1 1/24/2019 Viral Hepatitis Hugh B. Fackrell Filename: Hepatite.ppt

2 1/24/2019 Hepatitis Virus Outline  Definitions  Classification  Structure  Multiplication  Clinical manifestations  Epidemiology  Diagnosis  Control Baron’s Web Site Baron’s Web Site

3 1/24/2019 Hepatitis  an ancient disease, the etiology has only recently (50 yrs.) been revealed.

4 1/24/2019 Hepatitis  An inflammatory disease - necrosis of hepatocytes - mononuclear response destroys liver architecture  Liver excretion of bile pigments such as bilirubin into the intestine is interrupted

5 1/24/2019 Bilirubin  Bilirubin: greenish-yellow pigment accumulates in the blood and tissues  Jaundice - - yellow tinge in the skin and eyes - caused by bilirubin

6 1/24/2019 Types of Jaundice  Pre hepatic: Hemolytic Jaundice - normal feces, anemia, reticulocytes  Hepatic: Hepatocellular Jaundice - fecal fat, bilirubinuria, Alkaline phosphatase high, gamma globulins high  Post Hepatic: Obstructive Jaundice - fecal fat, bilirubinuria, alkaline phosphatase high

7 1/24/2019 Jaundice of the Newborn  Premature infants  bilirubin increases from birth  peaks at one week  caused by - 1:excessive hemolysis - 2:immature liver function

8 1/24/2019 Hepatitis symptoms  Swelling and tenderness of liver  Jaundice -yellow tinge in the skin and eyes  dark urine  transaminase, alkaline phosphatase levels increased

9 1/24/2019 Viral Hepatitis  Liver infection caused by several UNRELATED VIRUSES  Inflammation and necrosis of the liver  50% of HAV & HBV are subclincal

10 1/24/2019 Hepatitis types  Hepatitis A - HAV "infectious hepatitis"  Hepatitis B - HBV "serum hepatitis"  Hepatitis C - HCV non A, non B  Hepatitis D - HDV Delta virus  Hepatitis E - HEV similar to type “A”

11 1/24/2019 Hepatitis A “Infectious hepatitis” “Epidemic hepatitis” HAV

12 1/24/2019 Hepatitis A Clinical manifestations  asymptotic or anicteric in children  3-5 week incubation period  liver inflammation  malaise - flu like symptoms  self limiting  low mortality

13 1/24/2019 Hepatitis A Structure  Picornavirus  Only one serotype  Enterovirus type 72  nm icosahedral  ssRNA

14 1/24/2019 Hepatitis A Host Defenses  antibodies develop late in incubation period  IgM - within a week of dark urine - peaks a week later - lasts days  IgG - after IgM - peaks days - lasts many years

15 1/24/2019 Hepatitis A Epidemiology  Global distribution- underreported  Fecal-oral route, - person to person - water  Overcrowding & poor sanitation  Infected food handlers common vector

16 1/24/2019 Annual Incidence Viral food borne diseases  Norwalk-like viruses - 23,000,000  Rotavirus - 3,900,000  Astrovirus - 3,900,000  Hepatitis A - 83,391  Total Viral food borne 30,883,391  Total Microbial food borne incidence - 38,629,64 CDC

17 1/24/2019 Hepatitis A Diagnosis  Clinical manifestions  Viral antigens - Immunoelectron microscopy - RIA - ELISA - Immune Adherence hemagglutination (old method)  Viral antibodies

18 1/24/2019 Hepatitis A Control  No specific control  Improve hygiene and sanitation  Human immunoglobulin - 2 IU anti Hepatitis A /kg body weight  HAV vaccines in clinical field trials

19 1/24/2019 Hepatitis B “Serum hepatitis” HBV

20 1/24/2019 Hepatitis B Clinical Manifestations  typical viral hepatitis symptoms  4-26 week incubation period  more severe than HAV  CHRONIC PERSISTENT HEPATITIS  CHRONIC ACTIVE HEPATITIS

21 1/24/2019 Hepatitis B Structure  Hepadnavirus  dsDNA, circular, 3200 nucleotides  enveloped icosahedral virus  42 nm

22 1/24/2019 Australia antigen “Dane particle”  small pelomorphic particles 20-22nm  tubular forms  excess viral capsids released into blood stream

23 1/24/ forms of HBV

24 1/24/2019 Dane Particles

25 1/24/2019 Hepatitis B Host Defenses  Cell mediated Immunity - important for recover in acute phase - autoimmune liver damage in chronic infections  Humoral Immunity - not always protective - HBsAg for Vaccines  Interferon - not detected during infection - exogenous application effective

