Hepatitis Viruses Dr. Alvaro Barboza Quintana. Profesor de Patología. Fac. Medicina UANL. Escuela de Medicina ITESM .

1. Hepatitis VirusesDr. Alvaro Barboza Quintana.Profesor de Patología.Fac. Medicina UANL.Escuela de Medicina ITESM.

2. Hepatitis can be caused by some viruses, bacteria, parasites, fungi and chemicals as part of the clinical features that characterizes each disease. But the hepatitis viruses, a heterogeneous group of viruses with an special affinity for the liver, are the mayor cause of viral hepatitis. Liver is often affected by: Citomegalovirus. Mononucleosis. Yellow fever. Virus with high affinity for liver: Hepatitis virus A. Hepatitis virus B. Hepatitis virus C. Hepatitis virus D. Hepatitis virus E. Hepatitis virus F. Hepatitis virus G. Causes of hepatitis

4. agent transmission incubation chronic period hepatitis HAV icosahe- fecal-oral 2-6 wk none dral capsid, RNA HBV enveloped parenteral; 4-26 wk 5-10% of acute DNA close contact HCV enveloped parenteral; 2-26 wk >50% RNA close contact HDV enveloped parenteral; 4-7 wk <5% coinfection, RN close contact 80%superinfect. HEV unenve- water-borne 2-8 wk none loped RNA HGV RNA virus parenteral unknown none

5. Hepatitis A (HAV) A benign, self-limited disease, known as infectious hepatitis. Accounts for about 25% of clinically evident acute hepatitis.

6. Epidemiology Transmission Fecal-oral route. Excreted in the stool of patients 2-3 weeks before, and 8-10 days after, the onset of jaundice. The virus particle is resistant to degradation, remaining infectious in the environment for weeks. • ·Person-to-person transmission.- cause outbreaks in places like institutions. • ·Fecal contamination of a single source.- can lead to sudden epidemies. 

7. Hepatitis A virus Distribution and incidence. Worldwide infection, especially in areas with substandar hygiene and sanitation.

8. Clinical disease HAV causes an acute, highly contagious form of hepatitis:

9. Clinical infection · The pre-icteric stage is characterized by nonspecific,flu-like symptoms of anorexia, nausea, vomiting, and malaise. ·The icteric stage is characterized by hyperbilirubinemia, jaundice, hepatomegaly, right upper quadrant tenderness, and raised serum levels of liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

10. Morfologic changes in acute viral hepatitis are shared among hepatotropic virus inflammatory infiltrate, bile duct reaction, balloning degeneration (were the hepatocite cytoplasm looks empty), macrophage aggregates, cholestasis and apoptosis. Morphologic features in acute hepatitis:

11. Portal tract inflammation, Kupffer's cell hypertrophy and spotty acidophilic necrosis of hepatocytes.

12. Diagnosis • Clinical data • Serologic tests that detect antibodies to HAV. The finding of IgM anti-HAV antibodies indicates current or recent infection, while the finding of IgG anti-HAV antibodies (without IgM antibodies) indicates past exposure to the virus.

13. Treatment Supportive therapy. Immunity after HAV infection is usually lifelong, infrequently waning in the elderly. Relapses occur, but chronic carriers of HAV have not been detected. In developing countries, with inadequate sanitation, infection occurs more in childhood. Prevention with killed virus vaccine.

14. Hepatitis B virus (HBV)

15. Epidemiology • 300,000 people are afected (USA) • Endemic in Italy, Grece, Africa and the southeast of Asia • The hepatocellular carcinoma is endemic in those countries • Asymptomatic patients may have the virus in blood and other body fluids this is why it’s easily transmited • Incubation period: 6 weeks-6 months

16. Transmission • Blood • Sexual contact • Perinatal Risk group • Drug users that share needles • Sexually active people (especially those who are promiscuous) • Patients that have dialysis • Infants born to infected mothers • Healthcare workers

17. Clinical manifestations Acute • Subclinical infections • Are more common than clinical infections • Liver enzymes are elevated • The severity of the disease is related to the viral dose • Jaundice • Fatigue • Abdominal pain • Anorexia • Nausea • Vomiting

18. Clinical manifestations Chronic • Carriers: individuals who have detectable HBsAg (hepatitis B superficial antigen) for at least 6 months • Of patients that become chronic carriers, the majority (90%) develop chronic persistent hepatitis and rest will develop chronic active hepatitis

19. Serologic markers for hepatitis B

20. Serologic markers in chronic HBV

21. Persistent hepatitis B • They remain clinically well, but they are able to infect other people • The liver enzymes may be slightly elevated • It can lead to terminal liver failure

22. Chronic active hepatitis • Patients are more likely to be symptomatic and to have a more severe manifestations Complications of chronic hepatitis • It’s associated with cirrohosis and hepatocellular carcinoma

23. Liver architecture is usually well preserved With lymphoid aggregates in portal tract. Limitant plate damage or interface necrosis.

