4. Hepatitis A
- Known as infectious hepatitis, Spread
by fecal-oral route, results from the
consumption of contaminated water,
shellfish, or other food.
- It is a picornavirus, 27-nm, naked,
icosahedral capsid, A positive-sense
single-stranded RNA, One serotype.
5. Hepatitis A: Replication:
- Like other picornaviruses, but HAV is not cytolytic and is released by exocytosis.
- Clinical isolates are difficult to grow in cell culture.
6. Hepatitis A: Pathogenesis:
- HAV is shed in large quantity into the
stool approximately 10 days before
symptoms of jaundice appear or
antibody can be detected.
- Although interferon limits viral replication, natural
killer and cytotoxic T cells are required to eliminate
infected cells.
- Antibody, complement, and antibody-dependent
cellular cytotoxicity also facilitate clearance of the
virus and induction of immunopathology.
7. - Icterus resulting from the damage of
the liver occurs when cell-mediated
immune response and antibody to the
virus can be detected.
- Antibody protection against reinfection
is lifelong.
- Unlike HBV, HAV is not associated with
hepatic cancer.
8. Hepatitis A: Epidemiology:
- Spread rapidly because most infected people
are contagious 10 to 14 days before
symptoms occur.
- HAV is released in stool in high
concentrations and is spread via fecal-oral
route.
- Spread in contaminated water, in food, and
in dirty hands.
- Raw or improperly treated sewage can taint
the water supply and contaminate shellfish.
9. Hepatitis A: Clinical Syndrome:
- Similar to HBV.
- Immune-mediated damage to the liver.
- Intensify for 4-6 days before the icteric (jaundice) phase.
- Can last up to 2 months.
- Initial symptoms: fever, fatigue, nausea, loss of appetite,
vomiting, and abdominal pain.
- May be accompanied: dark urine (bilirubinuria), pale stool,
and then jaundice, abdominal pain and itch.
- Rare fulminant (high fulminant mortality).
10. Hepatitis A: Laboratory Diagnosis:
- The course of clinical symptoms, identification for known infected source.
- Most important: anti-HAV IgM.
- Virus isolation is not performed.
Treatment, Prevention, Control:
- Interrupt the fecal-oral spread.
- Prophylaxis: immune serum globulin: before or early in incubation period
- Vaccine: killed HAV, recommended for all children < 1 yo.
12. Hepatitis B:
- Previously known as serum hepatitis.
- Spread parenterally by blood or needles, by sexual
contact, and perinatally.
- Incubation period of 3 months.
- After which icteric symptoms start insidiously. Might be followed by chronic
hepatitis.
- Causally associated with primary hepatocellular carcinoma (PHC).
13. - Specifically, the genome is small, circular,
partly double-stranded DNA of 3200 bases.
- Encodes a reverse transcriptase and replicates
through an RNA intermediate.
- Major member of hepadnaviruses.
- Difficult to culture.
- Small enveloped DNA virus with several unusual properties.
14.
15. - The virion includes a protein kinase and a
polymerase with reverse transcriptase and
ribonuclease H activity, as well as a P protein
attached to the genome.
- The virion is surrounded by an icosahedral
capsid formed by the hepatitis B core antigen
(HBcAg) and an envelope containing three
forms of glycoprotein hepatitis B surface
antigen (HBsAg).
16. - HBsAg-containing particles are released into the
serum, outnumber the actual virions. Has two
forms: spherical, filamentous.
- These particles serve as antigen decoy particles.
17. Hepatitis B: Replication:
- Attachment by HBsAg.
- Nucleocapsid delivers the genome to the
nucleus.
- The partial DNA strand becomes complete to
form completed double-stranded DNA circle.
- Many points to start transcription on DNA
resulting in three classes of mRNA causing
sometimes shedding of the HBe and
incorporation of HBc into the virion.
18. Hepatitis B: Pathogenesis and Immunity:
- HBV can cause acute or chronic, symptomatic or
asymptomatic disease determined by person’s
immune response.
- HBV found majorly in blood (most effective
infection), but also in semen, saliva, milk, vaginal
and menstrual secretions, and amniotic fluid.
- The virus starts replication after three days of
acquisition, symptoms may not be observed for
45 days or longer because they are primarily
caused by immunopathology.
19. Hepatitis B: Epidemiology:
- In the world one out of three people have been infected with HBV.
