1. Hepatitis & Cirrhosis Dr. Gehan Mohamed Dr. Abdelaty Shawky

2. Learning objectives  Understand the normal Liver Functions so can predict what is the clinical picture when liver failure occur.  Recognize definition of hepatitis and discuss its types(Acute, Chronic, Fulminant).  List different Causes and Patterns of hepatitis.  - Understand the differences between different types of viral hepatitis regarding Transmisson, Carrier state, Chronicity.  List the cellular changes in both Acute and chronic Hepatitis.

3. Learning objectives  Understand difference between chronic hepatitis and fulminant hepatitis.  Discuss definition,etiology of cirrhosis and its variable gross pictures.  discuss the Pathogenesis of Hepatic Encephalopathy.

4. Hepatitis * Definition: Hepatitis is necro-inflammatory liver disease characterized by the presence of inflammatory cells in in the portal tracts then spillover to neighboring parynchmatous liver cells.

5. Normal liver

6. Hepatitis

7. * Causes of hepatitis: 1. Viral: hepatotropic (A, B, C, D….) and non- hepatotropic (cytomegalovirus and Epstein bar virus). 2. Alcoholic. 3. immune mediated: autoimmune hepatitis. 4. Drug induced. 5. Metabolic disorders: Hemochromatosis (due to iron accumulation) and Wilsons disease (copper accumulation) can cause liver inflammation and necrosis.

8. 6. Other causes:  Biliary obstruction by gall stones.  ischemic hepatitis associating shock.  giant cell hepatitis,common in children may be due to viral infection.

9. VirusHep-AHep-BHep-C agentRNADNARNA Transmisson. Feco-oralParenteral -maternal to fetal -sexual -drug abusers - Parenteral -maternal to fetal -Sexual -drug abusers Carrier state None0.1-1.0%0.2-1.0% Chronic Hepatitis None5-10%>50%

10. Patterns of hepatitis  Carrier state: is an individual who harbor and can transmit the virus but has no manifest symptoms.  Acute hepatitis: hepatitis is considered acute if its manifestation persist for period less than six months.  Chronic hepatitis: hepatitis is considered chronic if there is clinical or seriological evidence of liver pathology persistent for more than six consequent months.  Fulminant hepatitis: hepatitis is considered fulminant if massive hepatic cell necrosis happened within few weeks leading to acute hepatic failure and hepatic encephalopathy.

11. Acute Viral Hepatitis

12. Diagnosis of acute hepatitis 1. Clinical picture. 2. Laboratory investigations. 3. Histopathologic diagnosis of liver biopsy.

13. 1. Clinical picture of acute viral hepatitis (AVH):  AVH is more likely to be asymptomatic in younger people.  If AVH is symptomatic, it may be either non specific or specific symptoms.  Initial features are of nonspecific flu-like symptoms include malaise, muscle and joint aches, fever, nausea or vomiting, diarrhea, loss of appetite, and headache.  More specific symptoms and signs are: yellow color of the eyes and skin (i.e., jaundice) and abdominal discomfort from hepatomegaly (swelling of the liver).

14. jaundice

15. 2. Laboratory investigations of AVH: 1. Ultrasound examination to detect any biliary stones, hepatomegaly. 2. Serologic examination to detect : a- Elevated hepatic enzymes as - aspartate aminotransferase(AST) - alanine aminotransferase(ALT). b- Viral hepatitis markers as HBV sAg, HCV Antigen and Antibody c- Autoantibodies as in case of autoimmune hepatitis. d- Polymerase chain reaction(PCR) to identify the virus.

16. 3. Histopathology of AVH:  The normal liver architecture is usually preserved.  Inflammatory cellular infiltrate (plasma cells, lymphocytes and neutrophils) inside portal tracts and around foci of necrosis.  The hepatocytes show:  Apoptosis: the cells appear acidophilic (Councilman bodies).  Hydropic degeneration.  Cholestasis means accumulation of bile in liver cells even canalicular bile plugs can be formed in cases of hepatitis caused by biliary obstruction by stones.  Hepatocyte regeneration.

