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Case Report AK 07.07.2005 Liver biopsy total length 6 mm suggestiv for autoimmune hepatitis Steroid- induced hepatitis Toxic hepatitis. Case Report AK 07.07.2005. Case Report AK female 07.07.2005. Case Report AK female 07.07.2005. Case Report AK female 07.07.2005.
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Case Report AK 07.07.2005 • Liverbiopsy • total length 6 mm • suggestiv for • autoimmune hepatitis • Steroid-inducedhepatitis • Toxichepatitis
Immunohistochemistryfor CD38-positive plasmacellsand CD3-positive and CD8-positive T-cells CD38 forplasmacells CD3 for T-cells Case Report AK female 07.07.2005 CD8 for T-cells
Case Report AK female 07.07.2005 differentiationbetween autoimmune hepatitis and drug-inducedliverdamage on basisofmorphologywithoutclinicaldata not possible
Having knowledgeof total clinicaldata presentedbytheclinician: Morphologicaldiagnosis: Highly suggestive for Drug-inducedliverinjury (DILI) after steroidexposuresomemonthsbeforetherapy Preexisting autoimmune hepatitis not tobeexcluded (a form ofoverlap-syndrom AIH/DILI ?)
Suggestive mechanismsandtargetsoftoxicliverinjury Membrane lesion Transport mechanism (pump) Endoplasmaticreticulum Triggeringof T-cellreactionbymembranetargeting Activationofapoptoticpathwayby TNF-alpha-factor Mitochondrialdamage Modifyied after Lee WM (2003) N ENGL J MED 349,5
Pathogeneticalclassificationofdrug-inducedliverinjury • Intrinsicmechanism • Directinjuryofhepatocytes (dosis-dependent) • Indirectinjuryofhepatocytes (dosis-dependent) • 2. Idiosyncraticmechanism • Immunologicmechanism – allergicreaction, fever, • exanthema, eosinophilia • Metabolicmechanism – mostly via covalentbindingstoproteinsinduce an immunologicalreaction
Drug-inducedliverinjuries • Highly variable changesoflivertisssue • Minimal changes in portaltractsorintralobular • Severechanges in portaltractsorintralobular • Non-alcoholicsteatohepatitis • Autoimmune hepatitis • Acuteandchronicinflammationoftheliver • Cholestasis • Acuteliverfailure • cirrhosis
Drug-inducedliverinjuries • Nospecificpatternofinjuryofthelivertissue • Difficult differential diagnosing • Histologicallygreatresemblanceto viral inducedhepatitis • Occasionaloccurenceofantibodies (e.g. ANA, SMA)
from: Rhen T, Cidlowski JA NEngl JMed (2005) 353, p 1713
possible clinical course and suggestion: primary mild autoimmune hepatitis – followed by corticoid-therapie – followed by severe drug-induced liver injury („overlap-syndrom AIH/DILI”) Hepatitis-E can not be excluded ???