1. Case Report AK
Liver biopsy
total length 6 mm
suggestiv for
autoimmune hepatitis
Steroid-induced hepatitis
Toxic hepatitis

2. Case Report AK
Low magnification, variable cell infiltration of several partal fields

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

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

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

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

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

8. fibrosis

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

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

11. 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
CD8 for T-cells

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

13. 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 ?)

14. 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

15. 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

16. 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

17. 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)

18. 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

19. 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
???

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

21. Case Report AK female
Collapsed liver regions, Kupffer cells