Hugh B. Fackrell Filename: Hepatite.ppt Viral Hepatitis Hugh B. Fackrell Filename: Hepatite.ppt

Hepatitis Virus Outline Definitions Classification Structure Multiplication Clinical manifestations Epidemiology Diagnosis Control Baron’s Web Site

Hepatitis an ancient disease, the etiology has only recently (50 yrs.) been revealed.

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

Bilirubin Bilirubin: greenish-yellow pigment accumulates in the blood and tissues Jaundice - yellow tinge in the skin and eyes caused by bilirubin

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

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

Hepatitis symptoms Swelling and tenderness of liver Jaundice -yellow tinge in the skin and eyes dark urine transaminase, alkaline phosphatase levels increased

Viral Hepatitis Liver infection caused by several UNRELATED VIRUSES Inflammation and necrosis of the liver 50% of HAV & HBV are subclincal

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”

“Infectious hepatitis” “Epidemic hepatitis” HAV Hepatitis A “Infectious hepatitis” “Epidemic hepatitis” HAV

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

Hepatitis A Structure Picornavirus Only one serotype Enterovirus type 72 27-29 nm icosahedral ssRNA

Hepatitis A Host Defenses antibodies develop late in incubation period IgM within a week of dark urine peaks a week later lasts 40-60 days IgG after IgM peaks 60-80 days lasts many years

Hepatitis A Epidemiology Global distribution- underreported Fecal-oral route, person to person water Overcrowding & poor sanitation Infected food handlers common vector

Annual Incidence Viral food borne diseases Total Viral food borne 30,883,391 Total Microbial food borne incidence 38,629,64 Norwalk-like viruses 23,000,000 Rotavirus 3,900,000 Astrovirus Hepatitis A 83,391 Food-Related Illness and Death in the United Stateshttp://www.cdc.gov/ncidod/eid/vol5no5/mead.htm CDC

Hepatitis A Diagnosis Clinical manifestions Viral antigens Immunoelectron microscopy RIA ELISA Immune Adherence hemagglutination (old method) Viral antibodies

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

Hepatitis B “Serum hepatitis” HBV

Hepatitis B Clinical Manifestations typical viral hepatitis symptoms 4-26 week incubation period more severe than HAV CHRONIC PERSISTENT HEPATITIS CHRONIC ACTIVE HEPATITIS

Hepatitis B Structure Hepadnavirus dsDNA, circular, 3200 nucleotides enveloped icosahedral virus 42 nm

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

3 forms of HBV

Dane Particles

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

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

Hepatitis B Prevalence AREA HBsAg anti HBsAg Western Europe 0.2-0.5% 4-6% USA Eastern Europe 2-7 % 20-55% USSR China 8-20 % 70-95% Asia

Hepatitis B Diagnosis Electron microscopy Viral DNA polymerase Viral DNA probes Serology

Corresponding antibodies to each antigen occur 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

Hepatitis B Control No specific control Passive Immunization HBV immunoglobulin 250-500 IU within 48 hours neonates of infected mothers -immediately after birth Active Immunization HBsAg recombinant DNA in yeast

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

Transformed cells lose contact inhibition continue to divide form random aggregations can become invasive Not warts: Papovavirus

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. 5000 deaths / year

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

Hepatitis C HCV Non -A Non-B

Hepatitis C Clinical Manifestations resembles HBV persistent carrier state 50% of patients have chronic liver damage associated with hepatocellular carcinoma

Hepatitis C is probably caused by several different viruses

Hepatitis C Epidemiology in USA causes 90% of post transfusion hepatitis Mother to infant transmission

Hepatitis C Diagnosis C100-3 recombinant viral antigen anti c100-3 marker of chronic infection

Hepatitis A HAV Hepatitis B HBV Hepatitis C HCV 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 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 D HDV

Hepatitis D 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.

Hepatitis D Clinical Manifestations Dual infection is more severe than HBV fulminating hepatitis severe rapidly progressive hepatitis severe exacerbations

Hepatitis D Structure 35-37 nm virus particle shares coat protein of HBV small RNA genome one serotype

Hepatitis D Epidemiology hemophiliacs and IV drug users Contaminated blood and blood products

Geographic distribution of HDV

Hepatitis D Diagnosis Clinical manifestations Delta antigen Immunofluorescence RIA ELISA Anti delta antigen same as above

Hepatitis E Virus

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.