26 1/24/2019 Hepatitis B Epidemiology  Parenterally ie via blood, saliva, menstrual and vaginal discharges, semen and breast milk  infected blood and blood products  sexual contact  perinatally from mother to child

27 1/24/2019 Hepatitis B Prevalence AREA HBsAg anti HBsAg AREA HBsAg anti HBsAg Western Europe % 4-6% USA Eastern Europe 2-7 % 20-55% USSR Eastern Europe 2-7 % 20-55% USSR China 8-20 % 70-95% Asia

28 1/24/2019 Hepatitis B Diagnosis  Electron microscopy  Viral DNA polymerase  Viral DNA probes  Serology

29 1/24/2019 Hepatitis B Serology  Hepatitis B surface antigen- HBsAg - 10 subtypes  Hepatitis B core antigen- HBsCAg  Soluble core associated antigen HBeAg Corresponding antibodies to each antigen occur

30 1/24/2019 Hepatitis B Control  No specific control  Passive Immunization - HBV immunoglobulin IU within 48 hours - neonates of infected mothers -immediately after birth  Active Immunization - HBsAg - recombinant DNA in yeast

31 1/24/ Transformation of the cell by virus 2. Helper virus if the transforming virus is defective 3. Co-carcinogen, chemical, cigarette smoke HBV & Cancer

32 1/24/2019 Transformed cells  lose contact inhibition  continue to divide  form random aggregations  can become invasive Not warts: Papovavirus

33 1/24/2019 Primary Hepatocellular Carcinoma  Highest incidence: - Central Africa - Southeast China - Pacific Islands, Borneo, Sarawak, Taiwan  Icteric symptoms: - jaundice, dark urine, pale stools  Global 250,000- 1,000,000 deaths /year  U.S.A deaths / year

34 1/24/2019 Acute Hepatitis B 90%1% Resolution Fulminant Hepatitis 90%1% Resolution Fulminant Hepatitis 50% 50% Resolution Asymptomatic Carrier Chronic Chronic Active Cirrhosis Hepatic Cell Carcinoma Extrahepatic Disease Hepatitis Acute HBV & Cancer

35 1/24/2019 Hepatitis C HCV Non -A Non-B

36 1/24/2019 Hepatitis C Clinical Manifestations  resembles HBV  persistent carrier state  50% of patients have chronic liver damage  associated with hepatocellular carcinoma

37 1/24/2019 Hepatitis C is probably caused by several different viruses

38 1/24/2019 Hepatitis C Epidemiology  in USA causes 90% of post transfusion hepatitis  Mother to infant transmission

39 1/24/2019 Hepatitis C Diagnosis  C100-3 recombinant viral antigen  anti c100-3 marker of chronic infection

40 1/24/2019 Structure Cultured in cells Epidemiology Transmission Incubation period Symptoms Jaundice Onset Vaccine Diagnostic tests RNA yes endemic & epidemic oral/fecal, water & food 2-7 weeks fever, G-I tract disorder 1 case in 10 acute/short not available yes DNA no endemic blood/serum, close contact 1-6 months fever, rash, arthritis common gradual/chronic yes HBV no endemic blood/serum, intimate contact 2-8 weeks similar to HBV common acute/chronic not available yes Hepatitis A HAV Hepatitis B HBV Hepatitis C HCV

41 1/24/2019 Hepatitis D HDV

42 1/24/2019  Dependovirus, it is defective and cannot produce infection unless the cell is also infected with HBV.  Viroid - a naked strand of RNA that enters the cell in piggy-back fashion.

43 1/24/2019 Hepatitis D Clinical Manifestations  Dual infection is more severe than HBV  fulminating hepatitis  severe rapidly progressive hepatitis  severe exacerbations

44 1/24/2019 Hepatitis D Structure  nm virus particle  shares coat protein of HBV  small RNA genome  one serotype

45 1/24/2019 Hepatitis D Epidemiology  hemophiliacs and IV drug users  Contaminated blood and blood products

46 1/24/2019 Geographic distribution of HDV

47 1/24/2019 Hepatitis D Diagnosis  Clinical manifestations  Delta antigen - Immunofluorescence - RIA - ELISA  Anti delta antigen - same as above

48 1/24/2019 Hepatitis E Virus

49 1/24/2019 Hepatitis E  fecal/oral route  predominantly found in developing countries but is world wide.  symptoms similar to HAV but mortality 1- 2% (ten times that of Hepatitis A).  epidemics - India, Pakistan, Nepal, Burma, North Africa and Mexico.