Hepatitis Viruses

Hepatitis

• inflammation of the liver

How long does acute hepatitis last

• resolves within 6 months

How long does chronic hepatitis last

• > 6 months 

  • involves carriers

  • cirrhosis, liver failure, or liver cancer

What symptoms are associated with Hepatitis

• fatigue

• headaches

• anorexia

• fever

• N/V

• hepatomegaly 

• abdominal pain 

• jaundice

• dark colored urine

Primary Hepatitis

• involves the liver without affecting other organ systems

what complications are associated with primary hepatitis

• cirrhosis

• liver failure

• hepatocellular carcinoma

80% of cases caused by hepatitis viruses are associated with 

• primary hepatitis 

How are hepatitis viruses related

• by their tissue tropism

  • not genome or structure

Hepatitis B geonome

• DNA

Hepatitis A, C-E genome

• RNA

Secondary Hepatitis

• secondary infection of the liver following disseminated infection 

examples of secondary hepatitis

• Epstein-Barr Virus (EBV)

• Cytomegalovirus (CMV)

• varicella-zoster virus (VZV)

Direct Liver Injury

• substance causes damage to hepatocytes 

• associated with medications or toxins 

What are different liver funtion tests (LFTs)

• aspartate aminotransferase (AST)

• alanine aminotransferase (ALT) 

Indirect Liver Disease

• immune response to virus, toxins, medications

• innate response: NK cells, IFN

• adaptive response: T cells

liver function test results of indirect liver disease

• AST and ALT rise gradually 

liver function test results of direct liver disease

• AST and ALT increase rapidly

what is the genome of hepatitis B?

• dsDNA

does hepatitis D have a carrier state? 

• yes, with HBV

can chronic hepatitis occur with hepatitis D

• yes, with HBV

Hepatitis B virus

• Hepadnaviridae 

• DNA virus 

• enveloped 

• isohedral nucleocapsid

Hepatitis B virus Genome

• circular

  • one strand is full length 

  • one strand is incomplete

HBV DNA polymerase

• can use both DNA and RNA as a template

  • use reverse transcriptase activity 

What are the different parts of HBV

• HBsAg

• HBcAg

• HBeAg

Hepatitis B surface antigen

• HbsAg

• envelope protein 

Hepatitis B core antigen

• HBcAg

• nucleocapsid protein

Hepatitis B envelope antigen

• HBeAg 

  • soluble antigen 

  • found between nucleocapsid and envelope

How is HBV transmitted

• parenteral

  • bloodborne pathogen

  • found in blood, body fluids, breast milk

• sexual contact

• vertical transmission

What are high risk groups for HBV

• IV drug users

• having many sex partners

• MSM

• tattoos or body piercing 

• healthcare

• people undergoing hemodialysis

• infants born to HBV-positive mothers 

Incubation period of HBV

• approx 90 days

• travels via blood to liver and infects hepatocytes 

• immune response slowly clears infection 

Asymptomatic Infection of HBV

• most frequent 

• minimal CPE is produced and minimal inflammation 

• weak response- kids

• robust response-adults 

how can HBV cause damage to host?

• cause antibody hypersensitivity reactions

  • HBsAg and anti-HBs antibody immune complexes form 

  • can cause vasculitis, arthralgia, glomerulonephritis

Acute,self limited hepatitis B

• 20-30% adults

• result in complete resolution

chronic infection pf HBV

• 90% of infants 

• 25-50% children1-5

• 5-10% adults 

what are the two major complications that could arise from hepatitis B?

• cirrhosis

• hepatocellular carcinoma 

Cirrhosis

• fibrosis/scarring of liver tissue

Hepatocellular carcinoma

• poor prognosis and most likely fatal 

• cause approx 80% of cases worldwide 

What liver enzymes are elivated in HBV?

• ALT and AST

what method is used to diagnose HBV

• HBV serologic  testing 

when conducting a serologic evaluation, what will be positive for an acute HBV infection?

• HBsAg

  • first detectable serologic marker

What is the first antibody in acute hepatitis?

• anti-HBc IgM

  • positive after HBsAg is detected 

  • persists weeks after HBsAg is no longer detectable

Core Window of HBV

• HBsAg is no longer detectable 

• anti-HBs not yet detectable 

what is happening during the core window of HBV

• anti-HBc is the sole marker for acute hepatitis B

  • becomes undetectable within 3-6 m 

  • anti-HBc IgG becomes detectable around 4-6 m and can persist for decades  

HBeAg

• hepatitis B envelope antigen 

• nonstructural nucleocapsid protein 

what is the marker of HBV replication and high infectivity? 