24. Cirrhosis • Chronic carriers especially those with chronic active hepatitis, may develop cirrhosis

25. HBV as oncogenic factor • Causes between 250,000-1,000,000 deaths worldwide in a year • Approximately 80% of the cases of HC are owed to HBV • The period between the infection with HB until the development of HC could be from 9-35 years

26. Hepatocellular carcinoma. Such liver cancers arise of cirrhosis

27. Hepatocellular carcinoma. There is no discernable normal lobular architecture, though vascular structures are present

29. Prevention • Hepatitis B vaccine (available since 1982) • Routine vaccination of 0-18 year olds • Screening pregnant women and treatment of infants born to infected women • Screening of blood/organ/tissue donors

30. Hepatitis C • 90% of the cases are associated to transfusions Transmission • Blood • Needles • Sexual intercourse

31. Hepatitis C virus

33. Epidemiology • 5-10% of the cases are post-transfusions • It produces cronic hepatitis • Cirrosis  in 20% of the cases • Hepatocellular carcinoma  in 50% of the cases

34. Clinical manifestations • It has 2 types: • Acute: • It could last 4/6 months • Similar to manifestations seen in hepatitis A or B, but with less inflamation • Chronic: • More then 10 years • Leads frecuently to hepatocelluar carcinoma and cirrosis

36. Hepatitis C.

37. Diagnosis and treatment • ELISA • Interferon alfa

38. Hepatitis D virus. Delta agent. • HDV is a defective RNA virus. Needs to be encapsulated by HBsAg. • Superinfection of a chronic carrier of HBV • Progression to cirrhosis in 80%

39. Hepatitis E virus. High mortality range among pregnant women 20%

40. Drug and toxin Induced liver Diseasehepatotoxicity from chemicals

41. Drug Induced liver Disease • Liver is the mayor detoxifying organ in the body. • Liver is subjet to potential damage from pharamceutical and environmental chemicals. • Injury may result from: • Direct toxicity • Hepatic conversion of chemical. • Immune mechanisms.

42. Drug Induced liver Disease • Liver damage from chemicals may be immediate or take months. • Forms of liver injury: • Hepatocyte necrosis • Cholestasis • Insidious onset of dysfunction. • Drug induced chronic hepatitis is indistinguishable from chrinc viral hepatitis

43. Drug Induced liver Disease

44. Drug Induced liver Disease • Reye syndrome • Mitochonrdial dysfuntion in liver and some other organs. • Predminantly in children given acetylsalicylic acid cause of fever. • Produces microvesicular steatosis with severe liver dysfuntion.

45. Alcholic liver disease(Ethanol Metabolism)

46. Epidemiology • It develop only after a "threshold" dose • 600 kg for men and 150 to 300 kg for women. • one must consume eight 12-oz beers, 1 L of wine, daily for a period of 20 years • Almost all people who exceed this threshold dose of ethanol exhibit some biochemical or histologic abnormality suggestive of liver injury

47. Epidemiology • fewer than 50% of people who ingest the calculated threshold dose of ethanol eventually develop serious alcoholic liver disease (e.g., alcoholic hepatitis or fibrosis). • This suggest that the pathogenesis involves hereditary and enviromental disorders.

48. Metabolism • Liver. 3 enzyme systems: ADH, MEOS and catalase. • There exist several isoforms of the ADH enzyme (alfa, beta and gamma) and variation in this changes the metabolic rate of ethanol. Asians (beta2) 20% faster. • ADH acts alone when tissue levels do not exceed 10 mmol/L

49. MEOS • Cytochrome P-450 2E1 (CYP2E1) • also the metabolism of other drugs such as acetaminophen, haloalkanes, and nitrosamines • Chronic ethanol consumption up-regulates CYP2E1 • CYP2E1-mediated ethanol oxidation yields reactive oxygen intermediates • These are capable of provoking hepatocellular damage