% using transient elastography and a significant decrease (P < 0.001) by 18.42% using ARFI in the improved patients. At initial visit, transient elastography positively correlated with ARFI, bilirubin and platelets, also, transient elastography had a positive correlation with ARFI, bilirubin, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) in follow-up visit. LSM by ARFI (visit 1) negatively correlated with ALT, while in (visit 2), ARFI positively correlated with bilirubin, ALP, GGT and negatively correlated with albumin. Conclusion The increased LSM in patients with extrahepatic cholestasis is reduced after adequate biliary drainage, implying that increased values are not solely due to liver fibrosis, but due to biliary congestion leading temporarily to increased elasticity.

show abstract

Intrahepatic Cholestasis

Cited by 6 publications

References 124 publications

Organotypic liver culture models: Meeting current challenges in toxicity testing

Organotypic liver culture models: Meeting current challenges in toxicity testing

Hepatosplenic T-Cell Lymphoma Mimicking Acute Onset of Cholestatic Hepatitis in a Young Immunocompetent Man: A Case Report

Increased liver stiffness by transient elastography and acoustic radiation force impulse imaging in patients with extrahepatic cholestasis

Contact Info

Product

Resources

About