Transcript Hepatitis viruses

Hepatitis viruses
Prof. Dr. Asem Shehabi
Faculty of Medicine
University of Jordan
Hepatitis viruses Classification
 Hepatitis is inflammation of liver cells.. followed first
by accumulation of bilirubin in liver & other body's
tissues.. Jaundice/yellow colored Skin & Eye, Dark
Urine, Pale stools, Fever, Weakness & Myalgia.
 Viral Hepatitis caused directly and mostly by five
viruses : Hepatitis A (HAV), Hepatitis B (HBV) ,
Hepatitis C (HCV), Hepatitis D (HDV), Hepatitis E
(HEV).
 Other viruses that may cause mild to severe form of
Hepatitis as complication : Herpes simplex virus 1+2,
Yellow fever virus, Cytomegalovirus, Epstein-Barr
virus, & certain Enteroviruses.
Hepatitis A Virus
 Part of Picornavirus Group .. A small ss+ve RNA
covered by a Protein shell.. Non-enveloped.. stable
to Acid & Heat.. Survive at 0-25 C.. Few Days-Weeks
in water & fresh food.
 It still highly Endemic in Most Developing Countries..
including All Arab Countries.
 Human Hepatitis virus (HAV) causes often Epidemic
outbreaks ..One main serotype.. 4 genotypes .
 Transmission: Fecal-oral route.. Personal contact,
Families.. Schools, Restaurants.. contamination water,
Shellfish, Fresh vegetables with fecal sources.
 Often associated with Low Standard of Hygiene in
Restaurants .
2/
 Clinical Features: Incubation: 2-6 weeks.
Virus multiplies first intestinal mesenteric
Lymph nodes.. Spread to Blood causing mild
viremia & Liver cells inflammation.. liver
macrophages.. Return back from liver via bile
duct to intestines.. large amount viruses
particles excreted in feces, less in urine.
 HAV causes only acute infection.. mostly mild liver
inflammation / Jaundice in Children (5%).. More
severe Jaundice in adults ..Rarely Liver Cirrhosis/
Lever failure & Death.
 Hepatitis liver damage is due to immune response
/hypersensitivity.. Increase amount Cytotoxic TCells & release of Cytokines..
Hepatitis A-2
 There is no chronic infection cases nor healthy
carriers.. Infected children may excrete virus up
to 6 months.
 Most children recover from infection/Jaundice
within 1- 4 week.. Adults 2-8 weeks.
 Lab diagnosis: Anti-HAV IgM indicates Acute
infection.. IgG indicates Immunity .. Mostly
Long-life immunity after natural infection.
 Inactivated HAV Vaccine is given
intramuscularly 2- doses, Children 0-1-year ..
Protection up to 95%.. AHV+HBV Vaccine is
available..No effective drug treatment.
Hepatitis B-1
 HBV has ds-DNA.. surrounded by capsid & envelop
with complex structure ( Fig.-1) .
 Smallest human virus.. Replication in hepatocell
nucleus.. Free virus DNA can be integrated as
extrachromosomal nucleus. . other part host cells
chromosomes.
 Three major HBV particles:
 HBsAg: Composed 3 surface antigens ( M, S,Lglycoproteins+ lipoprotein) embedded in outer
Lipid envelope.
 HBsAg presence in blood indicates acute HBV
infection .. produced in excess amount as small
spheres and filaments in blood & liver cells..
Hepatitis B Virus
2/
 HBcAg: composed protein core antigen nucleocapsid
attached to viral DNA & DNA polymerase enzyme/
Dane particles are virus infectious part. in host
plasma.. Associated with Acute Clinical
features/chronic liver infection
 HBeAg: is derived from HBcAg during replication..
Present in blood during acute/chronic infection.
 HBV Classified in 8 major genotypes (A-H) &
many subtypes.. According to the nucleotide
sequences of each strain.. Each country has a specific
number of genotype strains.
 HBV is heat-resistance up 20 minutes in boiling water,
UV-Light.. Survive in blood droplets few days.. Killed
by Autoclave/Formalin or 10% of hypochlorite
solutions..24 hrs contact time..Survive few days.
HBV Antigens
2/
 HBV is highly endemic in many countries.. About 300
millions chronic carriers worldwide.. One Million death
occurs yearly worldwide.
 Jordan has about 2% chronic carriers.
 HBV is transmitted horizontally by blood
transfusion.. vertically from infected mother
through maternal fluid/blood to infant during
delivery.. Less by transplacental route , Blood
products, needle stick injures, saliva, semen or
biting / scratching..
 Intravenous drug use & sexual transmission
is major infection source for adults in developed
countries.
HBV Infection-3
 HB Incub. period 2-6 months.. mean 3 months..
causes acute/ chronic hepatitis. Acute hepatitis B
ranges from subclinical disease to fulminate hepatic
failure in 2% of cases /death within few weeks-months
according to the immunological response .
 Acute hepatitis begins with loss of appetite, nausea,
vomiting, fever, abdominal pain, extreme fatigue..
Later few weeks Jaundice. This may indicates start of
recovery or more severe disease.
 About 90% of infected neonates .. 50% of infected
young children will become chronically infected. . only
about 5%-10% of immune competent adults infected
with HBV develop chronic hepatitis B.
4/
 Adult acute infection: About 95% recover without
complications..
 Chronically infected.. especially Neonates/Children..
