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