Drug-Induced Cholestasis

Bjõrnsson, Einar; Jonasson, Jón G.

doi:10.1016/j.cld.2012.11.002

Cited by 59 publications

(61 citation statements)

References 120 publications

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“…Unlike extrahepatic mechanical bile duct obstruction, which has a clearly defined pathology and good experimental models, the diverse heterogeneous conditions grouped under intrahepatic cholestasis are rather poorly understood and characterized. Intrahepatic cholestasis has multiple etiologies, including liver infections (viral, bacterial, and fungal), sepsis, autoimmune diseases, sarcoidosis, amyloidosis, lymphoma, heart failure,132 and drug reactions (eg, antibiotics, anti-inflammatories, and oral contraceptives) 133. The elevation of CB may result from obstructed bile flow, altered bile ductular integrity, or reduced production of bile due to defective activity of the bile efflux transporters (eg, BSEP, MRPs [Figure 7]).…”

Section: Cholestasis and Bile Duct Obstructionmentioning

confidence: 99%

Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

Levitt¹,

Levitt²

2014

CEG

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Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB) and unconjugated bilirubin (UB). While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis), and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert’s, Dubin–Johnson, Crigler–Najjar, Rotor syndromes). Novel aspects of this review include: 1) quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2) detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3) discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4) pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5) role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6) insights concerning the clinical interpretation of bilirubin measurements.

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Section: Cholestasis and Bile Duct Obstructionmentioning

confidence: 99%

Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

Levitt¹,

Levitt²

2014

CEG

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“…32 Histologically, a cholestatic pattern of liver injury can be classified into acute and chronic injury, of which acute cholestasis is much more common. 33,34 Cholestasis caused by drugs commonly resolves without significant consequences after termination of drug intake. In some instances, liver injury becomes chronic, causing sclerosis and loss of bile ducts, periportal cholate stasis, portal fibrosis, and copper accumulation, which may mimic PSC or PBC.…”

Section: Drug-induced Liver Injurymentioning

confidence: 99%

“…Drugs known to cause LIBD include neuroleptic agents (chlorpromazine, imipramine, carbamazepine, amitriptyline, haloperidol, cyproheptadine, and phenytoin), antibiotics (amoxicillin, flucloxacillin, quinolones, clindamycin, macrolides, and tetracyclines), complementary and alternative medicines (ajmaline and glycyrrhizin), nonsteroidal antiinflammatory drugs (diclofenac and ibuprofen), amiodarone, cimetidine, thiabendazole, and zonisamide, among others. 33,34 Of the whole list, chlorpromazine, ajmaline, and flucloxacillin are the commonly reported drugs associated with LIBD. 35 Primary sclerosing cholangitis-like injury is a relatively uncommon pattern that is mainly seen with infusion of chemotherapy agents into the hepatic artery such as floxuridine and fluorouracil to treat metastatic colorectal cancer to the liver, as well as hepatic arterial chemoembolization in hepatocellular carcinoma.…”

Section: Drug-induced Liver Injurymentioning

confidence: 99%

“…62 The acute intrahepatic cholestasis induced by drugs can be classified into pure (bland) cholestasis and cholestatic hepatitis. 33,34 In pure cholestasis, bile plugs are seen in canaliculi and/or hepatocytes. No inflammation, hepatocyte necrosis, or bile duct damage is identified.…”

Section: Drug-induced Liver Injurymentioning

confidence: 99%

“…Various drugs have been associated with cholestatic hepatitis (eg, erythromycin and chlorpromazine). 33 …”

Section: Drug-induced Liver Injurymentioning

confidence: 99%

See 2 more Smart Citations

Pathophysiology and Diseases of the Proximal Pathways of the Biliary System

Nakanishi¹,

Saxena

2015

Archives of Pathology &Amp; Laboratory Medicine

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Care of the patient with cholestasis hinges on identifying the etiology. Diagnostic steps in cholestatic conditions comprise a thorough patient history, abdominal imaging, distinct serological studies, and liver biopsy. Primary biliary cirrhosis is characterized by distinctive serological and histological findings. The small-duct variant of primary sclerosing cholangitis is very rare and difficult to diagnose; imaging of the bile ducts is not helpful. Graft-versus-host disease is characterized by damage and loss of intrahepatic bile ducts. Drugs can cause injury variably at the level of bile canaliculus or the interlobular bile duct. Loss of bile ducts may be seen with primary biliary cirrhosis, primary sclerosing cholangitis, graft-versus-host disease, and drug-induced liver injury. Progressive familial intrahepatic cholestasis and progressive familial intrahepatic cholestasis represent 2 extreme ends of the spectrum of abnormalities in transporters responsible for bile formation. Intrahepatic cholestasis of pregnancy has a variable incidence in different parts of the world and may be due to abnormalities in transporter molecules.

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HepaRG Cells as a Model for Hepatotoxicity Studies

Guguen‐Guillouzo

2018

Stem Cells in Birth Defects Research and Developmental Toxicology

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Drug-Induced Cholestasis

Cited by 59 publications

References 120 publications

Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

Pathophysiology and Diseases of the Proximal Pathways of the Biliary System

HepaRG Cells as a Model for Hepatotoxicity Studies

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