Their acute infection may not be clinically recognized.
 Immunity: Infection induce both B & T cell responses..
Chronic liver damage occurs with increased immunemediated destruction of hepatocytes due to cytotoxic
T cell reaction & autoimmune reaction.. causing Liver
cirrhosis.
 Chronic hepatitis..with liver disease / serious liver
cirrhosis.. May result later in Fulminant hepatitis or
Hepatocellular carcinoma & death (1%) within 10-40
years.. Especially in association with other infectious
agents..like Malaria, Bilharzias ,AIDS.
Interpretation of serologic Assays of HBV
infection
HBsAg
Anti-HBS
Anti-HBc
Anti-HBe
HBeAg
-ve
No infection
-ve
+ve
-ve
+ve
+ve
Interpretation
Vaccination
+ve
+ve
+ve
Immunity after
recent infection
+ DNA
+ve
Acute /chronic
infection
Laboratory Diagnosis
 The diagnosis of HBV infection is generally made on
the basis of blood serology. Virtually all persons
infected with HBV, either acutely or chronically, will
have HBsAg, HBeAg , Anti-HBc , + HBV DNA
 Elevated transaminases/ alanine aminotransferase &
Serum bilirubin for more than 2 weeks..
 HBsAg is detectable several week after acute
infection with/without the onset of clinical symptoms.
 Presence of HBeAg + HBV DNA indicates acute
infection ..Patient is highly infectious .
 Persons who develop an immune response against
HBV infection show mostly : 1) Anti-HBsAg 2) AntiHBcAg 3) Anti- HBsAg within 6-12 months.
Treatment & Prevention
 Persistent HBeAg & HBV DNA have a generally
worse prognosis .. A greater chance of developing
Liver cirrhosis .. hepatocellular carcinoma.
 Accidental or acute HB infection can be treated with
HB immune-globulin (HBIG) & lamivudine
 HBIG should be given within 24 hs and 48 hs after
accidental infection & Plus HBV Vaccine
 Adults Vaccination – HBV: 2-3 doses..
Intramuscularly.. 95 % protection
 Vaccination newborn babies: 0, 1, 6 months
about100% protection..
 Protection is confirmed by presence high titers of
Anti-ABsAg >100 IU
Hepatitis D
 HDV.. called Delta virus.. is a small circular
RNA.. Its envelop composed of HBsAg
..Following attachment to HBsAg becomes
infectious agent.
 HDV infection only occurs in the presence of
HBV infection.
 First discovered in Italian patients infected with
HBV.. Mostly found in elder patients & chronic
cases.
 HDV infection is transmitted mostly by blood
and blood products. The risk factors for
infection are similar to those for HB infection..
HDV ..Commonly found intravenous drug users.
Hepatitis D-2
 Co-infection (HBV+HDV) is associated more
with liver cirrhosis , chronic disease &
complications.
 Severe acute HB infection could suggest
presence HD co-infection.
 Co-infection in a patient with HB is diagnosed
by the presence of IgM HDV antibodies
 Treatment: Alpha Interferon+ Lamivudine is
used to treat patients with chronic hepatitis B
and hepatitis D infection..
 HBV vaccine prevent infection with HDV.
Hepatitis C
 HCV : Part of Flavi virus group..small enveloped
SS+ RNA covered by 2 envelop proteins (E1, E2), 6
Genotypes & many subtypes..Less Resistance to
heat, dryness & disinfection solutions than HBV.
 HCV infection is more prevalent in developing
countries than developed countries. Types 1
Worldwide , Type 4 Arab countries.. Mostly in Egypt
(15 % population).
 Replication: Hepatocells, Lymphocytes, Stem cells
Bone Marrow
 Incubation period: 6-8 weeks.. Mostly mild acute
hepatitis or asymptomatic without Jaundice, Abnormal
Liver Function tests .. Slowly progressive to Liver
Chronic disease.. Cirrhosis or Hepatocellular
Carcinoma (50%) after many years .
2/
 Transmission: Blood transfusions, blood products,
organ donation , intravenous drug abusers, needlesticks injures , Haemodialysis patients, Rarely
through sexual contact .
 Mother to child transmission occurs during delivery by
maternal fluids, blood .. No vertical transmission.
 Diagnosis: Anti-HCV IgM indicates acute / chronic
infection.
 Anti-HC V IgG alone indicates exposure ..Not
Chronic case
 Combination therapy alpha-interferon & ribavirin
for treatment acute /chronic cases..at least 12 months.
 There is no vaccine available due to continuous
change of HCV envelop antigens.
Hepatitis E
 HEV ss(+)RNA.. It is still not well classified.. Heat and Acid
stable.. Fecal-oral route. Transmission: Oral-fecal route
through Water, Fresh Food, Close contact. Common in India,
Mexico and North Africa..Few cases detected in Jordan
 Pathogenesis:
Similar to HAV replicates in the gut initially, before invading the
liver and return back to blood and Virus DNA shed in the stool
before the onset of major clinical symptom Jaundice.
 Clinical Features: Incubation period 3-8 weeks
Acute, self limiting hepatitis, no chronic carrier state ..most
infections occur in young adults (15-40 )years.
 Complications: Severe cirrhosis in pregnant women &
immunocompromised patients .. Mortality rate is high (up to
40%).
 Diagnosis: Anti-HEV IgG.. Detected only during Acute
disease.. No vaccine or therapy is available.