• HBeAg

  • disappears before HBsAg

what is present in all chronic HBV infections?

• anti-HBc IgG

what is detected in the early phase of chronic HBV infections? 

• HBeAg 

  • can remain for years 

What is detected indefinitely in chronic HBV

• HBsAg

What is not detected in chronic HBV?

• detectable antibodies

  • Anti-HBs to HBsAg

what indicates lower infectivity of a patent in chronic HBV? 

• anti-HBe 

HBV Resolved/Past infections should be positive for what?

• anti-HBs

• anti-HBc

HBV Acute infections should be positive for what?

• HBsAg

• Anti-HBc IgG

• HBeAg

HBV chronic infections with high infectivity should be positive for what?

• HBsAg

• Anti-HBc IgG

HBV chronic infections with low infectivity should be positive for what?

• HBsAg

• Anti-HBc IgG

• Anti-HBe

HBV vaccinated individuals should be positive for what?

• anti-HBs 

How do you prevent getting HBV

• screen pregnant women and vaccinate newborns

• interview and screen blood donors

• antivirals 

• liver transplantation 

• recombinant vaccines against HBV

Hepatitis D virus

• known as delta hepatitis 

• only infects patients with HBV infections

What is required for the hepatitis D virus?

• requires HBV for replication

defective ssRNA HDV virus needs what?

• HBV HBsAg for its envelope 

how is HDV transmitted

• parenteral 

• sexual contact 

• vertical transmission 

HDV coinfection

• HBV and HDV acquired simultaneously

• self-limiting mild to severe infections

HDV Superinfection

• HDV acquired during chronic HBV infection

• rapidly accelerates chronic HBV 

What antibodies are looked for when diagnosing HDV?

• anti-HDV IgM

• anti-HDV total (IgM and IgG)

what indicates and HDV coinfection?

• Positive HBsAg

• Positive anti-HBc IgM

• Positive anti-HDV

how does one prevent HDV?

• Hepatitis B vaccination 

Hepatitis A Virus (HAV)

• non-enveloped, icosahedral ssRNA 

  • Picornavirus 

• single stereotype 

How is HAV transmitted

• fecal-oral route 

HAV does not have what?

• chronic infections

pathogenesis of HAV

• replication in hepatocytes

• all are resolved in acute phase 

How is HAV diagnosed

• Anti-HAV IgM 

• Anti-HAV total 

• HAV RNA PCR

How is HAV prevented

• boil contaminated water

• properly cook food

• wash hands 

• vaccines 

Hepatitis C virus

• enveloped ssRNA virus

• no homology with other hepatitis viruses

what is the leading cause for a liver transplant in the US?

• chronic HCV

How is HCV transmitted 

• parenteral

• sexual contact

• vertical transmission

Anti-HCV screening 

• occurs 8-12 weeks after exposure

• may be delayed in immunocompromised individuals 

what test is used to confirm anti-HCV screening

• HCV RNA NAT

NAT

• confirmatory test- HCV RNA detection 

  • confirms curren infection 

viral load testing for Hepatitis C

• does not correspond to severity

• measures response to treatment 

if while testing for HCV, what happens if test is negative

• nonreactive

• no HCV antibody detected 

• stop testing 

if while testing for HCV, what happens if test is positive

• reactive 

• conduct HCV RNA test 

  • +

    • detected/current infection 

  • -

    • no current infection

    • need additional testing 

HCV genotyping assays

• recommended for

  • patients with cirrhosis

  • previous unsuccessful hepatitis C treatment 

How do you prevent/treat Hepatitis C

• screen blood for HCV

• direct acting antivirals 

• liver transplant

Hepatitis E virus

• non enveloped ssRNA

• Hepeviridae 

• four genotypes 

how is hepatitis E transmitted

• fecal oral route 

when pregnant women contract hepatitis E, what could happen? 

• rare cases of fulflment hepatitis can occur

How is HEV diagnosed

• Anti-HEV IgM (acute)

• Anti-HEV IgG (covalence)

• HEV RNA PCR

How is HEV prevented

• boil water

• cook foods

• supportive therapy 

• no available vaccine