- Chronic HBV infection > 350 million people.
- Transmission through contaminated blood and through very close personal contact involving
the exchange of semen, saliva, and vaginal secretions.
- Importance of blood screening.
- 1-2 million deaths per year.
- It’s decreasing due to vaccines.
20. Hepatitis B: Clinical Syndrome:
Acute infection:
- Less symptomatic or asymptomatic in children.
- Long incubation, insidious onset.
- Prodromal period: fever, malaise, anorexia.
- Followed by: nausea, vomiting, abdominal discomfort, and chills.
- Soon thereafter: the classic icteric symptoms: (e.g., jaundice, dark
urine, pale stool).
- May promote hypersensitivity reactions caused by immune
complexes of HBsAg and antibody.
21. Chronic infection:
- 5-10% of cases.
- Usually after mild or inapparent initial disease.
- One third of those people have chronic active
hepatitis (continues destruction and causes
scarring of the liver, cirrhosis, liver failure, or
PHC).
- The other two third have chronic passive
hepatitis.
22. PHC (primary Hepatocellular Carcinoma):
Hepatic carcinoma, primary. Large multifocal hepatocellular carcinoma (HCC) in an 80-
year-old man without cirrhosis.
23. Hepatitis B: Laboratory Diagnosis:
- The initial diagnosis can be made on basis of the clinical symptoms and the presence of liver
enzymes in blood.
- Serology describes the course and the nature of the disease.
24. - IgM anti-HBc is the best way to diagnose a recent acute infection.
- The amount of virus in blood: determined by quantitative genome assays using PCR.
25. Hepatitis B: Treatment, prevention, and control:
- Hepatitis B immune globulin may be administered
within a week of exposure.
- Chronic infection treatment: drugs targeted at the
polymerase or the nucleosides analogs for a year.
- Prevention: screening blood, safe sex, avoiding some
lifestyles, wearing gloves in hospitals....
- Vaccination: recommended for infants, children, and
high risk groups of people, a series of three
injections.
27. Hepatitis C: Structure, replication, and pathogenesis:
- The only member of the Hepacivirus genus of the Flaviviridae family.
- 6 genotypes. Positive-sense RNA genome, enveloped.
- Viral RNA-dependent RNA polymerase (gives antigen variability).
- The ability of HCV to remain cell associated and prevent host cell death promotes persistent
infection but results in liver disease later in life.
- Virus particles can be produced in chronically infected, potentially asymptomatic individuals.
- As for HBV, once established, the chronic infection can exhaust CD8 cytotoxic T cells so they
cannot resolve the infection.
- It’s suggested that HCV may predispose the development of PHC.
28. Hepatitis C: Epidemiology:
- HCV is transmitted primarily in infected blood and sexually.
- Almost every HIV-infected people are HCV-infected too.
- The high incidence of chronic asymptomatic infections
promotes the spread.
Clinical Syndrome:
- Acute Hepatitis ends with recovery.
- Severe rapid progression to cirrhosis.
- Chronic persistence often progresses to chronic
active hepatitis.
29. Hepatitis C:
- Laboratory diagnosis: based on ELISA recognition of anti-HCV antibody or detection
of the RNA genome. Antibody is not always detectable: the gold standard for
confirming diagnosis and following antiviral therapy:
Genome detection and quantitation by RT-PCR, branched-chain DNA, and related
techniques.
- Drugs: recombinant interferon-⍺ or pegylated interferon, alone or with ribavirin -
boceprevir - telaprevir - ledipasvir - sofosbuvir.
- Precautions for preventing HCV are similar for HBV.
31. Hepatitis G:
- Resembles HCV in many ways.
- Flavivirus. Transmitted in blood, and has a predilection for chronic hepatitis
infection.
- It is identified by detection of the genome by RT-PCR or other RNA detection
methods.
33. Hepatitis D:
- Single-stranded RNA, circular, forms a rod shape as a result of its extensive base
pairing.
- Uses HBV and targeted cell to replicate and produce its protein.
- HBsAg is essential for packaging the virus.
- 40% of fulminant hepatitis infections.
35. Hepatitis E:
- Spreads by fecal-oral route. Especially in contaminated water.
- Calicivirus, RNA genome, naked capsid.
- More problematic in developing countries.
- Symptoms are similar to HAV, causes only acute disease.
- Infection is serious in pregnant women (mortality of 20%).