virology of hepatitis
DESCRIPTION
by: Wan Athirah bt Wan Abd HalimTRANSCRIPT
Hepatitis A Virus
• Picornaviridae family• One serotype- stable(protective for life)• Non-enveloped• Single stranded positive• Stable ( ether, acid, heat: 60 c for 1 hr)• Destroyed (autoclaving, boil 5 min, chlorine)
• Feco-oral route• Crowded: early age, high sanitation: older
• Clinical finding• IP: 3-4 weeks• Asymptomatic in children• Life long immunity• No chronicity
Lab investigation
• Detect HAV antibodies- IgM: acute phase (most reliable)- IgG: life long protection• Detect HAV antigen in stool (ELISA)• Detect HAV RNA in stool (PCR, nucleic acid
hybridization)
Prevention and control
• Control food and water• Good hygiene-hand refreshing• Chlorine and proper sewage• Active immunization• Passive immunization
Hepatitis E virus
• Unclassified genus• Feco-oral route, water borne• Endemic in tropical countries• IP: 40 days• HIGH MORTALITY RATE IN PREGNANT WOMAN• No chronicity• Detect anti HEV antibodies and HEV-RNA in serum• Same prevention and control as hepatitis A
Hepatitis B virus
• Hepadnavirus• Icosahendral nucleocapsid• Partially double-stranded circular DNA genome• Outer shell: HBsAg• Inner core: Hbc Ag• Secreted in soluble form: HBeAg• EM of serum: spherical particles, filamentous
particles and complete virions (Dane particle)
Epidemiology and transmission
• High titre are present in blood and serum1. Percutaneous• Blood transfusion• Contaminated syringes and needles• Improperly sterilized instrument• Razor and tooth brush sharing• Needle stick injuries2. Sexual transmission3. Perinatal transmission
Clinical features
• IP: 10-12 weeks• Many asymptomatic• Outcome:• Adult: 90-95% recover completely• Infected infant: chronic carries• Chronic: can lead to cirrhosis, liver failure and
death• CHRONIC: HIGH RISK OF HCC • HBV Vaccine
Virologic and serologic events
• First appearance: HBs Ag• Viremic stage: HBV DNA and HBE Ag• HBsAg , appears 2-6 weeks before clinical and
biochemical evidence, throughout the course, disappearr by 6 months after exposure
• Viral replication: IgM specific anti HBc• Window phase: disappearance of Hbs Ag. After
that, antibody to HbsAg is detected• Start of resolution of disease: anti Hbe
Acute phase with recovery
• HBV chronic carriers: Hbs Ag persists for more than 6 months in thepresence of HbeAg or anti-Hbe.
• Low titres of IgM anti-Hbc are found in the sera of most chronic carriers.
• Lab:• ELISA: HBV antigen and antibodies• PCR: HBV DNA
Interpretation of the result
1. serologic: four phase of HBV infection2. Immunization: anti-Hbs3. Transmissibility: HbeAg4. Infectious virion present: Viral DNA
Test acute phase
Window phase
Complete recovery
Chronic carrier state
HBs Ag Positive Negative Negative Positive
Anti-Hbs Negative Negative Positive Negative
Anti-Hbc Positive Positive Positive Positive
Prevention and control
1. Hepatitis B vaccine- Prevent consequence- Dose: 0,1,6- Plasma derived HBs Ag- All infant, health care personnel, on transfusion,
dialysis2. Hepatitis B immunoglobulin (simultenously)- Soon after exposure- Infants to HBV positive mother, exposed person
Hepatitis D virus
• Defective virus, uses Hbs Ag as envelope (HBV is helper virus)
• Blood borne virusTwo types:• Coinfection: both at same time• Superinfection: of chronically infected HBV
Outcome:• Coinfected: more severe that HBV alone, but
incidence of chronic hepatitis is about the same
• Superinfected: much more severe, higher incidence of chronic hepatitis
Lab:• ELISA: HD Ag, IgM and anti HD antibodies• PCR: HD-RNA
Hepatitis C vaccine
• Flaviviridae• 6 genotypes, not correlated with clinical
disease, differ in response to antiviral therepy.• Egypt: 4a• Percutaneous or permucosal
• Appearance of anti-HCV antibodies: 8-9 weeks• HCV RNA: 1-3 weeks after exposure. The
means of diagnosis in seronegative patients• Chronic hepatitis: serum ALT fluctuate
overtime and maybe intermittently normal. HCV RNA may persists for decades
• Outcome: 70-90% chronic HCV infection• Resembles hepatitis B as regards
predisposition to chronic liver disease, cirrhosis and HCC.
• End stage liver disease associated with HCV is most common indication for liver transplantation.
Lab diagnosis
1. ELISA: detect antibodies to HCV, consider:- Early seronegative phase: negative result- Positive: acute, chronic, resolved?- False positive can occur. Confirmed by : RIBA.
If positive, test for viral RNA for active disease.
- Poor serologic response in some patient. Test for HCV RNA.
2. RT-PCR, for derection of HCV RNA- Active disease- Early seronegative- Poor serologic patients
• Acute self limiting: dissappear (resolved)• Measure viral load: response to antiviral
therapy (quantitative PCR)
Hepatitis
• Diffuse inflammation of parenchyma• Causes: • Infective• Metabolic• Autoimmune• Chemicals• drugs
1.Hepatotropic- most common form - A, B, C, D, E, G2. Systemic
Clinicopathological syndromes
1. Subclinical – asymptomatic, any type2. Acute viral hepatitis – any type3. Chronic viral hepatitis – HBV, HCV, HDV.
NEVER HAV and HEV4. Carrier state – mainly HBV. NEVER HAV, HEV5. Fulminant hepatitis – HEV among pregnant
females
Clinical course of acute hepatitis
1. HAV - Most undergo complete recovery2. HBV- Most (>90%) complete recovery- 1-2% chronic hepatitis3. HCV- >70% progress to chronic hepatitis- <30% undergo recovery- Few develop fulminant
4. HDV- coinfection: • 90% undergo recovery• 3-4% develop fulminat• Rare progress to chronic hepatitis- Superinfection• 10-15%: recovery• 80%: chronic hepatitis• 7-10%: fulminant5. HEV- Most undergo complete recovery- Pregnant females: fulminant (20%)- No chronic or carrier state
CHRONIC VIRAL HEPATITIS
• Symptomatic, biochemical, serological evidence of inflammatory hepatic disease with histologically documented without improvement, more than 6 months
• Mainly: HCV >70%, HDV (80% superinfection) and some HBV
CARRIER STATE
• Not manifest symptoms, but persistent antigenemia(circulating infectious virus particles), more than 6 months with normal transaminases and no clinical symptoms.
• Mainly: HBV (adults infected by HBV and non-immunized infants born to infected mother)
• Increased risk of HCC