1. Inflammatory Disorders of Liver Inflammatory Disorders of Liver GIT Module, Pathology Rana Bokhary, MD, FRCPC

2. Inflammatory Disorders Of The Liver - Causes Mainly infectious: Mainly infectious: 1. Miliary T.B. 2. Malaria 3. Salmonelloses 4. Candidiasis 5. Amebiasis 6. Viruses Others: Others: 1. Autoimmune 2. Alcohol 3. Drugs / toxins

3. Viral Hepatitis - Etiology Viral Hepatitis - Etiology Hepatotropic Viruses: “most common” Hepatotropic Viruses: “most common” HAV, HBV, HCV, HDV, HEV 5 Hepatitis viruses: HAV, HBV, HCV, HDV, HEV HGV: HGV: non pathogenic Other Viruses: Other Viruses: Herpes viruses “EBV, HSV & CMV” Yellow fever Rubella Adenovirus Enterovirus

4. The Hepatitis Viruses (Table 16-4) Hepatitis E Hepatitis D Hepatitis C Hepatitis B Hepatitis A Virus ssRNACircular defective ssRNA ssRNAPartially dsRNAssRNA Type of virus CalicivirusDeltaviridaeFlavirideaHepadenavirusRelated to picornavirus Viral family Fecal-oralParentralParentral; intranasal cocaine use is a risk factor Parentral, sexual contact, perinatal Fecal-oral (contaminated food or water) Route of transmission 4-5 weeksSame as HBV7-8 weeks1-4 months2-4 weeks Mean incubation period Never5% (coinfection); ≥ 70% for superinfection ~ 80%10%Never Frequency of chronic liver disease PCR for HEV RNA; detection of serum IgM & IgG Abs Detection of IgM & IgG Abs; HDV RNA serum; HDAg in liver PCR for HCV RNA; 3 rd generation ELISA for Ab detection Detection of HBsAg or antibody to HBcAg Detection of serum IgM AbsDiagnosis

5. Potential Outcomes of HBV Infection

6. Potential Outcomes Of HCV Infection

7. Clinical Syndromes & Outcomes of Hepatitis A. Asymptomatic acute infection: A. Asymptomatic acute infection: Serologic evidence only B. Acute Hepatitis: B. Acute Hepatitis: Icteric or anicteric C. Chronic Hepatitis: C. Chronic Hepatitis: With or without progression to cirrhosis D. Chronic carrier state: D. Chronic carrier state: Asymptomatic without apparent disease E. Fulminant Hepatitis: E. Fulminant Hepatitis: Submassive to massive necrosis  acute liver failure HAV, HCV & HEV do not generate a carrier state HAV, HCV & HEV do not generate a carrier state HAV & HEV do not progress to chronic hepatitis HAV & HEV do not progress to chronic hepatitis

8. Acute Viral Hepatitis

10. Ballooning Degeneration

11. Apoptotic Cell

12. Portal Tract Infiltrate with Interface Hepatitis

14. HBV Ground Glass Cell HBsAg Immunostain

15. HCV – Lymphoid Follicles

16. HCV - Steatosis

18. Chronic HCV Hepatitis

19. Cirrhosis Secondary to Viral Hepatitis

20. Cirrhosis

21. Main Morphologic Features of Acute & Chronic Viral Hepatitis Table 16-5 Acute Hepatitis Gross: Enlarged, reddened liver; greenish if cholestatic Parenchymal changes (microscopic) Hepatocyte injury: swelling (ballooning degeneration) Cholestasis: canalicular bile plugs HCV: mild fatty change of hepatocytes Hepatocyte necrosis: isolated cells or clusters Cytolysis(rupture) or apoptosis (shrinkage) If severe: bridging necrosis (portal-portal, central-central, portal-central) Lobular disarray: loss of normal architecture Regenerative changes: hepatocyte proliferation Sinusoidal cell reactive changes Accumulation of phagocytosed cellular debris in Kupffer cells Influx of mononuclear cells into sinusoids Portal tracts Inflammation: predominantly mononuclear Inflammatory spillover into adjacent parenchyma, with hepatocyte necrosis

22. Main Morphologic Features of Acute & Chronic Viral Hepatitis Table 16-5 Chronic Hepatitis Changes shared with acute hepatitis Hepatocyte injury, necrosis, apoptosis, and regeneration Sinusoidal cell reactive changes Portal tracts Inflammation: Confined to portal tracts, or Spillover into adjacent parenchyma, with hepatocyte necrosis “interface hepatitis”, or Bridging inflammation & necrosis Fibrosis: Portal deposition, or Portal & periportal deposition, or Formation of bridging fibrous septa HBV: ground glass hepatocytes (accumulation of HBsAg) HCV: bile duct epithelial cell proliferation, lymphoid aggregate formation Cirrhosis: the End-Stage outcome

23. Liver shrinks in size  wrinkled capsule

24. Massive Hepatic Necrosis Area of collapse

25. Collapsed parenchyma in Hepatitis

26. Liver Abscesses developing Common in developing countries developed Rare in developed countries Causes of each Routes of infection Clinical features Management

27. Autoimmune Hepatitis immunologic abnormalities Syndrome of chronic hepatitis in persons with a heterogenous set of immunologic abnormalities