Cytolyse hépatique sous dabigatran étexilate chez un sujet âgé

Fulcrand, Julie; Lerooy, Alexandre; Giraud, Jean; Cailliau, Antoine; Delrot, Cédric; Petitpain, Nadine; Auffret, Marine; Pharmacovigilance, le réseau des Centres régionaux de

doi:10.2515/therapie/2013053

Cited by 9 publications

(4 citation statements)

References 6 publications

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“…Increased serum levels of ALT and AST are clinical signs of hepatic injury resulting from loss of hepatocyte membrane integrity, with release of these enzymes into the serum [ 30 ]. Thus, serum levels of ALT and AST activity can be used to indirectly evaluate the integrity of liver tissue after exposure to certain toxic agents [ 31 ]. Therefore, AST appears in higher concentrations in a number of tissues (liver, kidneys, heart, and pancreas) and is released slowly in comparison to ALT.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effects of Aqueous Extract of Opilia celtidifolia (Opiliaceae) Leaves against Ethanol‐Induced Liver Damage in Rats

Amang

Kodji

Mezui

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. Opilia celtidifolia is a plant used in Cameroonian ethnomedicine to cure jaundice. The aim of this study was to evaluate the hepatoprotective activity of O. celtidifolia leaves aqueous extract in rats subjected to ethanol-induced liver damage. Material and Methods. 36 rats including 18 males and 18 females were divided into 6 groups of 3 males and 3 females each, namely, 3 control groups (normal, negative, positive) and 3 test groups. The normal and negative control groups were given distilled water (5 ml/kg), the positive control group received silymarin (100 mg/kg), and the test groups were given O. celtidifolia extract at the doses of 100, 200, and 400 mg/kg. All groups, except the normal control, received concomitantly and daily 40% ethanol (4 g/kg) for 3 weeks to induce hepatotoxicity. Biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, and lipid profile (total cholesterol, HDL, LDL, and triglycerides) were evaluated. Histological sections of the liver, kidneys, and lungs were examined. Qualitative and quantitative phytochemical analysis of the extract were carried out. Results. The groups treated with the extract at the doses of 200 and 400 mg/kg showed a significant decrease ( p < 0.001 ) of transaminases (ALT and AST), ALP, and bilirubin compared with the negative control. These results were confirmed by observation of histological sections of the liver that confirmed protective action of extract against ethanol-induced hepatocellular injury. Conclusion. O. celtidifolia possesses hepatoprotective properties that could be related to its high content of tannins and saponins in the leaves aqueous extract.

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effects of Aqueous Extract of Opilia celtidifolia (Opiliaceae) Leaves against Ethanol‐Induced Liver Damage in Rats

Amang

Kodji

Mezui

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Treatment with dabigatran was stopped, and the patient recovered within the following 2 weeks. The second patient was an 86-year-old lady who was hospitalized with pyelonephritis and acute renal failure [30]. She was treated with dabigatran because of permanent AF.…”

Section: Case Reports and Case Seriesmentioning

confidence: 99%

“…The search was performed on May 23, 2015, and yielded 45 references, which were checked manually for relevance. Seven references [29][30][31][32][33][34][35] were considered to be relevant concerning postmarketing liver injury data.…”

Section: Search Of Databases For Postmarketing Safety Data Of Noacsmentioning

confidence: 99%

Hepatotoxicity of New Oral Anticoagulants (NOACs)

2015

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Case reports and analyses of clinical studies and of pharmacovigilance data suggest that new oral anticoagulants (NOACs) are associated with a small risk for hepatotoxicity. The objective of this publication is to summarize the current data about this subject, with a special emphasis on pharmacovigilance data in the World Health Organization (WHO) Global Individual Case Safety Reports (ICSR) database and on potential mechanisms of hepatotoxicity. For that, all available case reports as well as published analyses of clinical studies were obtained with a detailed search in PubMed. In addition, pharmacovigilance data from VigiBase(®), the WHO Global ICRS database, were extracted and analyzed. The data show that liver injury associated with NOACs was reported in clinical studies and in pharmacovigilance databases. Several case reports described potentially life-threatening hepatotoxicity in patients treated with rivaroxaban or dabigatran. For rivaroxaban, most affected patients were symptomatic and liver injury was most often hepatocellular or mixed. The frequency was between 0.1 and 1 % in clinical studies and was by trend lower than for comparators (mostly enoxaparin or warfarin). Comparing the pharmacovigilance reports for the individual NOACs, more hepatic adverse events were reported for rivaroxaban than for dabigatran or apixaban. With the exception of edoxaban, for which only few reports are available, patients with acute liver failure have been reported for every NOAC, but most patients had concomitant drugs or diseases. So far, there are no clear mechanisms explaining the hepatotoxicity of these drugs. We conclude that hepatotoxicity appears to be associated with all NOACs currently on the market. Hepatotoxicity associated with NOACs is idiosyncratic; it appears at therapeutic doses, is rare and the mechanism is not related to the pharmacological action of these drugs. Prescribers should inform patients about possible symptoms of hepatotoxicity and stop these drugs in patients presenting with severe liver injury.

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“…Blood investigations revealed AST 50 x ULN and ALT x 100 N with modest elevation of serum bilirubin. Dabigatran was stopped and she recovered within few days 12 .…”

Section: Discussion and Literature Revisionmentioning

confidence: 99%