17. Acute - Hepatitis - Chronic

18. Liver Biopsy – Chronic Hepatitis: the inflammatory cells are present in portal tract and in periportal areas

19. Councilman bodies are eosinophilic dead apoptotic liver cells

20. Cholestasis: accumlation of bile inside hepatocytes

21. Chronic hepatitis

22. * Clinical picture of Chronic hepatitis:  Often no symptoms at all.  It is commonly identified on blood tests performed either for screening or to evaluate nonspecific symptoms.  nonspecific symptoms such as malaise, tiredness and weakness.  The occurrence of jaundice indicates advanced liver damage.  On physical examination there may be enlargement of the liver

23. * Histopathology for chronic hepatitis: I. Portal tracts show: a. Piece meal necrosis: necrosis of the hepatocytes at the limiting plate. b. Portal tract inflammation:  mononuclear inflammatory cells; lymphocytes, macrophages with occasional plasma cells.  Lymphoid follicle formation (with HCV).  Bile duct inflammation (with HCV).

24. II. The hepatic lobules show:  Degeneration: Fatty change (with HCV).  Necrosis:  Focal (spotty) necrosis surrounded by inflammatory cells.  Confluent necrosis and bridging necrosis: with progressive hepatitis.  Dysplasia of hepatocytes (precancerous).  Von Kupffer cell hyperplasia.

25.  Specific diagnostic lesions: Ground glass appearance of hepatocytes (with HBV). Presence of cupper particles inside the hepatocytes (with Wilson disease). Rosseting: occasional arrangement of a group of hepatocytes around a central bile canaliculus. Characteristic of auto-immune hepatitis. III. Fibrosis & Cirrhosis.

26.  Grading of chronic hepatitis by assessing the degree of activity: this is done by examining 4 parameters; portal inflammation, piece meal necrosis, focal (spotty) necrosis and confluent necrosis. The degree of activity is graded as mild, moderate and marked according to the score of these parameters.  Staging of chronic hepatitis by assessment of the degree of fibrosis

27. chronic hepatitis with piece meal necrosis

28. Histopathology show ground glass hepatocytes, which are seen in chronic hepatitis B infections represent accumulations of viral antigen in the endoplasmic reticulum. H&E

29. Histopathology show lymphoid aggregates and fatty change of the hepatocytes, which are characteristically seen in chronic hepatitis C infections

30. Liver cirrhosis

31. * Definition: Chronic Diffuse, irreversible disorder of the liver characterized by; 1.Liver cell degeneration and necrosis. 2.Replaced by extensive fibrosis. 3.Compensatory hyperplasia of the remaining healthy liver cells leading to the formation of the Regenerating parenchymal nodules. 4.Complete loss of normal architecture.

32. * Etiological classification of Cirrhosis: A. Congenital cirrhosis: 1.Congenital syphilis. 2.Hemochromatosis. 3.Glycogen storage disease. 4.Wilson disease. 5.α1 antitrypsin deficiency.

33. B. Acquired cirrhosis: 1. Post-hepatitic (viral). 2. Alcoholic. 3. Biliary cirrhosis. 4. Cirrhosis caused by circulatory disorders e.g. chronic right sided heart failure.

34. * Complications of Cirrhosis: 1. Liver cell Failure 2. Portal hypertension 3. Hepatocellular carcinoma.

35. Normal Liver

36. Micronodular cirrhosis

37. Macronodular Cirrhosis

38. Normal Liver Histology CV PT

39. Liver Biopsy – Cirrhosis

40. Liver Biopsy – Cirrhosis:

41. Liver cell failure

42. * Normal Liver Functions:  Metabolism – Carbohydrate, Fat & Protein.  Secretory – bile, Bile acids, salts.  Excretory – Bilirubin, drugs, toxins.  Synthesis – Albumin, coagulation factors.  Storage – Vitamins, carbohydrates etc.  Detoxification – toxins, ammonia, etc.

43. * Manifestations of liver cell failure 1. Jaundice: yellow colour of skin,mucosa due to hyperbilirubinemia as liver became unable to conjugate bilirubin so it not secreted in urine and so it is reabsorbed by blood and precipitate in tissues. 2. Coagulopathy:→ bleeding tendency 3. Hypoproteinemia specially albumin → decrease osmotic pressure of blood → generalized edema.

44. 4. Hepatic Encephalopathy: caused by the inability of the liver to detoxify amonia which produced by effect of intestinal bacteria on food so this amonia can affect brain causing coma. 5. Hyperestrogenemia due to decrease estrogen degradation by the diseased liver leading to gynaecomastia and testicular atrophy in males

45. Gynaecomastia in cirrhosis i.e. enlargement of male breast due to failure of degradation of estrogen by the diseased liver.

46. Portal hypertension

47.  Portal hypertension leading to; 1. Varices: esophageal varices, piles. 2. Splenomegaly due to splenic congestion. 3. Ascites which is accumulation of transudate in the peritoneal cavity.

48. Ascitis in Cirrhosis

49. Cirrhosis Clinical Features

50. Thanks