Case Report AK Liver biopsy total length 6 mm suggestiv for

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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 Low magnification, variable cell infiltration of several partal fields

Case Report AK female 07.07.2005 Portal tract partially involved in the inflammatory process and infiltrated by monuclear inflammatory cells

Case Report AK female 07.07.2005 Mild interface hepatitis, small collaps field , brightening of the adjacent liver tissue

Case Report AK female 07.07.2005 Hydropic swelling, single cell necrosis, beginning rosetting, Kupffercell activation

Case Report AK female 07.07.2005 Dense infiltration by mononuclear inflammatory cells like lymphocytes, plasma cells, eosinophilic polymorph-nuclear granulocytes

Case Report AK female 07.07.2005 Eosinophilic polymorph-nuclear granulocytes and plasma cells

fibrosis

Case Report AK female 07.07.2005 Slight fibrosis, interface hepatitis or piecemeal-necrosis, single cell necrosis, apoptosis, severe intralobular inflammatory activity

Case Report AK female 07.07.2005 Areals with signs of elevated gluconeogenesis (PAS)

Immunohistochemistry for CD38-positive plasma cells and CD3-positive and CD8-positive T-cells CD38 for plasma cells CD3 for T-cells Case Report AK female 07.07.2005 CD8 for T-cells

differentiation between autoimmune hepatitis and Case Report AK female 07.07.2005 differentiation between autoimmune hepatitis and drug-induced liver damage on basis of morphology without clinical data not possible

Having knowledge of total clinical data presented by the clinician: Morphological diagnosis: Highly suggestive for Drug-induced liver injury (DILI) after steroid exposure some months before therapy Preexisting autoimmune hepatitis not to be excluded (a form of overlap-syndrom AIH/DILI ?)

Suggestive mechanisms and targets of toxic liver injury Membrane lesion Transport mechanism (pump) Endoplasmatic reticulum Triggering of T-cell reaction by membrane targeting Activation of apoptotic pathway by TNF-alpha-factor Mitochondrial damage Modifyied after Lee WM (2003) N ENGL J MED 349,5

Pathogenetical classification of drug-induced liver injury Intrinsic mechanism Direct injury of hepatocytes (dosis-dependent) Indirect injury of hepatocytes (dosis-dependent) 2. Idiosyncratic mechanism Immunologic mechanism – allergic reaction, fever, exanthema, eosinophilia Metabolic mechanism – mostly via covalent bindings to proteins induce an immunological reaction

Drug-induced liver injuries Highly variable changes of liver tisssue Minimal changes in portal tracts or intralobular Severe changes in portal tracts or intralobular Non-alcoholic steatohepatitis Autoimmune hepatitis Acute and chronic inflammation of the liver Cholestasis Acute liver failure cirrhosis

Drug-induced liver injuries No specific pattern of injury of the liver tissue Difficult differential diagnosing Histologically great resemblance to viral induced hepatitis Occasional occurence of antibodies (e.g. ANA, SMA)

from: Lee MW, N Engl J Med (2003) 349,5, p 477 (Drug-Induced Hepatotoxicity) Rhen T, Cidlowski JA N Engl J Med (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 ???

Case Report AK female 07.07.2005 Inflammatory activity in the periportal and in the sinusoidal unit

Case Report AK female 07.07.2005 Collapsed liver regions, Kupffer cells