Class 10 - Hepatitis Viruses: Ann Machablishvili, MD, PHD

Class 10 - Hepatitis viruses
Ann Machablishvili, MD, PhD
Head of Influenza and respiratory viruses laboratory

Class 10 study topics - Hepatitis viruses
E
A
C
Hepatitis A virus (HAV)
➢ Hepatitis A
• Picornavirus
• Naked nucleocapsid
• A single stranded, positive-polarity RNA
• No virion polymerase
• A single serotype
• Transmission
✓Fecal-oral
✓Blood-borne - uncommon (brief viremia, low titer)
Pathogenesis and clinical findings
Hepatocellular injury by
replicates in the
spreads to the liver immune attack -
GI tract
cytotoxic T cells
• No cytopathic for the hepatocyte

• Incubation period – 2 - 4 weeks
• Most infections - asymptomatic
• Lifelong immunity
Laboratory Diagnosis, Treatment & Prevention
• IgM antibody detection
• PCR
• No specific drug
• Vaccine – killed virus
• Immune globulin during the incubation
period can mitigate the disease

Hepatitis E virus (HEV)
➢ Hepatitis
• Naked, single-stranded positive-polarity RNA
• Transmitted by fecal–oral route
• No chronic carrier state
• No cirrhosis
• No hepatocellular carcinoma
• Serology - IgM detection in serum
• PCR - RNA detection
• No antiviral therapy
• No vaccine
Hepatitis B virus (HBV)
➢ Hepatitis B
➢ Hepatocellular carcinoma
In 2019 - 820 000 deaths, mostly from cirrhosis and hepatocellular carcinoma
• Hepadnavirus, enveloped, icosahedral

• Incomplete circular double-stranded DNA
➢ One strand - one-third missing
➢ Other strand - “nicked” (not covalently bonded)
• DNA polymerase in virion - a reverse transcriptase
for the synthesis of progeny genome DNA
HBV antigens
• HBsAg (the surface antigen) - important for laboratory diagnosis and immunization
• HBcAg (the core antigen) - the nucleocapsid protein
• HBeAg (the e antigen) – soluble, released by infected cells indicator of transmutability
• HBx antigen - inactivates p53 tumor suppressor protein (leads to hepatocellular carcinoma)
HBV classification
• For vaccine purposes - HBV has one serotype based on HBsAg
• 2 separate systems
➢ Serologic subtype – 9 based on the heterogeneity of HBsAg
➢ Genotype - 10 designated A through J
HBV serotypes and genotypes vary geographically

Transmission
Humans are the only natural hosts

➢ Blood
➢ During birth to child (rare transplacental)
➢ Sexual contact
• Hepatocellular injury - due to immune attack by cytotoxic (CD8) T cells
inflammation and necrosis
• Antigen–antibody complexes - arthritis, rash, glomerulonephritis
• Chronic carrier state - in 5% of adults

in 90% of neonates (poor cytotoxic T-cell activity)
• Incubation period – 10-12 weeks
• Chronic hepatitis, cirrhosis, hepatocellular carcinoma
➢Hepatocellular carcinoma - the integration of part of the viral DNA into hepatocyte DNA
and subsequent synthesis of HBx protein
Laboratory Diagnosis
• Serologic testing
➢ Surface antigen (HBsAg) - >6 months indicates a chronic carrier state
➢ Surface antibody (HBsAb)
➢ Core antibody (HBcAb)
➢ e antigen - a chronic carrier who is making infectious virus
The “window” phase - neither detectable HBs antigen nor HBs antibody
• PCR
• Rapid tests
Treatment
• Acute - no treatment required
• Chronic - a reverse transcriptase inhibitor nucleoside analogues
Tenofovir or Entecavir - reduce the inflammation
but does not cure the carrier state
• A combination of Tenofovir + Emtricitabine - also effective
Prevention
• Vaccine - HBsAg as the immunogen
• Hyperimmune globulins - obtained from donors with high titers of HBsAb
• Education of chronic carriers
• Passive-active immunization to prevent infection
➢Neonates
➢Needle-stick injuries
Breast feeding of immunized neonates by mothers who are chronic carriers - little risk of infection
Hepatitis C virus (HCV)
➢ Hepatitis C
➢ Hepatocellular carcinoma
In 2019 - 290 000 deaths, mostly from cirrhosis and hepatocellular carcinoma
• Flavivirus
• Enveloped, single stranded RNA
• Positive-polarity RNA
• No polymerase in virion
• Multiple serotypes
Transmission
➢Blood
➢During birth to child (rare transplacental)
➢Sexual contact – less common

• Hepatocellular injury - due to cytotoxic T cells
• HCV replication does not kill cells
• >50% of chronic carrier state hepatitis and hepatocellular carcinoma
Laboratory Diagnosis
• Rapid tests
• Serology - antibody detection
• PCR - “viral load” to evaluate active infection

Treatment
• Acute - pegylated interferon alpha, antivirals usually not prescribed
• Chronic - a combination of 3 class drugs
➢ RNA polymerase inhibitor (Sofosbuvir)
➢ NS5A inhibitor (Ledipasvir)
➢ Protease inhibitor (Paritaprevir)
Prevention
• No vaccine
• Discard donor blood if positive on HCV antibody
• No hyperimmune globulins
Hepatitis D virus (HDV)
➢ Hepatitis D (hepatitis delta)
• Defective virus - uses hepatitis B surface antigen as its protein coat
• Can replicate only in cells already infected with HBV ( a helper virus)
• One piece of single-stranded, negative-polarity, circular RNA
• No polymerase in virion
• One serotype
• Transmission - blood, sexually, from mother to child
• Hepatocellular injury probably caused by cytotoxic T cells
• Chronic hepatitis and chronic carrier state occur
• Serologic testing – antigen or antibody detection
• Pegylated alpha interferon to mitigate symptoms - no eradication of carrier state
• HBV vaccine and hyperimmune globulins - prevent HDV infection as well
Homework
Warren Levinson, Review of Medical Microbiology and

Immunology 14th edition. 2016
Chapters 41 (pp. 342-353)

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Class 10 - Hepatitis viruses

Ann Machablishvili, MD, PhD

Head of Influenza and respiratory viruses laboratory

• No cytopathic for the hepatocyte

• IgM antibody detection

• Vaccine – killed virus

• Immune globulin during the incubation

period can mitigate the disease

• Hepadnavirus, enveloped, icosahedral

• For vaccine purposes - HBV has one serotype based on HBsAg

HBV serotypes and genotypes vary geographically

Humans are the only natural hosts

inflammation and necrosis

• Antigen–antibody complexes - arthritis, rash, glomerulonephritis

• Chronic carrier state - in 5% of adults

• Enveloped, single stranded RNA

➢During birth to child (rare transplacental)

➢Sexual contact – less common

• Serology - antibody detection

• PCR - “viral load” to evaluate active infection

Warren Levinson, Review of Medical Microbiology and

Chapters 41 (pp. 342-353)

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